Skip to main content

Advertisement

SpringerLink
Log in

Mucosal dendritic cell diversity in the gastrointestinal tract

  • Review
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

The discovery of dendritic cells (DCs) in skin by Paul Langerhans in 1868 identified a cell type which has since been recognized as a key link between innate and adaptive immunity. DCs originate from bone marrow and disseminate through blood to all tissues in the body, and distinct DC subpopulations have been identified in many different tissues. DC diversity is apparent throughout all mucosal surfaces of the body, but the focus of this review article is DC diversity throughout the gastro-intestinal tract (GIT). DC subpopulations have been well characterized in the oral cavity and small intestine, but DC characterization in other regions, such as the esophagus and stomach, is limited. Substantial research has focused on DC function during disease, but understanding the regulation of inflammation and the induction of acquired immune responses requires combined phenotypic and functional characterization of individual DC subpopulations. Furthermore, little is known regarding mucosal DC subpopulations in the GIT of the neonate and how these DC populations change following colonization by commensal microflora. The current review will highlight mucosal DC diversity and discuss factors that may influence mucosal DC differentiation.

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

Similar content being viewed by others

References

  • Agarwal S, Busse PJ (2010) Innate and adaptive immunosenescence. Ann Allergy Asthma Immunol 104(3):183–190, quiz 190-2, 210

    Article  CAS  PubMed  Google Scholar 

  • Allam JP et al (2003) Characterization of dendritic cells from human oral mucosa: a new Langerhans' cell type with high constitutive FcepsilonRI expression. J Allergy Clin Immunol 112(1):141–148

    Article  CAS  PubMed  Google Scholar 

  • Allam JP et al (2006) Comparative analysis of nasal and oral mucosa dendritic cells. Allergy 61(2):166–172

    Article  CAS  PubMed  Google Scholar 

  • Allam JP et al (2008) Distribution of Langerhans cells and mast cells within the human oral mucosa: new application sites of allergens in sublingual immunotherapy? Allergy 63(6):720–727

    Article  PubMed  Google Scholar 

  • Annacker O et al (2005) Essential role for CD103 in the T cell-mediated regulation of experimental colitis. J Exp Med 202(8):1051–1061

    Article  CAS  PubMed  Google Scholar 

  • Asselin-Paturel C et al (2003) Mouse strain differences in plasmacytoid dendritic cell frequency and function revealed by a novel monoclonal antibody. J Immunol 171(12):6466–6477

    CAS  PubMed  Google Scholar 

  • Atarashi K et al (2008) ATP drives lamina propria T(H)17 cell differentiation. Nature 455(7214):808–812

    Article  CAS  PubMed  Google Scholar 

  • Becker Y (2003) Milestones in the research on skin epidermal Langerhans/dendritic cells (LCs/DCs) from the discovery of Paul Langerhans 1868-1989. Virus Genes 26(2):131–134

    Article  CAS  PubMed  Google Scholar 

  • Bell SJ et al (2001) Migration and maturation of human colonic dendritic cells. J Immunol 166(8):4958–4967

    CAS  PubMed  Google Scholar 

  • Bilsborough J et al (2003) Mucosal CD8alpha + DC, with a plasmacytoid phenotype, induce differentiation and support function of T cells with regulatory properties. Immunology 108(4):481–492

    Article  CAS  PubMed  Google Scholar 

  • Bimczok D et al (2005) Site-specific expression of CD11b and SIRPalpha (CD172a) on dendritic cells: implications for their migration patterns in the gut immune system. Eur J Immunol 35(5):1418–1427

    Article  CAS  PubMed  Google Scholar 

  • Birbeck MS, Breathnach AS, Everell JD (1960/1961) An electron microscope study of basal melanocytes and high-level clear cells (Langherans cells) in Vitiligo. J Investig Dermatol 37:51–64

    Article  Google Scholar 

  • Bobryshev YV et al (2009a) Dendritic cell-associated immune inflammation of cardiac mucosa: a possible factor in the formation of Barrett's esophagus. J Gastrointest Surg 13(3):442–450

