Skip to main content

Advertisement

SpringerLink
Log in

Induction of intestinal lymphoid tissue formation by intrinsic and extrinsic signals

  • Review
  • Published:
Seminars in Immunopathology Aims and scope Submit manuscript

Abstract

Since the discovery of inducer cells as a separate lineage for organogenesis of Peyer’s patches in the small intestine of fetal mice, a lot of progress has been made in understanding the molecular pathways involved in the generation of lymphoid tissue and the maintenance of the lymphoid architecture. The findings that inducer cells also exist in adult mice and in humans, have a lineage relationship to natural killer cells, and can be stimulated during infections highlight their possible role in establishing innate and adaptive immune responses. Novel concepts in the development of intestinal lymphoid tissues have been made in the past few years suggesting that lymphoid organs are more plastic as previously thought and depend on antigenic stimulation. In addition, the generation of novel lymphoid organs in the gut under inflammatory conditions indicates a function in chronic diseases. The present review summarizes current knowledge on the basic framework of signals required for developing lymphoid tissue under normal and inflammatory conditions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Brandtzaeg P, Pabst R (2004) Let's go mucosal: communication on slippery ground. Trends Immunol 25:570–577. doi:10.1016/j.it.2004.09.005

    Article  CAS  PubMed  Google Scholar 

  2. Bouskra D, Brezillon C, Berard M, Werts C, Varona R, Boneca IG, Eberl G (2008) Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis. Nature 456:507–510. doi:10.1038/nature07450

    Article  CAS  PubMed  Google Scholar 

  3. Pabst O, Herbrand H, Friedrichsen M, Velaga S, Dorsch M, Berhardt G, Worbs T, Macpherson AJ, Forster R (2006) Adaptation of solitary intestinal lymphoid tissue in response to microbiota and chemokine receptor CCR7 signaling. J Immunol 177:6824–6832

    CAS  PubMed  Google Scholar 

  4. Tsuji M, Suzuki K, Kitamura H, Maruya M, Kinoshita K, Ivanov II, Itoh K, Littman DR, Fagarasan S (2008) Requirement for lymphoid tissue-inducer cells in isolated follicle formation and T cell-independent immunoglobulin a generation in the gut. Immunity 29:261–271. doi:10.1016/j.immuni.2008.05.014

    Article  CAS  PubMed  Google Scholar 

  5. Mebius RE (2003) Organogenesis of lymphoid tissues. Nat Rev Immunol 3:292–303. doi:10.1038/nri1054

    Article  CAS  PubMed  Google Scholar 

  6. Nishikawa S, Honda K, Vieira P, Yoshida H (2003) Organogenesis of peripheral lymphoid organs. Immunol Rev 195:72–80. doi:10.1034/j.1600-065X.2003.00063.x

    Article  CAS  PubMed  Google Scholar 

  7. Aloisi F, Pujol-Borrell R (2006) Lymphoid neogenesis in chronic inflammatory diseases. Nat Rev Immunol 6:205–217. doi:10.1038/nri1786

    Article  CAS  PubMed  Google Scholar 

  8. Drayton DL, Liao S, Mounzer RH, Ruddle NH (2006) Lymphoid organ development: from ontogeny to neogenesis. Nat Immunol 7:344–353. doi:10.1038/ni1330

    Article  CAS  PubMed  Google Scholar 

  9. Spencer J, MacDonald TT, Finn T, Isaacson PG (1986) The development of gut associated lymphoid tissue in the terminal ileum of fetal human intestine. Clin Exp Immunol 64:536–543

    CAS  PubMed  Google Scholar 

  10. Cornes JS (1965) Peyer's patches in the human gut. Proc R Soc Med 58:716

    CAS  PubMed  Google Scholar 

  11. Mutwiri G, Watts T, Lew L, Beskorwayne T, Papp Z, Baca-Estrada ME, Griebel P (1999) Ileal and jejunal Peyer's patches play distinct roles in mucosal immunity of sheep. Immunology 97:455–461. doi:10.1046/j.1365-2567.1999.00791.x

    Article  CAS  PubMed  Google Scholar 

  12. Pabst R, Reynolds JD (1987) Peyer's patches export lymphocytes throughout the lymphoid system in sheep. J Immunol 139:3981–3985

    CAS  PubMed  Google Scholar 

  13. Yasuda M, Nasu T, Murakami T (2009) Differential cytokine mRNA expression in single lymphatic follicles of the calf ileal and jejunal Peyer's patches. Dev Comp Immunol 33:430–433. doi:10.1016/j.dci.2008.09.007

    Article  CAS  PubMed  Google Scholar 

  14. Crabbe PA, Nash DR, Bazin H, Eyssen H, Heremans JF (1970) Observations on lymphoid tissues from conventional and germ free mice. Lab Invest 22:448

    CAS  PubMed  Google Scholar 

  15. Iwasaki A, Kelsall BL (2000) Localization of distinct Peyer's patch dendritic cell subsets and their recruitment by chemokines macrophage inflammatory protein (MIP)-3alpha, MIP-3beta, and secondary lymphoid organ chemokine. J Exp Med 191:1381–1394. doi:10.1084/jem.191.8.1381

    Article  CAS  PubMed  Google Scholar 

  16. Salazar-Gonzalez RM, Niess JH, Zammit DJ, Ravindran R, Srinivasan A, Maxwell JR, Stoklasek T, Yadav R, Williams IR, Gu X, McCormick BA, Pazos MA, Vella AT, Lefrancois L, Reinecker HC, McSorley SJ (2006) CCR6-mediated dendritic cell activation of pathogen-specific T cells in Peyer's patches. Immunity 24:623–632. doi:10.1016/j.immuni.2006.02.015

    Article  CAS  PubMed  Google Scholar 

  17. Iwasaki A, Kelsall BL (2001) Unique functions of CD11b+, CD8 alpha+, and double-negative Peyer's patch dendritic cells. J Immunol 166:4884–4890

    CAS  PubMed  Google Scholar 

  18. Yamanaka T, Helgeland L, Farstad IN, Fukushima H, Midtvedt T, Brandtzaeg P (2003) Microbial colonization drives lymphocyte accumulation and differentiation in the follicle-associated epithelium of Peyer's patches. J Immunol 170:816–822

    CAS  PubMed  Google Scholar 

  19. Tsuji M, Komatsu N, Kawamoto S, Suzuki K, Kanagawa O, Honjo T, Hori S, Fagarasan S (2009) Preferential generation of follicular B helper T cells from Foxp3+ T cells in gut Peyer's patches. Science 323:1488–1492. doi:10.1126/science.1169152

    Article  CAS  PubMed  Google Scholar 

  20. Cerutti A, Rescigno M (2008) The biology of intestinal immunoglobulin A responses. Immunity 28:740–750. doi:10.1016/j.immuni.2008.05.001

    Article  CAS  PubMed  Google Scholar 

  21. Hamada H, Hiroi T, Nishiyama Y, Takahashi H, Masunaga Y, Hachimura S, Kaminogawa S, Takahashi-Iwanaga H, Iwanaga T, Kiyono H, Yamamoto H, Ishikawa H (2002) Identification of multiple isolated lymphoid follicles on the antimesenteric wall of the mouse small intestine. J Immunol 168:57–64

    CAS  PubMed  Google Scholar 

  22. Lorenz RG, Chaplin DD, McDonald KG, McDonough JS, Newberry RD (2003) Isolated lymphoid follicle formation is inducible and dependent upon lymphotoxin-sufficient B lymphocytes, lymphotoxin beta receptor, and TNF receptor I function. J Immunol 170:5475–5482

    CAS  PubMed  Google Scholar 

  23. Ivanov II, Diehl GE, Littman DR (2006) Lymphoid tissue inducer cells in intestinal immunity. Curr Top Microbiol Immunol 308:59–82. doi:10.1007/3-540-30657-9_3

    Article  CAS  PubMed  Google Scholar 

  24. Glaysher BR, Mabbott NA (2007) Isolated lymphoid follicle maturation induces the development of follicular dendritic cells. Immunology 120:336–344. doi:10.1111/j.1365-2567.2006.02508.x

    Article  CAS  PubMed  Google Scholar 

  25. Lorenz RG, Newberry RD (2004) Isolated lymphoid follicles can function as sites for induction of mucosal immune responses. Ann N Y Acad Sci 1029:44–57. doi:10.1196/annals.1309.006

    Article  CAS  PubMed  Google Scholar 

  26. Kanamori Y, Ishimaru K, Nanno M, Maki K, Ikuta K, Nariuchi H, Ishikawa H (1996) Identification of novel lymphoid tissues in murine intestinal mucosa where clusters of c-kit + IL-7R + Thy1+ lympho-hemopoietic progenitors develop. J Exp Med 184:1449–1459. doi:10.1084/jem.184.4.1449

