Abstract
Initially described as potent soluble mediators involved in inflammation, Tumour Necrosis Factor (TNF) and lymphotoxin alpha and beta (LTα/β) are now also appreciated as cardinal morphogenic regulators in secondary lymphoid organ formation, in addition to related activities of other members of the same TNF/LT family. Their developmental effects simultaneously show both substantial overlaps and remarkable tissue-specific differences. This part details the receptor–ligand relationship and developmental roles of those members of this large group of soluble or membrane-bound cytokines that have been associated with secondary lymphoid organ formation.
Keywords
- Tumour Necrosis Factor
- Lymphoid Organ
- Tumour Necrosis Factor Receptor
- Tumour Necrosis Factor Family
- Peripheral Lymphoid Organ
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References
Alimzhanov MB, Kuprash DV, Kosco-Vilbois MH, Luz A, Turetskaya RL, Tarakhovsky A, Rajewsky K, Nedospasov SA, Pfeffer K. (1997) Abnormal development of secondary lymphoid tissues in lymphotoxin beta-deficient mice. Proc Natl Acad Sci USA 94:9302–9307
Banks TA, Rouse BT, Kerley MK, Blair PJ, Godfrey VL, Kuklin NA, Bouley DM, Thomas J, Kanangat S, Mucenski ML (1995) Lymphotoxin-alpha-deficient mice. Effects on secondary lymphoid organ development and humoral immune responsiveness. J Immunol 155:1685–1693
Beutler B, Cerami A (1989) The biology of cachectin/TNF – a primary mediator of the host response. Annu Rev Immunol 7:625–655
Beutler B, Greenwald D, Hulmes JD, Chang M, Pan YC, Mathison J, Ulevitch R, Cerami A (1985) Identity of tumour necrosis factor and the macrophage-secreted factor cachectin. Nature 316:552–554
Bodmer JL, Schneider P, Tschopp J (2002) The molecular architecture of the TNF superfamily. Trends Biochem Sci 27:19–26
Brockhaus M, Schoenfeld HJ, Schlaeger EJ, Hunziker W, Lesslauer W, Loetscher H. (1990) Identification of two types of tumor necrosis factor receptors on human cell lines by monoclonal antibodies. Proc Natl Acad Sci USA 87:3127–3131
Browning JL, Ngam-ek A, Lawton P, DeMarinis J, Tizard R, Chow EP, Hession C, O’Brine-Greco B, Foley SF, Ware CF (1993) Lymphotoxin beta, a novel member of the TNF family that forms a heteromeric complex with lymphotoxin on the cell surface. Cell 72:847–56
Browning JL, Dougas I, Ngam-ek A, Bourdon PR, Ehrenfels BN, Miatkowski K, Zafari M, Yampaglia AM, Lawton P, Meier W et al (1995) Characterization of surface lymphotoxin forms. Use of specific monoclonal antibodies and soluble receptors. J Immunol 154:33–46
Cao Z, Xiong J, Takeuchi M, Kurama T, Goeddel DV (1996) TRAF6 is a signal transducer for interleukin-1. Nature 383:443–446
Cherfils-Vicini J, Vingert B, Varin A, Tartour E, Fridman WH, Sautès-Fridman C, Régnier CH, Cremer I. (2008) Characterization of immune functions in TRAF4-deficient mice. Immunology 124:562–574
Crowe PD, VanArsdale TL, Walter BN, Ware CF, Hession C, Ehrenfels B, Browning JL, Din WS, Goodwin RG, Smith CA (1994) A lymphotoxin-beta-specific receptor. Science 264:707–710
De Togni P, Goellner T, Ruddle NH, Streeter PR, Fick A, Mariathasan S, Smith SC, Carlson R, Shornick LP, Strauss-Schoenberger J, Russell JH, Karr R, Chaplin DD (1994) Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin. Science 264:703–707
Deonarain R, Verma A, Porter AC, Gewert DR, Platanias LC, Fish EN. (2003) Critical roles for IFN-beta in lymphoid development, myelopoiesis, and tumor development: links to tumor necrosis factor alpha. Proc Natl Acad Sci USA 100:13453–13458