    Article  PubMed  Google Scholar 

  • Bobryshev YV et al (2009b) Dendritic cells in Barrett's esophagus and esophageal adenocarcinoma. J Gastrointest Surg 13(1):44–53

    Article  PubMed  Google Scholar 

  • Caux C et al (1992) GM-CSF and TNF-alpha cooperate in the generation of dendritic Langerhans cells. Nature 360(6401):258–261

    Article  CAS  PubMed  Google Scholar 

  • Cruickshank SM et al (2005) Characterization of colonic dendritic cells in normal and colitic mice. World J Gastroenterol 11(40):6338–6347

    PubMed  Google Scholar 

  • D'Amico A, Wu L (2003) The early progenitors of mouse dendritic cells and plasmacytoid predendritic cells are within the bone marrow hemopoietic precursors expressing Flt3. J Exp Med 198(2):293–303

    Article  PubMed  Google Scholar 

  • del Rio ML et al (2010) Development and functional specialization of CD103+ dendritic cells. Immunol Rev 234(1):268–281

    Article  PubMed  Google Scholar 

  • Dellmann H-D, Brown EM (1987) Textbook of veterinary histology, 3rd edn. Lea & Febiger, Philadelphia

    Google Scholar 

  • Desai A, Grolleau-Julius A, Yung R (2010) Leukocyte function in the aging immune system. J Leukoc Biol 87(6):1001–1009

    Article  CAS  PubMed  Google Scholar 

  • Egeler RM, Zantinga AR, Coppes MJ, Langerhans P Jr (1994) (1847-1888): a short life, yet two eponymic legacies. Med Pediatr Oncol 22(2):129–132

    Article  CAS  PubMed  Google Scholar 

  • Escribano C, Delgado-Martin C, Rodriguez-Fernandez JL (2009) CCR7-dependent stimulation of survival in dendritic cells involves inhibition of GSK3beta. J Immunol 183(10):6282–6295

    Article  CAS  PubMed  Google Scholar 

  • Felaco P et al (2009) Infections and mast cells. J Biol Regul Homeost Agents 23(4):231–238

    CAS  PubMed  Google Scholar 

  • Feng P et al (2009) Immune cells of the human peripheral taste system: dominant dendritic cells and CD4 T cells. Brain Behav Immun 23(6):760–766

    Article  CAS  PubMed  Google Scholar 

  • Fortin G et al (2009) A role for CD47 in the development of experimental colitis mediated by SIRPalpha + CD103- dendritic cells. J Exp Med 206(9):1995–2011

    Article  CAS  PubMed  Google Scholar 

  • Geissmann F et al (2008) Development of monocytes, macrophages, and dendritic cells. Science 327(5966):656–661

    Article  Google Scholar 

  • Griebel PJ, Hein WR (1996) Expanding the role of Peyer's patches in B-cell ontogeny. Immunol Today 17(1):30–39

    Article  CAS  PubMed  Google Scholar 

  • Halleraker M, Landsverk T, Nicander L (1990) Organization of ruminant Peyer's patches as seen with enzyme histochemical markers of stromal and accessory cells. Vet Immunol Immunopathol 26(1):93–104

    Article  CAS  PubMed  Google Scholar 

  • Hart AL et al (2005) Characteristics of intestinal dendritic cells in inflammatory bowel diseases. Gastroenterology 129(1):50–65

    Article  CAS  PubMed  Google Scholar 

  • Hausmann M et al (2002) Toll-like receptors 2 and 4 are up-regulated during intestinal inflammation. Gastroenterology 122(7):1987–2000

    Article  CAS  PubMed  Google Scholar 

  • Inaba K et al (1992) Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J Exp Med 176(6):1693–1702

    Article  CAS  PubMed  Google Scholar 

  • Iwasaki A (2007) Mucosal dendritic cells. Annu Rev Immunol 25:381–418

    Article  CAS  PubMed  Google Scholar 

  • 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(8):1381–1394

    Article  CAS  PubMed  Google Scholar 

  • Iwasaki A, Kelsall BL (2001) Unique functions of CD11b+, CD8 alpha+, and double-negative Peyer's patch dendritic cells. J Immunol 166(8):4884–4890