    Article  CAS  PubMed  Google Scholar 

  27. Pabst O, Herbrand H, Worbs T, Friedrichsen M, Yan S, Hoffmann MW, Korner H, Bernhardt G, Pabst R, Forster R (2005) Cryptopatches and isolated lymphoid follicles: dynamic lymphoid tissues dispensable for the generation of intraepithelial lymphocytes. Eur J Immunol 35:98–107. doi:10.1002/eji.200425432

    Article  CAS  PubMed  Google Scholar 

  28. Kraehenbuhl JP, Neutra MR (2000) Epithelial M cells: differentiation and function. Annu Rev Cell Dev Biol 16:301–332. doi:10.1146/annurev.cellbio.16.1.301

    Article  CAS  PubMed  Google Scholar 

  29. Sierro F, Pringault E, Assman PS, Kraehenbuhl JP, Debard N (2000) Transient expression of M-cell phenotype by enterocyte-like cells of the follicle-associated epithelium of mouse Peyer's patches. Gastroenterology 119:734–743. doi:10.1053/gast.2000.16481

    Article  CAS  PubMed  Google Scholar 

  30. Gebert A, Rothkotter HJ, Pabst R (1996) M cells in Peyer's patches of the intestine. Int Rev Cytol 167:91–159. doi:10.1016/S0074-7696(08)61346-7

    Article  CAS  PubMed  Google Scholar 

  31. Fotopoulos G, Harari A, Michetti P, Trono D, Pantaleo G, Kraehenbuhl JP (2002) Transepithelial transport of HIV-1 by M cells is receptor-mediated. Proc Natl Acad Sci U S A 99:9410–9414. doi:10.1073/pnas.142586899

    Article  CAS  PubMed  Google Scholar 

  32. Tyrer PC, Ruth Foxwell A, Kyd JM, Otczyk DC, Cripps AW (2007) Receptor mediated targeting of M-cells. Vaccine 25:3204–3209. doi:10.1016/j.vaccine.2007.01.028

    Article  CAS  PubMed  Google Scholar 

  33. Chabot S, Wagner JS, Farrant S, Neutra MR (2006) TLRs regulate the gatekeeping functions of the intestinal follicle-associated epithelium. J Immunol 176:4275–4283

    CAS  PubMed  Google Scholar 

  34. Gebert A, Steinmetz I, Fassbender S, Wendlandt KH (2004) Antigen transport into Peyer's patches: increased uptake by constant numbers of M cells. Am J Pathol 164:65–72

    PubMed  Google Scholar 

  35. Man AL, Prieto-Garcia ME, Nicoletti C (2004) Improving M cell mediated transport across mucosal barriers: do certain bacteria hold the keys? Immunology 113:15–22. doi:10.1111/j.1365-2567.2004.01964.x

    Article  CAS  PubMed  Google Scholar 

  36. Mora JR, Iwata M, Eksteen B, Song SY, Junt T, Senman B, Otipoby KL, Yokota A, Takeuchi H, Ricciardi-Castagnoli P, Rajewsky K, Adams DH, von Andrian UH (2006) Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells. Science 314:1157–1160. doi:10.1126/science.1132742

    Article  CAS  PubMed  Google Scholar 

  37. Sato A, Hashiguchi M, Toda E, Iwasaki A, Hachimura S, Kaminogawa S (2003) CD11b+ Peyer's patch dendritic cells secrete IL-6 and induce IgA secretion from naive B cells. J Immunol 171:3684–3690

    CAS  PubMed  Google Scholar 

  38. Bjerke K, Brandtzaeg P (1988) Lack of relation between expression of HLA-DR and secretory component (SC) in follicle-associated epithelium of human Peyer's patches. Clin Exp Immunol 71:502–507

    CAS  PubMed  Google Scholar 

  39. Pappo J, Owen RL (1988) Absence of secretory component expression by epithelial cells overlying rabbit gut-associated lymphoid tissue. Gastroenterology 95:1173–1177

    CAS  PubMed  Google Scholar 

  40. Mantis NJ, Cheung MC, Chintalacharuvu KR, Rey J, Corthesy B, Neutra MR (2002) Selective adherence of IgA to murine Peyer's patch M cells: evidence for a novel IgA receptor. J Immunol 169:1844–1851

    CAS  PubMed  Google Scholar 

  41. Kadaoui KA, Corthesy B (2007) Secretory IgA mediates bacterial translocation to dendritic cells in mouse Peyer's patches with restriction to mucosal compartment. J Immunol 179:7751–7757

    CAS  PubMed  Google Scholar 

  42. Anderle P, Rumbo M, Sierro F, Mansourian R, Michetti P, Roberts MA, Kraehenbuhl JP (2005) Novel markers of the human follicle-associated epithelium identified by genomic profiling and microdissection. Gastroenterology 129:321–327. doi:10.1053/j.gastro.2005.03.044

    Article  CAS  PubMed  Google Scholar 

  43. Hase K, Ohshima S, Kawano K, Hashimoto N, Matsumoto K, Saito H, Ohno H (2005) Distinct gene expression profiles characterize cellular phenotypes of follicle-associated epithelium and M cells. DNA Res 12:127–137. doi:10.1093/dnares/12.2.127

    Article  CAS  PubMed  Google Scholar 

  44. Lo D, Tynan W, Dickerson J, Scharf M, Cooper J, Byrne D, Brayden D, Higgins L, Evans C, O'Mahony DJ (2004) Cell culture modeling of specialized tissue: identification of genes expressed specifically by follicle-associated epithelium of Peyer's patch by expression profiling of Caco-2/Raji co-cultures. Int Immunol 16:91–99. doi:10.1093/intimm/dxh011

    Article  CAS  PubMed  Google Scholar 

  45. Pielage JF, Cichon C, Greune L, Hirashima M, Kucharzik T, Schmidt MA (2007) Reversible differentiation of Caco-2 cells reveals galectin-9 as a surface marker molecule for human follicle-associated epithelia and M cell-like cells. Int J Biochem Cell Biol 39:1886–1901. doi:10.1016/j.biocel.2007.05.009

    Article  CAS  PubMed  Google Scholar 

  46. Verbrugghe P, Waelput W, Dieriks B, Waeytens A, Vandesompele J, Cuvelier CA (2006) Murine M cells express annexin V specifically. J Pathol 209:240–249. doi:10.1002/path.1970

    Article  CAS  PubMed  Google Scholar 

  47. Zhao X, Sato A, Dela Cruz CS, Linehan M, Luegering A, Kucharzik T, Shirakawa AK, Marquez G, Farber JM, Williams I, Iwasaki A (2003) CCL9 is secreted by the follicle-associated epithelium and recruits dome region Peyer's patch CD11b+ dendritic cells. J Immunol 171:2797–2803

    CAS  PubMed  Google Scholar 

  48. Finke D, Kraehenbuhl JP (2001) Formation of Peyer's patches. Curr Opin Genet Dev 11:561–567. doi:10.1016/S0959-437X(00)00233-1

    Article  CAS  PubMed  Google Scholar 

  49. Izadpanah A, Dwinell MB, Eckmann L, Varki NM, Kagnoff MF (2001) Regulated MIP-3alpha/CCL20 production by human intestinal epithelium: mechanism for modulating mucosal immunity. Am J Physiol Gastrointest Liver Physiol 280:G710–G719

    CAS  PubMed  Google Scholar 

  50. Kondo T, Takata H, Takiguchi M (2007) Functional expression of chemokine receptor CCR6 on human effector memory CD8+ T cells. Eur J Immunol 37:54–65. doi:10.1002/eji.200636251

    Article  CAS  PubMed  Google Scholar 

  51. Kucharzik T, Hudson JT 3rd, Waikel RL, Martin WD, Williams IR (2002) CCR6 expression distinguishes mouse myeloid and lymphoid dendritic cell subsets: demonstration using a CCR6 EGFP knock-in mouse. Eur J Immunol 32:104–112. doi:10.1002/1521-4141(200201)32:1<104::AID-IMMU104>3.0.CO;2-C

    Article  CAS  PubMed  Google Scholar 

  52. Liao F, Rabin RL, Smith CS, Sharma G, Nutman TB, Farber JM (1999) CC-chemokine receptor 6 is expressed on diverse memory subsets of T cells and determines responsiveness to macrophage inflammatory protein 3 alpha. J Immunol 162:186–194

