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Gene Review

Ltbr  -  lymphotoxin B receptor

Mus musculus

Synonyms: AI256028, CD18, LT beta-R, LT-beta receptor, LTbetaR, ...
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Disease relevance of Ltbr


Psychiatry related information on Ltbr


High impact information on Ltbr

  • The phenotypes of aly/aly mice are more severe than those of Ltbr-/- mice, however, indicating involvement of Nik in signal transduction mediated by other receptors [7].
  • Of the several families of adhesion receptors involved in leukocyte-endothelial cell interactions, only the selectins have been shown to initiate leukocyte interaction under physiologic shear; indeed, beta 2 (CD18) intergrins responsible for neutrophil arrest are unable to engage without prior selectin-mediated rolling [8].
  • CD18-deficient (Itgb2(-/-)) T cells showed largely normal in vitro function [9].
  • To understand the integrin requirements of T-helper (T(H)) effector subsets, we investigated the contribution of CD18 (beta(2) integrin) to T(H)1 and T(H)2 function in vitro and in relevant disease models [9].
  • Extraintestinal dissemination of Salmonella by CD18-expressing phagocytes [10].

Chemical compound and disease context of Ltbr

  • We demonstrate that a T cell-restricted ligand, homologous to lymphotoxin, exhibits inducible expression, competes with herpesvirus glycoprotein D for herpesvirus entry mediator on T cells (LIGHT), signaling through the lymphotoxin receptor (LTbetaR) expressed on mature hepatocytes induces massive hepatomegaly [11].
  • These results suggest the importance of beta2 integrin (CD11/CD18) as a cellular receptor of P. gingivalis fimbriae in the initiation stage of the pathogenic mechanism of the organism in periodontal disease [12].
  • LIGHT is a member of the tumor necrosis factor (TNF) superfamily, and its function is mediated by at least two receptors, including lymphotoxin beta receptor (LTbetaR) and herpes simplex virus entry mediator [13].
  • However, when ICAM-1-, but not CD18-, deficient mice were pretreated with fucoidin, the adverse effects of PAF were markedly reduced; survival was 100%, although hypotension still developed [14].

Biological context of Ltbr


Anatomical context of Ltbr


Associations of Ltbr with chemical compounds

  • Since signaling through other members of this receptor family can induce cell death, e.g., the TNF and Fas receptors, it is important to determine if similar signaling events can be communicated via the LT-beta-R [1].
  • Loss of LTbeta and LTbeta receptor signaling reduced the number of oval cells expressing A6 and muscle pyruvate kinase [21].
  • Lung injury after deposition of IgA immune complexes. Requirements for CD18 and L-arginine [22].
  • To investigate LTbetaR-specific mast cell activation, the LTbetaR on BMMC from either wild-type or LTbetaR-deficient mice was stimulated with recombinant mouse LIGHT or agonistic mAbs in the presence of ionomycin [23].
  • These results indicate that CD18 is critically involved in vivo in activating leukocytes to produce cytokines in response to LPS [24].