    CAS  PubMed  Google Scholar 

  • Jaensson E et al (2008) Small intestinal CD103+ dendritic cells display unique functional properties that are conserved between mice and humans. J Exp Med 205(9):2139–2149

    Article  CAS  PubMed  Google Scholar 

  • Jameson B et al (2002) Expression of DC-SIGN by dendritic cells of intestinal and genital mucosae in humans and rhesus macaques. J Virol 76(4):1866–1875

    Article  CAS  PubMed  Google Scholar 

  • Jarrossay D et al (2001) Specialization and complementarity in microbial molecule recognition by human myeloid and plasmacytoid dendritic cells. Eur J Immunol 31(11):3388–3393

    Article  CAS  PubMed  Google Scholar 

  • Johansson-Lindbom B et al (2005) Functional specialization of gut CD103+ dendritic cells in the regulation of tissue-selective T cell homing. J Exp Med 202(8):1063–1073

    Article  CAS  PubMed  Google Scholar 

  • Josefsen TD, Landsverk T (1996) T cell subsets and Langerhans cells in the forestomach mucosa of adult sheep and sheep foetuses. Vet Immunol Immunopathol 51(1–2):101–111

    Article  CAS  PubMed  Google Scholar 

  • Kalinski P et al (1997) IL-12-deficient dendritic cells, generated in the presence of prostaglandin E2, promote type 2 cytokine production in maturing human naive T helper cells. J Immunol 159(1):28–35

    CAS  PubMed  Google Scholar 

  • Kao JY et al (2006) Helicobacter pylori-secreted factors inhibit dendritic cell IL-12 secretion: a mechanism of ineffective host defense. Am J Physiol Gastrointest Liver Physiol 291(1):G73–G81

    Article  CAS  PubMed  Google Scholar 

  • Keita AV et al (2008) Increased uptake of non-pathogenic E. coli via the follicle-associated epithelium in longstanding ileal Crohn's disease. J Pathol 215(2):135–144

    Article  CAS  PubMed  Google Scholar 

  • Kelsall BL, Strober W (1996) Distinct populations of dendritic cells are present in the subepithelial dome and T cell regions of the murine Peyer's patch. J Exp Med 183(1):237–247

    Article  CAS  PubMed  Google Scholar 

  • Khamri W et al (2010) Helicobacter pylori stimulates dendritic cells to induce interleukin-17 expression from CD4+ T lymphocytes. Infect Immun 78(2):845–853

    Article  CAS  PubMed  Google Scholar 

  • Krajina T et al (2003) Colonic lamina propria dendritic cells in mice with CD4+ T cell-induced colitis. Eur J Immunol 33(4):1073–1083

    Article  CAS  PubMed  Google Scholar 

  • Liu K et al (2009) In vivo analysis of dendritic cell development and homeostasis. Science 324(5925):392–397

    CAS  PubMed  Google Scholar 

  • MacDonald KP et al (2005) The colony-stimulating factor 1 receptor is expressed on dendritic cells during differentiation and regulates their expansion. J Immunol 175(3):1399–1405

    CAS  PubMed  Google Scholar 

  • Malmstrom V et al (2001) CD134L expression on dendritic cells in the mesenteric lymph nodes drives colitis in T cell-restored SCID mice. J Immunol 166(11):6972–6981

    CAS  PubMed  Google Scholar 

  • Mascarell L et al (2008) Oral dendritic cells mediate antigen-specific tolerance by stimulating TH1 and regulatory CD4+ T cells. J Allergy Clin Immunol 122(3):603–609, e5

    Article  CAS  PubMed  Google Scholar 

  • Middel P et al (2006) Increased number of mature dendritic cells in Crohn's disease: evidence for a chemokine mediated retention mechanism. Gut 55(2):220–227

    Article  CAS  PubMed  Google Scholar 

  • Monteleone I et al (2008) IL-10-dependent partial refractoriness to Toll-like receptor stimulation modulates gut mucosal dendritic cell function. Eur J Immunol 38(6):1533–1547