    CAS  PubMed  Google Scholar 

  53. Tanaka Y, Imai T, Baba M, Ishikawa I, Uehira M, Nomiyama H, Yoshie O (1999) Selective expression of liver and activation-regulated chemokine (LARC) in intestinal epithelium in mice and humans. Eur J Immunol 29:633–642. doi:10.1002/(SICI)1521-4141(199902)29:02<633::AID-IMMU633>3.0.CO;2-I

    Article  CAS  PubMed  Google Scholar 

  54. Sierro F, Dubois B, Coste A, Kaiserlian D, Kraehenbuhl JP, Sirard JC (2001) Flagellin stimulation of intestinal epithelial cells triggers CCL20-mediated migration of dendritic cells. Proc Natl Acad Sci U S A 98:13722–13727. doi:10.1073/pnas.241308598

    Article  CAS  PubMed  Google Scholar 

  55. Cook DN, Prosser DM, Forster R, Zhang J, Kuklin NA, Abbondanzo SJ, Niu XD, Chen SC, Manfra DJ, Wiekowski MT, Sullivan LM, Smith SR, Greenberg HB, Narula SK, Lipp M, Lira SA (2000) CCR6 mediates dendritic cell localization, lymphocyte homeostasis, and immune responses in mucosal tissue. Immunity 12:495–503. doi:10.1016/S1074-7613(00)80201-0

    Article  CAS  PubMed  Google Scholar 

  56. Lugering A, Floer M, Westphal S, Maaser C, Spahn TW, Schmidt MA, Domschke W, Williams IR, Kucharzik T (2005) Absence of CCR6 inhibits CD4+ regulatory T-cell development and M-cell formation inside Peyer's patches. Am J Pathol 166:1647–1654

    PubMed  Google Scholar 

  57. Cheng H, Leblond CP (1974) Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. V. Unitarian Theory of the origin of the four epithelial cell types. Am J Anat 141:537–561. doi:10.1002/aja.1001410407

    Article  CAS  PubMed  Google Scholar 

  58. Kerneis S, Bogdanova A, Kraehenbuhl JP, Pringault E (1997) Conversion by Peyer's patch lymphocytes of human enterocytes into M cells that transport bacteria. Science 277:949–952. doi:10.1126/science.277.5328.949

    Article  CAS  PubMed  Google Scholar 

  59. El Bahi S, Caliot E, Bens M, Bogdanova A, Kerneis S, Kahn A, Vandewalle A, Pringault E (2002) Lymphoepithelial interactions trigger specific regulation of gene expression in the M cell-containing follicle-associated epithelium of Peyer's patches. J Immunol 168:3713–3720

    CAS  PubMed  Google Scholar 

  60. Tyrer P, Ruth Foxwell A, Kyd J, Harvey M, Sizer P, Cripps A (2002) Validation and quantitation of an in vitro M-cell model. Biochem Biophys Res Commun 299:377–383. doi:10.1016/S0006-291X(02)02631-1

    Article  CAS  PubMed  Google Scholar 

  61. Blanco LP, DiRita VJ (2006) Bacterial-associated cholera toxin and GM1 binding are required for transcytosis of classical biotype Vibrio cholerae through an in vitro M cell model system. Cell Microbiol 8:982–998. doi:10.1111/j.1462-5822.2005.00681.x

    Article  CAS  PubMed  Google Scholar 

  62. Golovkina TV, Shlomchik M, Hannum L, Chervonsky A (1999) Organogenic role of B lymphocytes in mucosal immunity. Science 286:1965–1968. doi:10.1126/science.286.5446.1965

    Article  CAS  PubMed  Google Scholar 

  63. Debard N, Sierro F, Browning J, Kraehenbuhl JP (2001) Effect of mature lymphocytes and lymphotoxin on the development of the follicle-associated epithelium and M cells in mouse Peyer's patches. Gastroenterology 120:1173–1182. doi:10.1053/gast.2001.22476

    Article  CAS  PubMed  Google Scholar 

  64. Adachi S, Yoshida H, Kataoka H, Nishikawa S (1997) Three distinctive steps in Peyer's patch formation of murine embryo. Int Immunol 9:507–514. doi:10.1093/intimm/9.4.507

    Article  CAS  PubMed  Google Scholar 

  65. Sharma R, Schumacher U, Adam E (1998) Lectin histochemistry reveals the appearance of M-cells in Peyer's patches of SCID mice after syngeneic normal bone marrow transplantation. J Histochem Cytochem 46:143–148

    CAS  PubMed  Google Scholar 

  66. Lelouard H, Sahuquet A, Reggio H, Montcourrier P (2001) Rabbit M cells and dome enterocytes are distinct cell lineages. J Cell Sci 114:2077–2083

    CAS  PubMed  Google Scholar 

  67. Jang MH, Kweon MN, Iwatani K, Yamamoto M, Terahara K, Sasakawa C, Suzuki T, Nochi T, Yokota Y, Rennert PD, Hiroi T, Tamagawa H, Iijima H, Kunisawa J, Yuki Y, Kiyono H (2004) Intestinal villous M cells: an antigen entry site in the mucosal epithelium. Proc Natl Acad Sci U S A 101:6110–6115. doi:10.1073/pnas.0400969101

    Article  CAS  PubMed  Google Scholar 

  68. Niess JH, Brand S, Gu X, Landsman L, Jung S, McCormick BA, Vyas JM, Boes M, Ploegh HL, Fox JG, Littman DR, Reinecker HC (2005) CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science 307:254–258. doi:10.1126/science.1102901

    Article  CAS  PubMed  Google Scholar 

  69. Rescigno M, Urbano M, Valzasina B, Francolini M, Rotta G, Bonasio R, Granucci F, Kraehenbuhl JP, Ricciardi-Castagnoli P (2001) Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol 2:361–367. doi:10.1038/86373

    Article  CAS  PubMed  Google Scholar 

  70. Taylor RT, Lugering A, Newell KA, Williams IR (2004) Intestinal cryptopatch formation in mice requires lymphotoxin alpha and the lymphotoxin beta receptor. J Immunol 173:7183–7189

    CAS  PubMed  Google Scholar 

  71. Allen CD, Cyster JG (2008) Follicular dendritic cell networks of primary follicles and germinal centers: phenotype and function. Semin Immunol 20:14–25. doi:10.1016/j.smim.2007.12.001

    Article  CAS  PubMed  Google Scholar 

  72. Katakai T, Hara T, Lee JH, Gonda H, Sugai M, Shimizu A (2004) A novel reticular stromal structure in lymph node cortex: an immuno-platform for interactions among dendritic cells, T cells and B cells. Int Immunol 16:1133–1142. doi:10.1093/intimm/dxh113

    Article  CAS  PubMed  Google Scholar 

  73. Katakai T, Hara T, Sugai M, Gonda H, Shimizu A (2004) Lymph node fibroblastic reticular cells construct the stromal reticulum via contact with lymphocytes. J Exp Med 200:783–795. doi:10.1084/jem.20040254

    Article  CAS  PubMed  Google Scholar 

  74. Link A, Vogt TK, Favre S, Britschgi MR, Acha-Orbea H, Hinz B, Cyster JG, Luther SA (2007) Fibroblastic reticular cells in lymph nodes regulate the homeostasis of naive T cells. Nat Immunol 8:1255–1265. doi:10.1038/ni1513

    Article  CAS  PubMed  Google Scholar 

  75. Gretz JE, Anderson AO, Shaw S (1997) Cords, channels, corridors and conduits: critical architectural elements facilitating cell interactions in the lymph node cortex. Immunol Rev 156:11–24. doi:10.1111/j.1600-065X.1997.tb00955.x

    Article  CAS  PubMed  Google Scholar 

  76. Gretz JE, Kaldjian EP, Anderson AO, Shaw S (1996) Sophisticated strategies for information encounter in the lymph node: the reticular network as a conduit of soluble information and a highway for cell traffic. J Immunol 157:495–499

    CAS  PubMed  Google Scholar 

  77. Sixt M, Kanazawa N, Selg M, Samson T, Roos G, Reinhardt DP, Pabst R, Lutz MB, Sorokin L (2005) The conduit system transports soluble antigens from the afferent lymph to resident dendritic cells in the T cell area of the lymph node. Immunity 22:19–29. doi:10.1016/j.immuni.2004.11.013

    Article  CAS  PubMed  Google Scholar 

  78. Bajenoff M, Egen JG, Koo LY, Laugier JP, Brau F, Glaichenhaus N, Germain RN (2006) Stromal cell networks regulate lymphocyte entry, migration, and territoriality in lymph nodes. Immunity 25:989–1001. doi:10.1016/j.immuni.2006.10.011