Dougall WC, Glaccum M, Charrier K, Rohrbach K, Brasel K, De Smedt T, Daro E, Smith J, Tometsko ME, Maliszewski CR, Armstrong A, Shen V, Bain S, Cosman D, Anderson D, Morrissey PJ, Peschon JJ, Schuh J (1999) RANK is essential for osteoclast and lymph node development. Genes Dev 13:2412–2424
Eissner G, Kolch W, Scheurich P (2004) Ligands working as receptors: reverse signaling by members of the TNF superfamily enhance the plasticity of the immune system. Cytokine Growth Factor Rev 15:353–366
Fütterer 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
Gray PW, Aggarwal BB, Benton CV, Bringman TS, Henzel WJ, Jarrett JA, Leung DW, Moffat B, Ng P, Svedersky LP et al (1984) Cloning and expression of cDNA for human lymphotoxin, a lymphokine with tumour necrosis activity. Nature 312:721–724
Ha H, Han D, Choi Y (2009) TRAF-mediated TNFR-family signaling. Curr Protoc Immunol Nov;Chapter 11:Unit11.9D
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
Hohmann HP, Remy R, Pöschl B, van Loon AP (1990) Tumor necrosis factors-alpha and -beta bind to the same two types of tumor necrosis factor receptors and maximally activate the transcription factor NF-kappa B at low receptor occupancy and within minutes after receptor binding. J Biol Chem 265:15183–15188
Kim D, Mebius RE, MacMicking JD, Jung S, Cupedo T, Castellanos Y, Rho J, Wong BR, Josien R, Kim N, Rennert PD, Choi Y (2000) Regulation of peripheral lymph node genesis by the tumor necrosis factor family member TRANCE. J Exp Med 192:1467–1478
Kong YY, Yoshida H, Sarosi I, Tan HL, Timms E, Capparelli C, Morony S, Oliveira-dos-Santos AJ, Van G, Itie A, Khoo W, Wakeham A, Dunstan CR, Lacey DL, Mak TW, Boyle WJ, Penninger JM. (1999) OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature 397:315–323
Koni PA, Sacca R, Lawton P, Browning JL, Ruddle NH, Flavell RA. (1997) Distinct roles in lymphoid organogenesis for lymphotoxins alpha and beta revealed in lymphotoxin beta-deficient mice. Immunity 6:491–500
Kuprash DV, Alimzhanov MB, Tumanov AV, Grivennikov SI, Shakhov AN, Drutskaya LN, Marino MW, Turetskaya RL, Anderson AO, Rajewsky K, Pfeffer K, Nedospasov SA (2002) Redundancy in tumor necrosis factor (TNF) and lymphotoxin (LT) signaling in vivo: mice with inactivation of the entire TNF/LT locus versus single-knockout mice. Mol Cell Biol 22:8626–8634
Mauri DN, Ebner R, Montgomery RI, Kochel KD, Cheung TC, Yu GL, Ruben S, Murphy M, Eisenberg RJ, Cohen GH, Spear PG, Ware CF (1998) LIGHT, a new member of the TNF superfamily, and lymphotoxin alpha are ligands for herpesvirus entry mediator. Immunity 8:21–30
Müller U, Jongeneel CV, Nedospasov SA, Lindahl KF, Steinmetz M (1987) Tumour necrosis factor and lymphotoxin genes map close to H-2D in the mouse major histocompatibility complex. Nature 325:265–267
Naito A, Azuma S, Tanaka S, Miyazaki T, Takaki S, Takatsu K, Nakao K, Nakamura K, Katsuki M, Yamamoto T, Inoue J (1999) Severe osteopetrosis, defective interleukin-1 signalling and lymph node organogenesis in TRAF6-deficient mice. Genes Cells 4:353–362
Pasparakis M, Alexopoulou L, Episkopou V, Kollias G (1996) Immune and inflammatory responses in TNF alpha-deficient mice: a critical requirement for TNF alpha in the formation of primary B cell follicles, follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response. J Exp Med 184:1397–1411
Pasparakis M, Alexopoulou L, Grell M, Pfizenmaier K, Bluethmann H, Kollias G (1997) Peyer’s patch organogenesis is intact yet formation of B lymphocyte follicles is defective in peripheral lymphoid organs of mice deficient for tumor necrosis factor and its 55-kDa receptor. Proc Natl Acad Sci USA 94:6319–6323
