The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Tnfsf4  -  tumor necrosis factor (ligand) superfamily...

Mus musculus

Synonyms: Ath-1, Ath1, CD134L, OX-40L, OX40 ligand, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Tnfsf4


High impact information on Tnfsf4


Chemical compound and disease context of Tnfsf4

  • To test whether OX40/OX40L interaction plays a role in chronic intestinal inflammation, we induced chronic colitis using dextran sulfate sodium and treated the mice with a murine fusion protein (OX40-IgG) [10].
  • A mouse cytomegalovirus glycoprotein, gp34, forms a complex with folded class I MHC molecules in the ER which is not retained but is transported to the cell surface [11].

Biological context of Tnfsf4

  • Ath-1 maps on chromosome 1 near Alp-2, a gene that determines the structure of apolipoprotein A-II, one of the two major proteins found in HDL [12].
  • The affinity and kinetics of the OX40L/OX40 interactions were studied using the BIAcoreTM biosensor, which measures macromolecular interactions in real time [13].
  • However, somewhat paradoxically, the initial activation of T cells responsive to islet beta cell Ag was slightly faster and more efficient in the absence of OX40L, with an increased degree of cell proliferation and survival in the deficient hosts [3].
  • The present results orchestrated in this study indicate that OX40/OX40L interaction may be a vital link in our understanding of T cell-mediated organ-specific autoimmunity [14].
  • A necessary role for OX40 in the development and homeostasis of Treg cells can be inferred from the reduced numbers of the cells present in the spleens of OX40-deficient mice, and their elevated numbers in the spleens of mice that overexpress the OX40 ligand (OX40L) [15].

Anatomical context of Tnfsf4


Associations of Tnfsf4 with chemical compounds

  • Recent in vitro studies have established that activated B cells express OX40 ligand (L), a member of the tumor necrosis factor/nerve growth factor family of cytokines, and become stimulated to proliferate and secrete immunoglobulin (Ig) after cross-linking of OX40L by its counterreceptor OX40, which is expressed on activated T cells [17].
  • Here we identify and characterize an MCMV-encoded glycoprotein, gp34, which tightly associates with properly conformed MHC class I molecules in the ER [11].
  • In addition, we found that K(b) retained by the MCMV immune evasion gene m152 formed a novel type of complex with Endo H-sensitive m4/gp34; these complexes are distinguished from the exported complexes by being stable in 1% digitonin and unstable in 1% Nonidet P-40 [18].
  • Furthermore, glucocorticoids, which potently suppress T effector function, did not influence the expression of OX40L and CD30L in the presence of IL-7 [19].
  • The cell surface expression of CD24, CD40, CD54, CD80, CD86, OX40L and MHC class II molecules was barely altered following infection with unopsonized promastigotes or amastigotes from nude mice or with C3-coated promastigotes [20].

Regulatory relationships of Tnfsf4

  • However, OX40L can also stimulate CD8 T cells and 4-1BBL can influence CD4 T cells, raising the possibility of redundancy between the two TNFR family costimulators [21].
  • Costimulation via OX40L expressed by B cells is sufficient to determine the extent of primary CD4 cell expansion and Th2 cytokine secretion in vivo [22].
  • Effector cells taken 5 days after naive T cell activation reexpressed Ox-40 within 4 h and responded strongly to APCs expressing Ox-40L, whereas B7-1 had little effect [23].
  • OX40 ligand expression was also down-regulated on rapidly proliferating Th1 effectors [24].
  • Elevations in IL-4 production and total and Ag-specific serum IgE levels were partially inhibited during both the primary and memory immune responses to H. polygyrus in OX40L(-/-) mice [25].