    Article  CAS  PubMed  Google Scholar 

  • Mowat AM (2003) Anatomical basis of tolerance and immunity to intestinal antigens. Nat Rev Immunol 3(4):331–341

    Article  CAS  PubMed  Google Scholar 

  • Mutwiri G et al (1999) Ileal and jejunal Peyer's patches play distinct roles in mucosal immunity of sheep. Immunology 97(3):455–461

    Article  CAS  PubMed  Google Scholar 

  • Naik SH et al (2007) Development of plasmacytoid and conventional dendritic cell subtypes from single precursor cells derived in vitro and in vivo. Nat Immunol 8(11):1217–1226

    Article  CAS  PubMed  Google Scholar 

  • Necchi V et al (2009) Evidence for transepithelial dendritic cells in human H. pylori active gastritis. Helicobacter 14(3):208–222

    Article  CAS  PubMed  Google Scholar 

  • Niess JH (2008) Role of mucosal dendritic cells in inflammatory bowel disease. World J Gastroenterol 14(33):5138–5148

    Article  CAS  PubMed  Google Scholar 

  • Niess JH et al (2005) CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science 307(5707):254–258

    Article  CAS  PubMed  Google Scholar 

  • Nishi T et al (2003) Involvement of myeloid dendritic cells in the development of gastric secondary lymphoid follicles in Helicobacter pylori-infected neonatally thymectomized BALB/c mice. Infect Immun 71(4):2153–2162

    Article  CAS  PubMed  Google Scholar 

  • Press CM, Halleraker M, Landsverk T (1992) Ontogeny of leukocyte populations in the ileal Peyer's patch of sheep. Dev Comp Immunol 16(2–3):229–241

    Article  CAS  PubMed  Google Scholar 

  • Rakoff-Nahoum S, Medzhitov R (2006) Role of the innate immune system and host-commensal mutualism. Curr Top Microbiol Immunol 308:1–18

    Article  CAS  PubMed  Google Scholar 

  • Reizis B (2010) Regulation of plasmacytoid dendritic cell development. Curr Opin Immunol 22(2):206–211

    Article  CAS  PubMed  Google Scholar 

  • Rescigno M, Di Sabatino A (2009) Dendritic cells in intestinal homeostasis and disease. J Clin Invest 119(9):2441–2450

    Article  CAS  PubMed  Google Scholar 

  • Rescigno M et al (2001) Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol 2(4):361–367

    Article  CAS  PubMed  Google Scholar 

  • Rimoldi M et al (2005) Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells. Nat Immunol 6(5):507–514

    Article  CAS  PubMed  Google Scholar 

  • Salim SY et al (2009) CD83 + CCR7- dendritic cells accumulate in the subepithelial dome and internalize translocated Escherichia coli HB101 in the Peyer's patches of ileal Crohn's disease. Am J Pathol 174(1):82–90

    Article  CAS  PubMed  Google Scholar 

  • Sallusto F, Lanzavecchia A (1994) Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J Exp Med 179(4):1109–1118

    Article  CAS  PubMed  Google Scholar 

  • Sallusto F et al (1995) Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: downregulation by cytokines and bacterial products. J Exp Med 182(2):389–400

    Article  CAS  PubMed  Google Scholar 

  • Shortman K, Liu YJ (2002) Mouse and human dendritic cell subtypes. Nat Rev Immunol 2(3):151–161

    Article  CAS  PubMed  Google Scholar 

  • Stein HJ, Siewert JR (1993) Barrett's esophagus: pathogenesis, epidemiology, functional abnormalities, malignant degeneration, and surgical management. Dysphagia 8(3):276–288

    Article  CAS  PubMed  Google Scholar 

  • Steinman RM, Cohn ZA (1973) Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J Exp Med 137(5):1142–1162

    Article  CAS  PubMed  Google Scholar 

  • Steinman RM, Cohn ZA (1974) Identification of a novel cell type in peripheral lymphoid organs of mice. II. Functional properties in vitro. J Exp Med 139(2):380–397