    Article  CAS  PubMed  Google Scholar 

  79. Cyster JG (1999) Chemokines and cell migration in secondary lymphoid organs. Science 286:2098–2102. doi:10.1126/science.286.5447.2098

    Article  CAS  PubMed  Google Scholar 

  80. Carlsen HS, Haraldsen G, Brandtzaeg P, Baekkevold ES (2005) Disparate lymphoid chemokine expression in mice and men: no evidence of CCL21 synthesis by human high endothelial venules. Blood 106:444–446. doi:10.1182/blood-2004-11-4353

    Article  CAS  PubMed  Google Scholar 

  81. Baekkevold ES, Yamanaka T, Palframan RT, Carlsen HS, Reinholt FP, von Andrian UH, Brandtzaeg P, Haraldsen G (2001) The CCR7 ligand elc (CCL19) is transcytosed in high endothelial venules and mediates T cell recruitment. J Exp Med 193:1105–1112. doi:10.1084/jem.193.9.1105

    Article  CAS  PubMed  Google Scholar 

  82. Lee JW, Epardaud M, Sun J, Becker JE, Cheng AC, Yonekura AR, Heath JK, Turley SJ (2007) Peripheral antigen display by lymph node stroma promotes T cell tolerance to intestinal self. Nat Immunol 8:181–190. doi:10.1038/ni1427

    Article  CAS  PubMed  Google Scholar 

  83. Svensson M, Maroof A, Ato M, Kaye PM (2004) Stromal cells direct local differentiation of regulatory dendritic cells. Immunity 21:805–816. doi:10.1016/j.immuni.2004.10.012

    Article  CAS  PubMed  Google Scholar 

  84. Hammerschmidt SI, Ahrendt M, Bode U, Wahl B, Kremmer E, Forster R, Pabst O (2008) Stromal mesenteric lymph node cells are essential for the generation of gut-homing T cells in vivo. J Exp Med 205:2483–2490. doi:10.1084/jem.20080039

    Article  CAS  PubMed  Google Scholar 

  85. Okuda M, Togawa A, Wada H, Nishikawa S (2007) Distinct activities of stromal cells involved in the organogenesis of lymph nodes and Peyer's patches. J Immunol 179:804–811

    CAS  PubMed  Google Scholar 

  86. Katakai T, Suto H, Sugai M, Gonda H, Togawa A, Suematsu S, Ebisuno Y, Katagiri K, Kinashi T, Shimizu A (2008) Organizer-like reticular stromal cell layer common to adult secondary lymphoid organs. J Immunol 181:6189–6200

    CAS  PubMed  Google Scholar 

  87. Miyawaki S, Nakamura Y, Suzuka H, Koba M, Yasumizu R, Ikehara S, Shibata Y (1994) A new mutation, aly, that induces a generalized lack of lymph nodes accompanied by immunodeficiency in mice. Eur J Immunol 24:429–434. doi:10.1002/eji.1830240224

    Article  CAS  PubMed  Google Scholar 

  88. Matsumoto M, Iwamasa K, Rennert PD, Yamada T, Suzuki R, Matsushima A, Okabe M, Fujita S, Yokoyama M (1999) Involvement of distinct cellular compartments in the abnormal lymphoid organogenesis in lymphotoxin-alpha-deficient mice and alymphoplasia (aly) mice defined by the chimeric analysis. J Immunol 163:1584–1591

    CAS  PubMed  Google Scholar 

  89. Shinkura R, Kitada K, Matsuda F, Tashiro K, Ikuta K, Suzuki M, Kogishi K, Serikawa T, Honjo T (1999) Alymphoplasia is caused by a point mutation in the mouse gene encoding Nf-kappa b-inducing kinase. Nat Genet 22:74–77. doi:10.1038/8780

    Article  CAS  PubMed  Google Scholar 

  90. De Togni P, Goellner J, Ruddle NH, Streeter PR, Fick A, Mariathasan S, Smith SC, Carlson R, Shornick LP, Strauss-Schoenberger J (1994) Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin. Science 264:703–707. doi:10.1126/science.8171322

    Article  PubMed  Google Scholar 

  91. Yin L, Wu L, Wesche H, Arthur CD, White JM, Goeddel DV, Schreiber RD (2001) Defective lymphotoxin-beta receptor-induced NF-kappaB transcriptional activity in NIK-deficient mice. Science 291:2162–2165. doi:10.1126/science.1058453

    Article  CAS  PubMed  Google Scholar 

  92. Futterer A, Mink K, Luz A, Kosco-Vilbois MH, Pfeffer K (1998) The lymphotoxin beta receptor controls organogenesis and affinity maturation in peripheral lymphoid tissues. Immunity 9:59–70. doi:10.1016/S1074-7613(00)80588-9

    Article  CAS  PubMed  Google Scholar 

  93. Rennert PD, Browning JL, Mebius R, Mackay F, Hochman PS (1996) Surface lymphotoxin alpha/beta complex is required for the development of peripheral lymphoid organs. J Exp Med 184:1999–2006. doi:10.1084/jem.184.5.1999

    Article  CAS  PubMed  Google Scholar 

  94. Adachi S, Yoshida H, Honda K, Maki K, Saijo K, Ikuta K, Saito T, Nishikawa S (1998) Essential role of IL-7 receptor alpha in the formation of Peyer's patch anlage. Int Immunol 10:1–6. doi:10.1093/intimm/10.1.1

    Article  CAS  PubMed  Google Scholar 

  95. Yoshida H, Honda K, Shinkura R, Adachi S, Nishikawa S, Maki K, Ikuta K, Nishikawa SI (1999) IL-7 receptor alpha+ CD3(−) cells in the embryonic intestine induces the organizing center of Peyer's patches. Int Immunol 11:643–655. doi:10.1093/intimm/11.5.643

    Article  CAS  PubMed  Google Scholar 

  96. Hashi H, Yoshida H, Honda K, Fraser S, Kubo H, Awane M, Takabayashi A, Nakano H, Yamaoka Y, Nishikawa S (2001) Compartmentalization of Peyer's patch anlagen before lymphocyte entry. J Immunol 166:3702–3709

    CAS  PubMed  Google Scholar 

  97. Honda K, Nakano H, Yoshida H, Nishikawa S, Rennert P, Ikuta K, Tamechika M, Yamaguchi K, Fukumoto T, Chiba T, Nishikawa SI (2001) Molecular basis for hematopoietic/mesenchymal interaction during initiation of Peyer's patch organogenesis. J Exp Med 193:621–630. doi:10.1084/jem.193.5.621

    Article  CAS  PubMed  Google Scholar 

  98. Eberl G, Marmon S, Sunshine MJ, Rennert PD, Choi Y, Littman DR (2004) An essential function for the nuclear receptor RORgamma(t) in the generation of fetal lymphoid tissue inducer cells. Nat Immunol 5:64–73. doi:10.1038/ni1022

    Article  CAS  PubMed  Google Scholar 

  99. Rossi SW, Kim MY, Leibbrandt A, Parnell SM, Jenkinson WE, Glanville SH, McConnell FM, Scott HS, Penninger JM, Jenkinson EJ, Lane PJ, Anderson G (2007) RANK signals from CD4(+) 3(−) inducer cells regulate development of Aire-expressing epithelial cells in the thymic medulla. J Exp Med 204:1267–1272. doi:10.1084/jem.20062497

    Article  CAS  PubMed  Google Scholar 

  100. Kim MY, Rossi S, Withers D, McConnell F, Toellner KM, Gaspal F, Jenkinson E, Anderson G, Lane PJ (2008) Heterogeneity of lymphoid tissue inducer cell populations present in embryonic and adult mouse lymphoid tissues. Immunology 124:166–174

    Article  CAS  PubMed  Google Scholar 

  101. Mebius RE, Rennert P, Weissman IL (1997) Developing lymph nodes collect CD4+CD3− LTbeta+ cells that can differentiate to APC, NK cells, and follicular cells but not T or B cells. Immunity 7:493–504. doi:10.1016/S1074-7613(00)80371-4

    Article  CAS  PubMed  Google Scholar 

  102. Finke D, Acha-Orbea H, Mattis A, Lipp M, Kraehenbuhl J (2002) CD4+CD3− cells induce Peyer's patch development: role of alpha4beta1 integrin activation by CXCR5. Immunity 17:363–373. doi:10.1016/S1074-7613(02)00395-3

    Article  CAS  PubMed  Google Scholar 

  103. Dejardin E, Droin NM, Delhase M, Haas E, Cao Y, Makris C, Li ZW, Karin M, Ware CF, Green DR (2002) The lymphotoxin-beta receptor induces different patterns of gene expression via two NF-kappaB pathways. Immunity 17:525–535. doi:10.1016/S1074-7613(02)00423-5