Physical interactions of Ltbr


Regulatory relationships of Ltbr


Other interactions of Ltbr


Analytical, diagnostic and therapeutic context of Ltbr


  1. Signaling through the lymphotoxin beta receptor induces the death of some adenocarcinoma tumor lines. Browning, J.L., Miatkowski, K., Sizing, I., Griffiths, D., Zafari, M., Benjamin, C.D., Meier, W., Mackay, F. J. Exp. Med. (1996) [Pubmed]
  2. The lymphotoxin beta receptor is critically involved in controlling infections with the intracellular pathogens Mycobacterium tuberculosis and Listeria monocytogenes. Ehlers, S., Hölscher, C., Scheu, S., Tertilt, C., Hehlgans, T., Suwinski, J., Endres, R., Pfeffer, K. J. Immunol. (2003) [Pubmed]
  3. A role for lymphotoxin beta receptor in host defense against Mycobacterium bovis BCG infection. Lucas, R., Tacchini-Cottier, F., Guler, R., Vesin, D., Jemelin, S., Olleros, M.L., Marchal, G., Browning, J.L., Vassalli, P., Garcia, I. Eur. J. Immunol. (1999) [Pubmed]
  4. Suppression of established experimental autoimmune encephalomyelitis and formation of meningeal lymphoid follicles by lymphotoxin beta receptor-Ig fusion protein. Columba-Cabezas, S., Griguoli, M., Rosicarelli, B., Magliozzi, R., Ria, F., Serafini, B., Aloisi, F. J. Neuroimmunol. (2006) [Pubmed]
  5. Activation of the lymphotoxin-beta receptor induces NFkappaB-dependent interleukin-6 and MIP-2 secretion in mouse fibrosarcoma cells. Hehlgans, T., Müller, P., Stopfer, P., Männel, D.N. Eur. Cytokine Netw. (2003) [Pubmed]
  6. Flow cytometric patterns in blood from dogs with non-neoplastic and neoplastic hematologic diseases using double labeling for CD18 and CD45. Comazzi, S., Gelain, M.E., Spagnolo, V., Riondato, F., Guglielmino, R., Sartorelli, P. Veterinary clinical pathology / American Society for Veterinary Clinical Pathology. (2006) [Pubmed]
  7. Alymphoplasia is caused by a point mutation in the mouse gene encoding Nf-kappa b-inducing kinase. Shinkura, R., Kitada, K., Matsuda, F., Tashiro, K., Ikuta, K., Suzuki, M., Kogishi, K., Serikawa, T., Honjo, T. Nat. Genet. (1999) [Pubmed]
  8. alpha 4 integrins mediate lymphocyte attachment and rolling under physiologic flow. Berlin, C., Bargatze, R.F., Campbell, J.J., von Andrian, U.H., Szabo, M.C., Hasslen, S.R., Nelson, R.D., Berg, E.L., Erlandsen, S.L., Butcher, E.C. Cell (1995) [Pubmed]
  9. Differential requirement for CD18 in T-helper effector homing. Lee, S.H., Prince, J.E., Rais, M., Kheradmand, F., Shardonofsky, F., Lu, H., Beaudet, A.L., Smith, C.W., Soong, L., Corry, D.B. Nat. Med. (2003) [Pubmed]
  10. Extraintestinal dissemination of Salmonella by CD18-expressing phagocytes. Vazquez-Torres, A., Jones-Carson, J., Bäumler, A.J., Falkow, S., Valdivia, R., Brown, W., Le, M., Berggren, R., Parks, W.T., Fang, F.C. Nature (1999) [Pubmed]
  11. Contribution of the lymphotoxin beta receptor to liver regeneration. Anders, R.A., Subudhi, S.K., Wang, J., Pfeffer, K., Fu, Y.X. J. Immunol. (2005) [Pubmed]
  12. Porphyromonas gingivalis fimbriae use beta2 integrin (CD11/CD18) on mouse peritoneal macrophages as a cellular receptor, and the CD18 beta chain plays a functional role in fimbrial signaling. Takeshita, A., Murakami, Y., Yamashita, Y., Ishida, M., Fujisawa, S., Kitano, S., Hanazawa, S. Infect. Immun. (1998) [Pubmed]
  13. TRAF2 plays a key, nonredundant role in LIGHT-lymphotoxin beta receptor signaling. Kim, Y.S., Nedospasov, S.A., Liu, Z.G. Mol. Cell. Biol. (2005) [Pubmed]
  14. P-selectin-deficient mice are protected from PAF-induced shock, intestinal injury, and lethality. Sun, X., Rozenfeld, R.A., Qu, X., Huang, W., Gonzalez-Crussi, F., Hsueh, W. Am. J. Physiol. (1997) [Pubmed]
  15. Lymphotoxin pathway-directed, autoimmune regulator-independent central tolerance to arthritogenic collagen. Chin, R.K., Zhu, M., Christiansen, P.A., Liu, W., Ware, C., Peltonen, L., Zhang, X., Guo, L., Han, S., Zheng, B., Fu, Y.X. J. Immunol. (2006) [Pubmed]
  16. Mouse lymphotoxin-beta receptor. Molecular genetics, ligand binding, and expression. Force, W.R., Walter, B.N., Hession, C., Tizard, R., Kozak, C.A., Browning, J.L., Ware, C.F. J. Immunol. (1995) [Pubmed]
  17. The lymphotoxin beta receptor controls organogenesis and affinity maturation in peripheral lymphoid tissues. Fütterer, A., Mink, K., Luz, A., Kosco-Vilbois, M.H., Pfeffer, K. Immunity (1998) [Pubmed]