Other interactions of Tnfsf4


Analytical, diagnostic and therapeutic context of Tnfsf4


  1. Critical contribution of OX40 ligand to T helper cell type 2 differentiation in experimental leishmaniasis. Akiba, H., Miyahira, Y., Atsuta, M., Takeda, K., Nohara, C., Futagawa, T., Matsuda, H., Aoki, T., Yagita, H., Okumura, K. J. Exp. Med. (2000) [Pubmed]
  2. OX40 ligation on activated T cells enhances the control of Cryptococcus neoformans and reduces pulmonary eosinophilia. Humphreys, I.R., Edwards, L., Walzl, G., Rae, A.J., Dougan, G., Hill, S., Hussell, T. J. Immunol. (2003) [Pubmed]
  3. Paradoxical dampening of anti-islet self-reactivity but promotion of diabetes by OX40 ligand. Martin-Orozco, N., Chen, Z., Poirot, L., Hyatt, E., Chen, A., Kanagawa, O., Sharpe, A., Mathis, D., Benoist, C. J. Immunol. (2003) [Pubmed]
  4. Expression of tumour necrosis factor (TNF) ligand superfamily co-stimulatory molecules CD30L, CD27L, OX40L, and 4-1BBL in murine hearts with acute myocarditis caused by Coxsackievirus B3. Seko, Y., Takahashi, N., Oshima, H., Shimozato, O., Akiba, H., Takeda, K., Kobata, T., Yagita, H., Okumura, K., Azuma, M., Nagai, R. J. Pathol. (2001) [Pubmed]
  5. Consequences of OX40-OX40 ligand interactions in langerhans cell function: enhanced contact hypersensitivity responses in OX40L-transgenic mice. Sato, T., Ishii, N., Murata, K., Kikuchi, K., Nakagawa, S., Ndhlovu, L.C., Sugamura, K. Eur. J. Immunol. (2002) [Pubmed]
  6. Positional identification of TNFSF4, encoding OX40 ligand, as a gene that influences atherosclerosis susceptibility. Wang, X., Ria, M., Kelmenson, P.M., Eriksson, P., Higgins, D.C., Samnegård, A., Petros, C., Rollins, J., Bennet, A.M., Wiman, B., de Faire, U., Wennberg, C., Olsson, P.G., Ishii, N., Sugamura, K., Hamsten, A., Forsman-Semb, K., Lagercrantz, J., Paigen, B. Nat. Genet. (2005) [Pubmed]
  7. CD4(+)CD3(-) accessory cells costimulate primed CD4 T cells through OX40 and CD30 at sites where T cells collaborate with B cells. Kim, M.Y., Gaspal, F.M., Wiggett, H.E., McConnell, F.M., Gulbranson-Judge, A., Raykundalia, C., Walker, L.S., Goodall, M.D., Lane, P.J. Immunity (2003) [Pubmed]
  8. Ox40-ligand has a critical costimulatory role in dendritic cell:T cell interactions. Chen, A.I., McAdam, A.J., Buhlmann, J.E., Scott, S., Lupher, M.L., Greenfield, E.A., Baum, P.R., Fanslow, W.C., Calderhead, D.M., Freeman, G.J., Sharpe, A.H. Immunity (1999) [Pubmed]
  9. Cross-linking of OX40 ligand, a member of the TNF/NGF cytokine family, induces proliferation and differentiation in murine splenic B cells. Stüber, E., Neurath, M., Calderhead, D., Fell, H.P., Strober, W. Immunity (1995) [Pubmed]
  10. OX40/OX40L interaction induces the expression of CXCR5 and contributes to chronic colitis induced by dextran sulfate sodium in mice. Obermeier, F., Schwarz, H., Dunger, N., Strauch, U.G., Grunwald, N., Schölmerich, J., Falk, W. Eur. J. Immunol. (2003) [Pubmed]
  11. A mouse cytomegalovirus glycoprotein, gp34, forms a complex with folded class I MHC molecules in the ER which is not retained but is transported to the cell surface. Kleijnen, M.F., Huppa, J.B., Lucin, P., Mukherjee, S., Farrell, H., Campbell, A.E., Koszinowski, U.H., Hill, A.B., Ploegh, H.L. EMBO J. (1997) [Pubmed]
  12. Ath-1, a gene determining atherosclerosis susceptibility and high density lipoprotein levels in mice. Paigen, B., Mitchell, D., Reue, K., Morrow, A., Lusis, A.J., LeBoeuf, R.C. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  13. Affinity and kinetics of the interaction between soluble trimeric OX40 ligand, a member of the tumor necrosis factor superfamily, and its receptor OX40 on activated T cells. Al-Shamkhani, A., Mallett, S., Brown, M.H., James, W., Barclay, A.N. J. Biol. Chem. (1997) [Pubmed]
  14. Constitutive OX40/OX40 ligand interaction induces autoimmune-like diseases. Murata, K., Nose, M., Ndhlovu, L.C., Sato, T., Sugamura, K., Ishii, N. J. Immunol. (2002) [Pubmed]
  15. Distinct roles for the OX40-OX40 ligand interaction in regulatory and nonregulatory T cells. Takeda, I., Ine, S., Killeen, N., Ndhlovu, L.C., Murata, K., Satomi, S., Sugamura, K., Ishii, N. J. Immunol. (2004) [Pubmed]