Pennica D, Nedwin GE, Hayflick JS, Seeburg PH, Derynck R, Palladino MA, Kohr WJ, Aggarwal BB, Goeddel DV (1984) Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature 312:724–729
Pfeffer K (2003) Biological functions of tumor necrosis factor cytokines and their receptors. Cytokine Growth Factor Rev 14:185–191
Piao JH, Yoshida H, Yeh WC, Doi T, Xue X, Yagita H, Okumura K, Nakano H (2007) TNF receptor-associated factor 2-dependent canonical pathway is crucial for the development of Peyer’s patches. J Immunol 178:2272–2277
Pokholok DK, Maroulakou IG, Kuprash DV, Alimzhanov MB, Kozlov SV, Novobrantseva TI, Turetskaya RL, Green JE, Nedospasov SA (1995) Cloning and expression analysis of the murine lymphotoxin beta gene. Proc Natl Acad Sci USA 92:674–678
Qin J, Konno H, Ohshima D, Yanai H, Motegi H, Shimo Y, Hirota F, Matsumoto M, Takaki S, Inoue J, Akiyama T (2007) Developmental stage-dependent collaboration between the TNF receptor-associated factor 6 and lymphotoxin pathways for B cell follicle organization in secondary lymphoid organs. J Immunol 179:6799–6807
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
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
Scheu S, Alferink J, Pötzel T, Barchet W, Kalinke U, Pfeffer K (2002) Targeted disruption of LIGHT causes defects in costimulatory T cell activation and reveals cooperation with lymphotoxin beta in mesenteric lymph node genesis. J Exp Med 195:1613–1624
Sun M, Fink PJ (2007) A new class of reverse signaling costimulators belongs to the TNF family. J Immunol 179:4307–4312
Tumanov AV, Grivennikov SI, Shakhov AN, Rybtsov SA, Koroleva EP, Takeda J, Nedospasov SA, Kuprash DV (2003) Dissecting the role of lymphotoxin in lymphoid organs by conditional targeting. Immunol Rev 195:106–116
Vondenhoff MF, Greuter M, Goverse G, Elewaut D, Dewint P, Ware CF, Hoorweg K, Kraal G, Mebius RE (2009) LTbetaR signaling induces cytokine expression and up-regulates lymphangiogenic factors in lymph node anlagen. J Immunol 182:5439–5445
Ware CF (2008) Targeting lymphocyte activation through the lymphotoxin and LIGHT pathways. Immunol Rev 223:186–201
Ware CF, Crowe PD, Grayson MH, Androlewicz MJ, Browning JL (1992) Expression of surface lymphotoxin and tumor necrosis factor on activated T, B, and natural killer cells. J Immunol 149:3881–3888
Ware CF, VanArsdale TL, Crowe PD, Browning JL (1995) The ligands and receptors of the lymphotoxin system. Curr Top Microbiol Immunol 198:175–218
Williams-Abbott L, Walter BN, Cheung TC, Goh CR, Porter AG, Ware CF (1997) The Lymphotoxin-alpha (LTalpha) subunit is essential for the assembly, but not for the receptor specificity, of the membrane-anchored LTalpha 1beta 2 heterotrimeric ligand. J Biol Chem 272:19451–19456
Xie P, Stunz LL, Larison KD, Yang B, Bishop GA (2007) Tumor necrosis factor receptor-associated factor 3 is a critical regulator of B cell homeostasis in secondary lymphoid organs. Immunity 27:253–267
Xu Y, Cheng G, Baltimore D (1996) Targeted disruption of TRAF3 leads to postnatal lethality and defective T-dependent immune responses. Immunity 5:407–415
Yoshida H, Naito A, Inoue J, Satoh M, Santee-Cooper SM, Ware CF, Togawa A, Nishikawa S, 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
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Balogh, P. (2011). Lymphotoxin/Tumour Necrosis Factor Family Members as Morphogenic Factors. In: Balogh, P. (eds) Developmental Biology of Peripheral Lymphoid Organs. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-14429-5_3
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