  18. The lymphotoxin-beta receptor induces different patterns of gene expression via two NF-kappaB pathways. Dejardin, E., Droin, N.M., Delhase, M., Haas, E., Cao, Y., Makris, C., Li, Z.W., Karin, M., Ware, C.F., Green, D.R. Immunity (2002) [Pubmed]
  19. Lymph node genesis is induced by signaling through the lymphotoxin beta receptor. Rennert, P.D., James, D., Mackay, F., Browning, J.L., Hochman, P.S. Immunity (1998) [Pubmed]
  20. Mature follicular dendritic cell networks depend on expression of lymphotoxin beta receptor by radioresistant stromal cells and of lymphotoxin beta and tumor necrosis factor by B cells. Endres, R., Alimzhanov, M.B., Plitz, T., Fütterer, A., Kosco-Vilbois, M.H., Nedospasov, S.A., Rajewsky, K., Pfeffer, K. J. Exp. Med. (1999) [Pubmed]
  21. Differential lymphotoxin-beta and interferon gamma signaling during mouse liver regeneration induced by chronic and acute injury. Akhurst, B., Matthews, V., Husk, K., Smyth, M.J., Abraham, L.J., Yeoh, G.C. Hepatology (2005) [Pubmed]
  22. Lung injury after deposition of IgA immune complexes. Requirements for CD18 and L-arginine. Mulligan, M.S., Warren, J.S., Smith, C.W., Anderson, D.C., Yeh, C.G., Rudolph, A.R., Ward, P.A. J. Immunol. (1992) [Pubmed]
  23. Lymphotoxin-beta receptor activation by activated T cells induces cytokine release from mouse bone marrow-derived mast cells. Stopfer, P., Männel, D.N., Hehlgans, T. J. Immunol. (2004) [Pubmed]
  24. Prevention of endotoxin-induced acute lethality in Propionibacterium acnes-primed rabbits by an antibody to leukocyte integrin beta 2 with concomitant reduction of cytokine production. Ikeda, N., Mukaida, N., Kaneko, S., Fujioka, N., Su, S., Nariuchi, H., Unoura, M., Harada, K., Nakanuma, Y., Kobayashi, K. Infect. Immun. (1995) [Pubmed]
  25. The complementation of lymphotoxin deficiency with LIGHT, a newly discovered TNF family member, for the restoration of secondary lymphoid structure and function. Wang, J., Foster, A., Chin, R., Yu, P., Sun, Y., Wang, Y., Pfeffer, K., Fu, Y.X. Eur. J. Immunol. (2002) [Pubmed]
  26. Both the lymphotoxin and tumor necrosis factor pathways are involved in experimental murine models of colitis. Mackay, F., Browning, J.L., Lawton, P., Shah, S.A., Comiskey, M., Bhan, A.K., Mizoguchi, E., Terhorst, C., Simpson, S.J. Gastroenterology (1998) [Pubmed]
  27. Thymic medullary epithelial cell differentiation, thymocyte emigration, and the control of autoimmunity require lympho-epithelial cross talk via LTbetaR. Boehm, T., Scheu, S., Pfeffer, K., Bleul, C.C. J. Exp. Med. (2003) [Pubmed]
  28. Transit time of leukocytes rolling through venules controls cytokine-induced inflammatory cell recruitment in vivo. Jung, U., Norman, K.E., Scharffetter-Kochanek, K., Beaudet, A.L., Ley, K. J. Clin. Invest. (1998) [Pubmed]
  29. Blocking lymphotoxin-beta receptor activation diminishes inflammation via reduced mucosal addressin cell adhesion molecule-1 (MAdCAM-1) expression and leucocyte margination in chronic DSS-induced colitis. Stopfer, P., Obermeier, F., Dunger, N., Falk, W., Farkas, S., Janotta, M., Möller, A., Männel, D.N., Hehlgans, T. Clin. Exp. Immunol. (2004) [Pubmed]
  30. Differentiation of follicular dendritic cells and full antibody responses require tumor necrosis factor receptor-1 signaling. Le Hir, M., Bluethmann, H., Kosco-Vilbois, M.H., Müller, M., di Padova, F., Moore, M., Ryffel, B., Eugster, H.P. J. Exp. Med. (1996) [Pubmed]
  31. RelB is required for Peyer's patch development: differential regulation of p52-RelB by lymphotoxin and TNF. Yilmaz, Z.B., Weih, D.S., Sivakumar, V., Weih, F. EMBO J. (2003) [Pubmed]
  32. Ly49 and CD94/NKG2 receptor acquisition by NK cells does not require lymphotoxin-beta receptor expression. Stevenaert, F., Van Beneden, K., De Colvenaer, V., Franki, A.S., Debacker, V., Boterberg, T., Deforce, D., Pfeffer, K., Plum, J., Elewaut, D., Leclercq, G. Blood (2005) [Pubmed]
  33. Visualization of lymphotoxin-beta and lymphotoxin-beta receptor expression in mouse embryos. Browning, J.L., French, L.E. J. Immunol. (2002) [Pubmed]
  34. Defective lymphotoxin-beta receptor-induced NF-kappaB transcriptional activity in NIK-deficient mice. Yin, L., Wu, L., Wesche, H., Arthur, C.D., White, J.M., Goeddel, D.V., Schreiber, R.D. Science (2001) [Pubmed]
  35. Intrinsic lymphotoxin-beta receptor requirement for homeostasis of lymphoid tissue dendritic cells. Kabashima, K., Banks, T.A., Ansel, K.M., Lu, T.T., Ware, C.F., Cyster, J.G. Immunity (2005) [Pubmed]
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