    Article  CAS  PubMed  Google Scholar 

  • Steinman RM, Lustig DS, Cohn ZA (1974) Identification of a novel cell type in peripheral lymphoid organs of mice. 3. Functional properties in vivo. J Exp Med 139(6):1431–1445

    Article  CAS  PubMed  Google Scholar 

  • Steinman RM, Adams JC, Cohn ZA (1975) Identification of a novel cell type in peripheral lymphoid organs of mice. IV. Identification and distribution in mouse spleen. J Exp Med 141(4):804–820

    CAS  PubMed  Google Scholar 

  • Steinman RM et al (1979) Identification of a novel cell type in peripheral lymphoid organs of mice. V. Purification of spleen dendritic cells, new surface markers, and maintenance in vitro. J Exp Med 149(1):1–16

    Article  CAS  PubMed  Google Scholar 

  • Sun CM et al (2007) Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid. J Exp Med 204(8):1775–1785

    Article  CAS  PubMed  Google Scholar 

  • Takenaka S et al (2007) Dendritic cells derived from murine colonic mucosa have unique functional and phenotypic characteristics. J Immunol 178(12):7984–7993

    CAS  PubMed  Google Scholar 

  • Taniguchi Y et al (2009) Mechanism for maintaining homeostasis in the immune system of the intestine. Anticancer Res 29(11):4855–4860

    CAS  PubMed  Google Scholar 

  • te Velde AA et al (2003) Increased expression of DC-SIGN + IL-12 + IL-18+ and CD83 + IL-12-IL-18- dendritic cell populations in the colonic mucosa of patients with Crohn's disease. Eur J Immunol 33(1):143–151

    Article  CAS  PubMed  Google Scholar 

  • Tezuka H, Ohteki T (2010) Regulation of intestinal homeostasis by dendritic cells. Immunol Rev 234(1):247–258

    Article  CAS  PubMed  Google Scholar 

  • Travis MA et al (2007) Loss of integrin alpha(v)beta8 on dendritic cells causes autoimmunity and colitis in mice. Nature 449(7160):361–365

    Article  CAS  PubMed  Google Scholar 

  • Tsang CH (2007) In utero oral DNA immunization: induction of specific immunity in the second trimester ovine fetus, in veterinary microbiology. University of Saskatchewan, Saskatoon

    Google Scholar 

  • Uematsu S et al (2008) Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5. Nat Immunol 9(7):769–776

    Article  CAS  PubMed  Google Scholar 

  • Varol C et al (2007) Monocytes give rise to mucosal, but not splenic, conventional dendritic cells. J Exp Med 204(1):171–180

    Article  CAS  PubMed  Google Scholar 

  • Varol C et al (2009) Intestinal lamina propria dendritic cell subsets have different origin and functions. Immunity 31(3):502–512

    Article  CAS  PubMed  Google Scholar 

  • Wang YH et al (2010) Helicobacter pylori impairs murine dendritic cell responses to infection. PLoS One 5(5):e10844

    Article  PubMed  Google Scholar 

  • Zuniga EI et al (2004) Bone marrow plasmacytoid dendritic cells can differentiate into myeloid dendritic cells upon virus infection. Nat Immunol 5(12):1227–1234

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Vaccine and Infectious Disease Organization, University of Saskatchewan, 120 Veterinary Road, Saskatoon, SK, S7N 5E3, Canada

    Patrick N. Fries & Philip J. Griebel

  2. School of Public Health, University of Saskatchewan, Saskatoon, SK, S7N 5E3, Canada

    Philip J. Griebel

Authors
  1. Patrick N. Fries
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Philip J. Griebel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Philip J. Griebel.

Additional information

Philip Griebel

is a holder of a Tier I CRC in Neonatal Mucosal Immunology and Patrick Fries is funded by Genome Canada. This article is published with the permission of the Director of VIDO as manuscript #585.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fries, P.N., Griebel, P.J. Mucosal dendritic cell diversity in the gastrointestinal tract. Cell Tissue Res 343, 33–41 (2011). https://doi.org/10.1007/s00441-010-1030-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-010-1030-4

Keywords

Search

Navigation