    Article  CAS  PubMed  Google Scholar 

  104. Hehlgans T, Pfeffer K (2005) The intriguing biology of the tumour necrosis factor/tumour necrosis factor receptor superfamily: players, rules and the games. Immunology 115:1–20. doi:10.1111/j.1365-2567.2005.02143.x

    Article  CAS  PubMed  Google Scholar 

  105. Weih F, Caamano J (2003) Regulation of secondary lymphoid organ development by the nuclear factor-kappaB signal transduction pathway. Immunol Rev 195:91–105. doi:10.1034/j.1600-065X.2003.00064.x

    Article  CAS  PubMed  Google Scholar 

  106. Browning JL, Allaire N, Ngam-Ek A, Notidis E, Hunt J, Perrin S, Fava RA (2005) Lymphotoxin-beta receptor signaling is required for the homeostatic control of HEV differentiation and function. Immunity 23:539–550. doi:10.1016/j.immuni.2005.10.002

    Article  CAS  PubMed  Google Scholar 

  107. Furtado GC, Marinkovic T, Martin AP, Garin A, Hoch B, Hubner W, Chen BK, Genden E, Skobe M, Lira SA (2007) Lymphotoxin beta receptor signaling is required for inflammatory lymphangiogenesis in the thyroid. Proc Natl Acad Sci U S A 104:5026–5031. doi:10.1073/pnas.0606697104

    Article  CAS  PubMed  Google Scholar 

  108. Liao S, Ruddle NH (2006) Synchrony of high endothelial venules and lymphatic vessels revealed by immunization. J Immunol 177:3369–3379

    CAS  PubMed  Google Scholar 

  109. Rumbo M, Sierro F, Debard N, Kraehenbuhl JP, Finke D (2004) Lymphotoxin beta receptor signaling induces the chemokine CCL20 in intestinal epithelium. Gastroenterology 127:213–223. doi:10.1053/j.gastro.2004.04.018

    Article  CAS  PubMed  Google Scholar 

  110. Rennert PD, James D, Mackay F, Browning JL, Hochman PS (1998) Lymph node genesis is induced by signaling through the lymphotoxin beta receptor. Immunity 9:71–79. doi:10.1016/S1074-7613(00)80589-0

    Article  CAS  PubMed  Google Scholar 

  111. Kuprash DV, Tumanov AV, Liepinsh DJ, Koroleva EP, Drutskaya MS, Kruglov AA, Shakhov AN, Southon E, Murphy WJ, Tessarollo L, Grivennikov SI, Nedospasov SA (2005) Novel tumor necrosis factor-knockout mice that lack Peyer's patches. Eur J Immunol 35:1592–1600. doi:10.1002/eji.200526119

    Article  CAS  PubMed  Google Scholar 

  112. Pfeffer K, Matsuyama T, Kundig TM, Wakeham A, Kishihara K, Shahinian A, Wiegmann K, Ohashi PS, Kronke M, Mak TW (1993) Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection. Cell 73:457–467. doi:10.1016/0092-8674(93)90134-C

    Article  CAS  PubMed  Google Scholar 

  113. Koni PA, Flavell RA (1998) A role for tumor necrosis factor receptor type 1 in gut-associated lymphoid tissue development: genetic evidence of synergism with lymphotoxin beta. J Exp Med 187:1977–1983. doi:10.1084/jem.187.12.1977

    Article  CAS  PubMed  Google Scholar 

  114. Yoshida H, Naito A, Inoue J, Satoh M, Santee-Cooper SM, Ware CF, Togawa A, Nishikawa S (2002) Different cytokines induce surface lymphotoxin-alphabeta on IL-7 receptor-alpha cells that differentially engender lymph nodes and Peyer's patches. Immunity 17:823–833. doi:10.1016/S1074-7613(02)00479-X

    Article  CAS  PubMed  Google Scholar 

  115. Mold JE, Michaelsson J, Burt TD, Muench MO, Beckerman KP, Busch MP, Lee TH, Nixon DF, McCune JM (2008) Maternal alloantigens promote the development of tolerogenic fetal regulatory T cells in utero. Science 322:1562–1565. doi:10.1126/science.1164511

    Article  CAS  PubMed  Google Scholar 

  116. Finke D, Meier D (2006) Molecular networks orchestrating GALT development. CTMI 308:19–57

    CAS  Google Scholar 

  117. Sitnicka E, Brakebusch C, Martensson IL, Svensson M, Agace WW, Sigvardsson M, Buza-Vidas N, Bryder D, Cilio CM, Ahlenius H, Maraskovsky E, Peschon JJ, Jacobsen SE (2003) Complementary signaling through flt3 and interleukin-7 receptor alpha is indispensable for fetal and adult B cell genesis. J Exp Med 198:1495–1506. doi:10.1084/jem.20031152

    Article  CAS  PubMed  Google Scholar 

  118. Cao X, Shores EW, Hu-Li J, Anver MR, Kelsall BL, Russell SM, Drago J, Noguchi M, Grinberg A, Bloom ET et al (1995) Defective lymphoid development in mice lacking expression of the common cytokine receptor gamma chain. Immunity 2:223–238. doi:10.1016/1074-7613(95)90047-0

    Article  CAS  PubMed  Google Scholar 

  119. Kang J, Der S (2004) Cytokine functions in the formative stages of a lymphocyte's life. Curr Opin Immunol 16:180–190. doi:10.1016/j.coi.2004.02.002

    Article  CAS  PubMed  Google Scholar 

  120. Luther SA, Ansel KM, Cyster JG (2003) Overlapping roles of CXCL13, interleukin 7 receptor α, and CCR7 ligands in lymph node development. J Exp Med 197:1191–1198. doi:10.1084/jem.20021294

    Article  CAS  PubMed  Google Scholar 

  121. Park SY, Saijo K, Takahashi T, Osawa M, Arase H, Hirayama N, Miyake K, Nakauchi H, Shirasawa T, Saito T (1995) Developmental defects of lymphoid cells in Jak3 kinase-deficient mice. Immunity 3:771–782. doi:10.1016/1074-7613(95)90066-7

    Article  CAS  PubMed  Google Scholar 

  122. Pandey A, Ozaki K, Baumann H, Levin SD, Puel A, Farr AG, Ziegler SF, Leonard WJ, Lodish HF (2000) Cloning of a receptor subunit required for signaling by thymic stromal lymphopoietin. Nat Immunol 1:59–64. doi:10.1038/76923

    Article  CAS  PubMed  Google Scholar 

  123. Park LS, Martin U, Garka K, Gliniak B, Di Santo JP, Muller W, Largaespada DA, Copeland NG, Jenkins NA, Farr AG, Ziegler SF, Morrissey PJ, Paxton R, Sims JE (2000) Cloning of the murine thymic stromal lymphopoietin (TSLP) receptor: formation of a functional heteromeric complex requires interleukin 7 receptor. J Exp Med 192:659–670. doi:10.1084/jem.192.5.659

    Article  CAS  PubMed  Google Scholar 

  124. Al-Shami A, Spolski R, Kelly J, Fry T, Schwartzberg PL, Pandey A, Mackall CL, Leonard WJ (2004) A role for thymic stromal lymphopoietin in CD4(+) T cell development. J Exp Med 200:159–168. doi:10.1084/jem.20031975

    Article  CAS  PubMed  Google Scholar 

  125. Forster R, Schubel A, Breitfeld D, Kremmer E, Renner-Muller I, Wolf E, Lipp M (1999) CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs. Cell 99:23–33. doi:10.1016/S0092-8674(00)80059-8

    Article  CAS  PubMed  Google Scholar 

  126. Nakano H, Mori S, Yonekawa H, Nariuchi H, Matsuzawa A, Kakiuchi T (1998) A novel mutant gene involved in T-lymphocyte-specific homing into peripheral lymphoid organs on mouse chromosome 4. Blood 91:2886–2895

    CAS  PubMed  Google Scholar 

  127. Ohl L, Henning G, Krautwald S, Lipp M, Hardtke S, Bernhardt G, Pabst O, Förster R (2003) Cooperative mechanisms of CXCR5 and CCR7 in development and organization of secondary lymphoid organs. J Exp Med 197:1199–1204. doi:10.1084/jem.20030169

    Article  CAS  PubMed  Google Scholar 

  128. Metcalf D (1993) Hematopoietic regulators: redundancy or subtlety? Blood 82:3515–3523

    CAS  PubMed  Google Scholar 

  129. Meier D, Bornmann C, Chappaz S, Schmutz S, Otten LA, Ceredig R, Acha-Orbea H, Finke D (2007) Ectopic lymphoid-organ development occurs through interleukin 7-mediated enhanced survival of lymphoid-tissue-inducer cells. Immunity 26:643–654. doi:10.1016/j.immuni.2007.04.009