  16. Impairment of antigen-presenting cell function in mice lacking expression of OX40 ligand. Murata, K., Ishii, N., Takano, H., Miura, S., Ndhlovu, L.C., Nose, M., Noda, T., Sugamura, K. J. Exp. Med. (2000) [Pubmed]
  17. The T cell-B cell interaction via OX40-OX40L is necessary for the T cell-dependent humoral immune response. Stüber, E., Strober, W. J. Exp. Med. (1996) [Pubmed]
  18. The murine cytomegalovirus immune evasion protein m4/gp34 forms biochemically distinct complexes with class I MHC at the cell surface and in a pre-Golgi compartment. Kavanagh, D.G., Koszinowski, U.H., Hill, A.B. J. Immunol. (2001) [Pubmed]
  19. 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. Kim, M.Y., Anderson, G., White, A., Jenkinson, E., Arlt, W., Martensson, I.L., Erlandsson, L., Lane, P.J. J. Immunol. (2005) [Pubmed]
  20. Dendritic cells as host cells for the promastigote and amastigote stages of Leishmania amazonensis: the role of opsonins in parasite uptake and dendritic cell maturation. Prina, E., Abdi, S.Z., Lebastard, M., Perret, E., Winter, N., Antoine, J.C. J. Cell. Sci. (2004) [Pubmed]
  21. 4-1BB and OX40 act independently to facilitate robust CD8 and CD4 recall responses. Dawicki, W., Bertram, E.M., Sharpe, A.H., Watts, T.H. J. Immunol. (2004) [Pubmed]
  22. Costimulation via OX40L expressed by B cells is sufficient to determine the extent of primary CD4 cell expansion and Th2 cytokine secretion in vivo. Linton, P.J., Bautista, B., Biederman, E., Bradley, E.S., Harbertson, J., Kondrack, R.M., Padrick, R.C., Bradley, L.M. J. Exp. Med. (2003) [Pubmed]
  23. Ox-40 ligand: a potent costimulatory molecule for sustaining primary CD4 T cell responses. Gramaglia, I., Weinberg, A.D., Lemon, M., Croft, M. J. Immunol. (1998) [Pubmed]
  24. OX40 signals during priming on dendritic cells inhibit CD4 T cell proliferation: IL-4 switches off OX40 signals enabling rapid proliferation of Th2 effectors. Kim, M.Y., Bekiaris, V., McConnell, F.M., Gaspal, F.M., Raykundalia, C., Lane, P.J. J. Immunol. (2005) [Pubmed]
  25. The role of OX40 ligand interactions in the development of the Th2 response to the gastrointestinal nematode parasite Heligmosomoides polygyrus. Ekkens, M.J., Liu, Z., Liu, Q., Whitmire, J., Xiao, S., Foster, A., Pesce, J., VanNoy, J., Sharpe, A.H., Urban, J.F., Gause, W.C. J. Immunol. (2003) [Pubmed]
  26. During viral infection of the respiratory tract, CD27, 4-1BB, and OX40 collectively determine formation of CD8+ memory T cells and their capacity for secondary expansion. Hendriks, J., Xiao, Y., Rossen, J.W., van der Sluijs, K.F., Sugamura, K., Ishii, N., Borst, J. J. Immunol. (2005) [Pubmed]
  27. Peroxiredoxin 6 deficiency and atherosclerosis susceptibility in mice: significance of genetic background for assessing atherosclerosis. Wang, X., Phelan, S.A., Petros, C., Taylor, E.F., Ledinski, G., Jürgens, G., Forsman-Semb, K., Paigen, B. Atherosclerosis (2004) [Pubmed]
  28. Confirmation and high resolution mapping of an atherosclerosis susceptibility gene in mice on Chromosome 1. Phelan, S.A., Beier, D.R., Higgins, D.C., Paigen, B. Mamm. Genome (2002) [Pubmed]
  29. Therapeutic effect of anti-OX40L and anti-TNF-alpha MAbs in a murine model of chronic colitis. Totsuka, T., Kanai, T., Uraushihara, K., Iiyama, R., Yamazaki, M., Akiba, H., Yagita, H., Okumura, K., Watanabe, M. Am. J. Physiol. Gastrointest. Liver Physiol. (2003) [Pubmed]
  30. Adenovirus vector-mediated in vivo gene transfer of OX40 ligand to tumor cells enhances antitumor immunity of tumor-bearing hosts. Andarini, S., Kikuchi, T., Nukiwa, M., Pradono, P., Suzuki, T., Ohkouchi, S., Inoue, A., Maemondo, M., Ishii, N., Saijo, Y., Sugamura, K., Nukiwa, T. Cancer Res. (2004) [Pubmed]
  31. OX40 ligand-transduced tumor cell vaccine synergizes with GM-CSF and requires CD40-Apc signaling to boost the host T cell antitumor response. Gri, G., Gallo, E., Di Carlo, E., Musiani, P., Colombo, M.P. J. Immunol. (2003) [Pubmed]
WikiGenes - Universities