    Article  CAS  PubMed  Google Scholar 

  130. Kondo S (2002) The reaction-diffusion system: a mechanism for autonomous pattern formation in the animal skin. Genes Cells 7:535–541. doi:10.1046/j.1365-2443.2002.00543.x

    Article  CAS  PubMed  Google Scholar 

  131. Croker BA, Kiu H, Nicholson SE (2008) SOCS regulation of the JAK/STAT signalling pathway. Semin Cell Dev Biol 19:414–422. doi:10.1016/j.semcdb.2008.07.010

    Article  CAS  PubMed  Google Scholar 

  132. Fernandez-Botran R, Chilton PM, Ma Y (1996) Soluble cytokine receptors: their roles in immunoregulation, disease, and therapy. Adv Immunol 63:269–336. doi:10.1016/S0065-2776(08)60858-5

    Article  CAS  PubMed  Google Scholar 

  133. Veiga-Fernandes H, Coles MC, Foster KE, Patel A, Williams A, Natarajan D, Barlow A, Pachnis V, Kioussis D (2007) Tyrosine kinase receptor RET is a key regulator of Peyer's patch organogenesis. Nature 446:547–551. doi:10.1038/nature05597

    Article  CAS  PubMed  Google Scholar 

  134. Sun Z, Unutmaz D, Zou YR, Sunshine MJ, Pierani A, Brenner-Morton S, Mebius RE, Littman DR (2000) Requirement for RORgamma in thymocyte survival and lymphoid organ development. Science 288:2369–2373. doi:10.1126/science.288.5475.2369

    Article  CAS  PubMed  Google Scholar 

  135. Yokota Y, Mansouri A, Mori S, Sugawara S, Adachi S, Nishikawa S, Gruss P (1999) Development of peripheral lymphoid organs and natural killer cells depends on the helix-loop-helix inhibitor Id2. Nature 397:702–706. doi:10.1038/17812

    Article  CAS  PubMed  Google Scholar 

  136. Kurebayashi S, Ueda E, Sakaue M, Patel DD, Medvedev A, Zhang F, Jetten AM (2000) Retinoid-related orphan receptor gamma (RORgamma) is essential for lymphoid organogenesis and controls apoptosis during thymopoiesis. Proc Natl Acad Sci U S A 97:10132–10137. doi:10.1073/pnas.97.18.10132

    Article  CAS  PubMed  Google Scholar 

  137. Boos MD, Yokota Y, Eberl G, Kee BL (2007) Mature natural killer cell and lymphoid tissue-inducing cell development requires Id2-mediated suppression of E protein activity. J Exp Med 204:1119–1130. doi:10.1084/jem.20061959

    Article  CAS  PubMed  Google Scholar 

  138. Yoshida H, Kawamoto H, Santee S, Hashi H, Honda K, Nishikawa S, Ware C, Katsura Y, Nishikawa S (2001) Expression of alpha(4) beta(7) integrin defines a distinct pathway of lymphoid progenitors committed to T cells, fetal intestinal lymphotoxin producer, NK, and dendritic cells. J Immunol 167:2511–2521

    CAS  PubMed  Google Scholar 

  139. Mebius RE, Miyamoto T, Christensen J, Domen J, Cupedo T, Weissman IL, Akashi K (2001) The fetal liver counterpart of adult common lymphoid progenitors gives rise to all lymphoid lineages, CD45+CD4+CD3− cells, as well as macrophages. J Immunol 166:6593–6601

    CAS  PubMed  Google Scholar 

  140. Murray AM, Simm B, Beagley KW (1998) Cytokine gene expression in murine fetal intestine: potential for extrathymic T cell development. Cytokine 10:337–345. doi:10.1006/cyto.1997.0302

    Article  CAS  PubMed  Google Scholar 

  141. Cupedo T, Crellin NK, Papazian N, Rombouts EJ, Weijer K, Grogan JL, Fibbe WE, Cornelissen JJ, Spits H (2009) Human fetal lymphoid tissue-inducer cells are interleukin 17-producing precursors to RORC+ CD127+ natural killer-like cells. Nat Immunol 10:66–74. doi:10.1038/ni.1668

    Article  CAS  PubMed  Google Scholar 

  142. Luci C, Reynders A, Ivanov II, Cognet C, Chiche L, Chasson L, Hardwigsen J, Anguiano E, Banchereau J, Chaussabel D, Dalod M, Littman DR, Vivier E, Tomasello E (2009) Influence of the transcription factor RORgammat on the development of NKp46+ cell populations in gut and skin. Nat Immunol 10:75–82. doi:10.1038/ni.1681

    Article  CAS  PubMed  Google Scholar 

  143. Cella M, Fuchs A, Vermi W, Facchetti F, Otero K, Lennerz JK, Doherty JM, Mills JC, Colonna M (2009) A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity. Nature 457:722–725. doi:10.1038/nature07537

    Article  CAS  PubMed  Google Scholar 

  144. Sanos SL, Bui VL, Mortha A, Oberle K, Heners C, Johner C, Diefenbach A (2009) RORgammat and commensal microflora are required for the differentiation of mucosal interleukin 22-producing NKp46+ cells. Nat Immunol 10:83–91. doi:10.1038/ni.1684

    Article  CAS  PubMed  Google Scholar 

  145. Satoh-Takayama N, Vosshenrich CA, Lesjean-Pottier S, Sawa S, Lochner M, Rattis F, Mention JJ, Thiam K, Cerf-Bensussan N, Mandelboim O, Eberl G, Di Santo JP (2008) Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense. Immunity 29:958–970. doi:10.1016/j.immuni.2008.11.001

    Article  CAS  PubMed  Google Scholar 

  146. Takatori H, Kanno Y, Watford WT, Tato CM, Weiss G, Ivanov II, Littman DR, O'Shea JJ (2008) Lymphoid tissue inducer-like cells are an innate source of IL-17 and IL-22. J Exp Med 206:35–41

    Article  PubMed  CAS  Google Scholar 

  147. Chinen H, Matsuoka K, Sato T, Kamada N, Okamoto S, Hisamatsu T, Kobayashi T, Hasegawa H, Sugita A, Kinjo F, Fujita J, Hibi T (2007) Lamina propria c-kit+ immune precursors reside in human adult intestine and differentiate into natural killer cells. Gastroenterology 133:559–573. doi:10.1053/j.gastro.2007.05.017

    Article  CAS  PubMed  Google Scholar 

  148. Yokota Y, Mori S, Nishikawa SI, Mansouri A, Gruss P, Kusunoki T, Katakai T, Shimizu A (2000) The helix-loop-helix inhibitor Id2 and cell differentiation control. Curr Top Microbiol Immunol 251:35–41

    CAS  PubMed  Google Scholar 

  149. Eberl G, Littman DR (2004) Thymic origin of intestinal αβ T cells revealed by fate mapping of RORγt+ cells. Science 305:248–251. doi:10.1126/science.1096472

    Article  CAS  PubMed  Google Scholar 

  150. Kim MY, Gaspal FM, Wiggett HE, McConnell FM, Gulbranson-Judge A, Raykundalia C, Walker LS, Goodall MD, Lane PJ (2003) CD4(+) CD3(−) accessory cells costimulate primed CD4 T cells through OX40 and CD30 at sites where T cells collaborate with B cells. Immunity 18:643–654. doi:10.1016/S1074-7613(03)00110-9

    Article  CAS  PubMed  Google Scholar 

  151. Kim MY, Toellner KM, White A, McConnell FM, Gaspal FM, Parnell SM, Jenkinson E, Anderson G, Lane PJ (2006) Neonatal and adult CD4+ CD3− cells share similar gene expression profile, and neonatal cells up-regulate OX40 ligand in response to TL1A (TNFSF15). J Immunol 177:3074–3081

    CAS  PubMed  Google Scholar 

  152. Kim MY, Anderson G, White A, Jenkinson E, Arlt W, Martensson IL, Erlandsson L, Lane PJ (2005) OX40 ligand and CD30 ligand are expressed on adult but not neonatal CD4+CD3− inducer cells: evidence that IL-7 signals regulate CD30 ligand but not OX40 ligand expression. J Immunol 174:6686–6691

    CAS  PubMed  Google Scholar 

  153. Lane PJ, Gaspal FM, Kim MY (2005) Two sides of a cellular coin: CD4(+) CD3− cells regulate memory responses and lymph-node organization. Nat Rev Immunol 5:655–660. doi:10.1038/nri1665

    Article  CAS  PubMed  Google Scholar 

  154. Sawa Y, Arima Y, Ogura H, Kitabayashi C, Jiang JJ, Fukushima T, Kamimura D, Hirano T, Murakami M (2009) Hepatic interleukin-7 expression regulates T cell responses. Immunity 30:447–457. doi:10.1016/j.immuni.2009.01.007

    Article  CAS  PubMed  Google Scholar 

  155. Scandella E, Bolinger B, Lattmann E, Miller S, Favre S, Littman DR, Finke D, Luther SA, Junt T, Ludewig B (2008) Restoration of lymphoid organ integrity through the interaction of lymphoid tissue-inducer cells with stroma of the T cell zone. Nat Immunol 9:667–675. doi:10.1038/ni.1605

    Article  CAS  PubMed  Google Scholar 

  156. Ettinger R, Browning JL, Michie SA, van Ewijk W, McDevitt HO (1996) Disrupted splenic architecture, but normal lymph node development in mice expressing a soluble lymphotoxin-beta receptor-IgG1 fusion protein. Proc Natl Acad Sci U S A 93:13102–13107. doi:10.1073/pnas.93.23.13102

    Article  CAS  PubMed  Google Scholar 

  157. Rennert PD, Browning JL, Hochman PS (1997) Selective disruption of lymphotoxin ligands reveals a novel set of mucosal lymph nodes and unique effects on lymph node cellular organization. Int Immunol 9:1627–1639. doi:10.1093/intimm/9.11.1627

    Article  CAS  PubMed  Google Scholar 

  158. Gonzalez M, Mackay F, Browning JL, Kosco-Vilbois MH, Noelle RJ (1998) The sequential role of lymphotoxin and B cells in the development of splenic follicles. J Exp Med 187:997–1007. doi:10.1084/jem.187.7.997

    Article  CAS  PubMed  Google Scholar 

  159. Tumanov AV, Kuprash DV, Mach JA, Nedospasov SA, Chervonsky AV (2004) Lymphotoxin and TNF produced by B cells are dispensable for maintenance of the follicle-associated epithelium but are required for development of lymphoid follicles in the Peyer's patches. J Immunol 173:86–91

    CAS  PubMed  Google Scholar 

  160. Ware CF, VanArsdale TL, Crowe PD, Browning JL (1995) The ligands and receptors of the lymphotoxin system. Curr Top Microbiol Immunol 198:175–218

    CAS  PubMed  Google Scholar 

  161. Mackay F, Browning JL (1998) Turning off follicular dendritic cells. Nature 395:26–27. doi:10.1038/25630

    Article  CAS  PubMed  Google Scholar 

  162. Smith MW, James PS, Tivey DR (1987) M cell numbers increase after transfer of SPF mice to a normal animal house environment. Am J Pathol 128:385–389

    CAS  PubMed  Google Scholar 

  163. Karapetian O, Shakhov AN, Kraehenbuhl JP, Acha-Orbea H (1994) Retroviral infection of neonatal Peyer's patch lymphocytes: the mouse mammary tumor virus model. J Exp Med 180:1511–1516. doi:10.1084/jem.180.4.1511

    Article  CAS  PubMed  Google Scholar 

  164. Bevilacqua G, Marchetti A, Biondi R (1989) Ultrastructural features of the intestinal absorption of mouse mammary tumor virus in newborn BALB/cfRIII mice. Gastroenterology 96:139–145

    CAS  PubMed  Google Scholar 

  165. Hainaut P, Francois C, Calberg-Bacq CM, Vaira D, Osterrieth PM (1983) Peroral infection of suckling mice with milk-borne mouse mammary tumour virus: uptake of the main viral antigens by the gut. J Gen Virol 64(Pt 12):2535–2548. doi:10.1099/0022-1317-64-12-2535

    Article  PubMed  Google Scholar 

  166. Acha-Orbea H, Finke D, Attinger A, Schmid S, Wehrli N, Vacheron S, Xenarios I, Scarpellino L, Toellner KM, MacLennan IC, Luther SA (1999) Interplays between mouse mammary tumor virus and the cellular and humoral immune response. Immunol Rev 168:287–303. doi:10.1111/j.1600-065X.1999.tb01299.x

    Article  CAS  PubMed  Google Scholar 

  167. Girardin SE, Boneca IG, Carneiro LA, Antignac A, Jehanno M, Viala J, Tedin K, Taha MK, Labigne A, Zahringer U, Coyle AJ, DiStefano PS, Bertin J, Sansonetti PJ, Philpott DJ (2003) Nod1 detects a unique muropeptide from gram-negative bacterial peptidoglycan. Science 300:1584–1587. doi:10.1126/science.1084677

    Article  CAS  PubMed  Google Scholar 

  168. Fagarasan S, Muramatsu M, Suzuki K, Nagaoka H, Hiai H, Honjo T (2002) Critical roles of activation-induced cytidine deaminase in the homeostasis of gut flora. Science 298:1424–1427. doi:10.1126/science.1077336

    Article  CAS  PubMed  Google Scholar 

  169. Hamann A, Andrew DP, Jablonski-Westrich D, Holzmann B, Butcher EC (1994) Role of alpha 4-integrins in lymphocyte homing to mucosal tissues in vivo. J Immunol 152:3282–3293

    CAS  PubMed  Google Scholar 

  170. Wagner N, Lohler J, Kunkel EJ, Ley K, Leung E, Krissansen G, Rajewsky K, Muller W (1996) Critical role for beta7 integrins in formation of the gut-associated lymphoid tissue. Nature 382:366–370. doi:10.1038/382366a0

    Article  CAS  PubMed  Google Scholar 

  171. Wang C, McDonough JS, McDonald KG, Huang C, Newberry RD (2008) Alpha4beta7/MAdCAM-1 interactions play an essential role in transitioning cryptopatches into isolated lymphoid follicles and a nonessential role in cryptopatch formation. J Immunol 181:4052–4061

    CAS  PubMed  Google Scholar 

  172. Velaga S, Herbrand H, Friedrichsen M, Jiong T, Dorsch M, Hoffmann MW, Forster R, Pabst O (2009) Chemokine receptor CXCR5 supports solitary intestinal lymphoid tissue formation, B cell homing, and induction of intestinal IgA responses. J Immunol 182:2610–2619. doi:10.4049/jimmunol.0801141

    Article  CAS  PubMed  Google Scholar 

  173. McDonald KG, McDonough JS, Wang C, Kucharzik T, Williams IR, Newberry RD (2007) CC chemokine receptor 6 expression by B lymphocytes is essential for the development of isolated lymphoid follicles. Am J Pathol 170:1229–1240. doi:10.2353/ajpath.2007.060817

    Article  CAS  PubMed  Google Scholar 

  174. Bals R, Wang X, Meegalla RL, Wattler S, Weiner DJ, Nehls MC, Wilson JM (1999) Mouse beta-defensin 3 is an inducible antimicrobial peptide expressed in the epithelia of multiple organs. Infect Immun 67:3542–3547

    CAS  PubMed  Google Scholar 

  175. Yang D, Chertov O, Bykovskaia SN, Chen Q, Buffo MJ, Shogan J, Anderson M, Schroder JM, Wang JM, Howard OM, Oppenheim JJ (1999) Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science 286:525–528. doi:10.1126/science.286.5439.525

    Article  CAS  PubMed  Google Scholar 

  176. Newberry RD, McDonough JS, McDonald KG, Lorenz RG (2002) Postgestational lymphotoxin/lymphotoxin beta receptor interactions are essential for the presence of intestinal B lymphocytes. J Immunol 168:4988–4997

    CAS  PubMed  Google Scholar 

  177. Yamamoto M, Kweon MN, Rennert PD, Hiroi T, Fujihashi K, McGhee JR, Kiyono H (2004) Role of gut-associated lymphoreticular tissues in antigen-specific intestinal IgA immunity. J Immunol 173:762–769

    CAS  PubMed  Google Scholar 

  178. Mazmanian SK, Round JL, Kasper DL (2008) A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453:620–625. doi:10.1038/nature07008

    Article  CAS  PubMed  Google Scholar 

  179. Ohman L, Franzen L, Rudolph U, Birnbaumer L, Hornquist EH (2002) Regression of Peyer's patches in G alpha i2 deficient mice prior to colitis is associated with reduced expression of Bcl-2 and increased apoptosis. Gut 51:392–397. doi:10.1136/gut.51.3.392

    Article  CAS  PubMed  Google Scholar 

  180. Rudolph U, Finegold MJ, Rich SS, Harriman GR, Srinivasan Y, Brabet P, Boulay G, Bradley A, Birnbaumer L (1995) Ulcerative colitis and adenocarcinoma of the colon in G alpha i2-deficient mice. Nat Genet 10:143–150. doi:10.1038/ng0695-143

    Article  CAS  PubMed  Google Scholar 

  181. Wang Y, Zhang HX, Sun YP, Liu ZX, Liu XS, Wang L, Lu SY, Kong H, Liu QL, Li XH, Lu ZY, Chen SJ, Chen Z, Bao SS, Dai W, Wang ZG (2007) Rig-I−/− mice develop colitis associated with downregulation of G alpha i2. Cell Res 17:858–868. doi:10.1038/cr.2007.81

    Article  CAS  PubMed  Google Scholar 

  182. Spahn TW, Herbst H, Rennert PD, Lugering N, Maaser C, Kraft M, Fontana A, Weiner HL, Domschke W, Kucharzik T (2002) Induction of colitis in mice deficient of Peyer's patches and mesenteric lymph nodes is associated with increased disease severity and formation of colonic lymphoid patches. Am J Pathol 161:2273–2282

    PubMed  Google Scholar 

  183. Mackay F, Browning JL, Lawton P, Shah SA, Comiskey M, Bhan AK, Mizoguchi E, Terhorst C, Simpson SJ (1998) Both the lymphotoxin and tumor necrosis factor pathways are involved in experimental murine models of colitis. Gastroenterology 115:1464–1475. doi:10.1016/S0016-5085(98)70025-3

    Article  CAS  PubMed  Google Scholar 

  184. Dohi T, Rennert PD, Fujihashi K, Kiyono H, Shirai Y, Kawamura YI, Browning JL, McGhee JR (2001) Elimination of colonic patches with lymphotoxin beta receptor-Ig prevents Th2 cell-type colitis. J Immunol 167:2781–2790

    CAS  PubMed  Google Scholar 

  185. Gommerman JL, Browning JL (2003) Lymphotoxin/light, lymphoid microenvironments and autoimmune disease. Nat Rev Immunol 3:642–655. doi:10.1038/nri1151

    Article  CAS  PubMed  Google Scholar 

  186. Kaiserling E (2001) Newly-formed lymph nodes in the submucosa in chronic inflammatory bowel disease. Lymphology 34:22–29

    CAS  PubMed  Google Scholar 

  187. Connor EM, Eppihimer MJ, Morise Z, Granger DN, Grisham MB (1999) Expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in acute and chronic inflammation. J Leukoc Biol 65:349–355

    CAS  PubMed  Google Scholar 

  188. Feagan BG, Greenberg GR, Wild G, Fedorak RN, Pare P, McDonald JW, Dube R, Cohen A, Steinhart AH, Landau S, Aguzzi RA, Fox IH, Vandervoort MK (2005) Treatment of ulcerative colitis with a humanized antibody to the alpha4beta7 integrin. N Engl J Med 352:2499–2507. doi:10.1056/NEJMoa042982

    Article  CAS  PubMed  Google Scholar 

  189. van Assche G, Rutgeerts P (2002) Antiadhesion molecule therapy in inflammatory bowel disease. Inflamm Bowel Dis 8:291–300. doi:10.1097/00054725-200207000-00009

    Article  PubMed  Google Scholar 

  190. Carlsen HS, Baekkevold ES, Johansen FE, Haraldsen G, Brandtzaeg P (2002) B cell attracting chemokine 1 (CXCL13) and its receptor CXCR5 are expressed in normal and aberrant gut associated lymphoid tissue. Gut 51:364–371. doi:10.1136/gut.51.3.364

    Article  CAS  PubMed  Google Scholar 

  191. Luther SA, Lopez T, Bai W, Hanahan D, Cyster JG (2000) BLC expression in pancreatic islets causes B cell recruitment and lymphotoxin-dependent lymphoid neogenesis. Immunity 12:471–481. doi:10.1016/S1074-7613(00)80199-5

    Article  CAS  PubMed  Google Scholar 

  192. Ahern PP, Izcue A, Maloy KJ, Powrie F (2008) The interleukin-23 axis in intestinal inflammation. Immunol Rev 226:147–159. doi:10.1111/j.1600-065X.2008.00705.x

    Article  PubMed  Google Scholar 

  193. Mora JR, Bono MR, Manjunath N, Weninger W, Cavanagh LL, Rosemblatt M, Von Andrian UH (2003) Selective imprinting of gut-homing T cells by Peyer's patch dendritic cells. Nature 424:88–93. doi:10.1038/nature01726

    Article  CAS  PubMed  Google Scholar 

  194. Mucida D, Park Y, Kim G, Turovskaya O, Scott I, Kronenberg M, Cheroutre H (2007) Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science 317:256–260. doi:10.1126/science.1145697

    Article  CAS  PubMed  Google Scholar 

  195. Rimoldi M, Chieppa M, Salucci V, Avogadri F, Sonzogni A, Sampietro GM, Nespoli A, Viale G, Allavena P, Rescigno M (2005) Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells. Nat Immunol 6:507–514. doi:10.1038/ni1192

    Article  CAS  PubMed  Google Scholar 

  196. Taylor BC, Zaph C, Troy AE, Du Y, Guild KJ, Comeau MR, Artis D (2009) TSLP regulates intestinal immunity and inflammation in mouse models of helminth infection and colitis. J Exp Med 206:655–667. doi:10.1084/jem.20081499

    Article  CAS  PubMed  Google Scholar 

  197. Kato A, Favoreto S Jr, Avila PC, Schleimer RP (2007) TLR3- and Th2 cytokine-dependent production of thymic stromal lymphopoietin in human airway epithelial cells. J Immunol 179:1080–1087

    CAS  PubMed  Google Scholar 

  198. Lee HC, Ziegler SF (2007) Inducible expression of the proallergic cytokine thymic stromal lymphopoietin in airway epithelial cells is controlled by NFkappaB. Proc Natl Acad Sci U S A 104:914–919. doi:10.1073/pnas.0607305104

    Article  CAS  PubMed  Google Scholar 

  199. Klimpel GR, Chopra AK, Langley KE, Wypych J, Annable CA, Kaiserlian D, Ernst PB, Peterson JW (1995) A role for stem cell factor and c-kit in the murine intestinal tract secretory response to cholera toxin. J Exp Med 182:1931–1942. doi:10.1084/jem.182.6.1931

    Article  CAS  PubMed  Google Scholar 

  200. Watanabe M, Ueno Y, Yajima T, Iwao Y, Tsuchiya M, Ishikawa H, Aiso S, Hibi T, Ishii H (1995) Interleukin 7 is produced by human intestinal epithelial cells and regulates the proliferation of intestinal mucosal lymphocytes. J Clin Invest 95:2945–2953. doi:10.1172/JCI118002

    Article  CAS  PubMed  Google Scholar 

  201. Watanabe M, Ueno Y, Yajima T, Okamoto S, Hayashi T, Yamazaki M, Iwao Y, Ishii H, Habu S, Uehira M, Nishimoto H, Ishikawa H, Hata J, Hibi T (1998) Interleukin 7 transgenic mice develop chronic colitis with decreased interleukin 7 protein accumulation in the colonic mucosa. J Exp Med 187:389–402. doi:10.1084/jem.187.3.389

    Article  CAS  PubMed  Google Scholar 

  202. Totsuka T, Kanai T, Nemoto Y, Makita S, Okamoto R, Tsuchiya K, Watanabe M (2007) IL-7 Is essential for the development and the persistence of chronic colitis. J Immunol 178:4737–4748

    CAS  PubMed  Google Scholar 

  203. Tomita T, Kanai T, Nemoto Y, Totsuka T, Okamoto R, Tsuchiya K, Sakamoto N, Watanabe M (2008) Systemic, but not intestinal, IL-7 is essential for the persistence of chronic colitis. J Immunol 180:383–390

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The author sincerely apologizes to all colleagues whose work has been omitted due to space limitations. D.F. is supported by the Swiss National Science Foundation (SNF) grant PP00A-116894/1, the Mobiliar, and the Julia Bangerter Rhyner foundation. The author has no conflicting financial interest.

Author information

Authors and Affiliations

  1. Department of Biomedicine, Developmental Immunology, University of Basel, Mattenstrasse, 28, 4058, Basel, Switzerland

    Daniela Finke

Authors
  1. Daniela Finke
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daniela Finke.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Finke, D. Induction of intestinal lymphoid tissue formation by intrinsic and extrinsic signals. Semin Immunopathol 31, 151–169 (2009). https://doi.org/10.1007/s00281-009-0163-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00281-009-0163-6

Keywords

Search

Navigation