OX40 ligand

OX40L is the ligand for OX40 (also known as CD134 or TNFRSF4) and is stably expressed on many antigen-presenting cells such as DC2s (a subtype of dendritic cells),[1] macrophages,[2] and activated B lymphocytes.[3]

tumor necrosis factor (ligand) superfamily, member 4 (tax-transcriptionally activated glycoprotein 1, 34kDa)
Identifiers
SymbolTNFSF4
Alt. symbolsTXGP1, OX-40L, gp34, CD252
NCBI gene7292
HGNC11934
OMIM603594
RefSeqNM_003326
UniProtP23510
Other data
LocusChr. 1 q25

The OX40 molecule, on the other hand, is present on the surface of activated T lymphocytes (mainly CD4+ T cells),[4] but also on NK cells,[5] NKT cells,[6] and neutrophils.[6] The ligation of OX40-OX40L is a source of survival signal for T cells[6] and enables the development of memory T cells.[7] Signalization through these two molecules also leads to polarization towards Th2 immune response even in the environment with low levels of IL-4 cytokine.[1][8]

OX40L is also present on the surface of many non-immune cells, for example on the endothelial cells[9] and the smooth muscle cells.[10]

The surface expression of OX40L is induced by many pro-inflammatory mediators, such as TNF-α, e.g. produced by mast cells,[11] IFN-γ[12] and PGE2 (Prostaglandin E2).[13]

OX40L has also been designated CD252 (cluster of differentiation 252).[14]

Various single-nucleotide polymorphisms (SNPs) of the OX40L gene have been identified. For some of them association with systemic lupus erythematosus has been reported:[15] No association with occurrence of atherosclerosis has been found.[16]

References
  1. Maizels RM, Yazdanbakhsh M (September 2003). "Immune regulation by helminth parasites: cellular and molecular mechanisms" (PDF). Nature Reviews. Immunology. 3 (9): 733–44. doi:10.1038/nri1183. hdl:1842/465. PMID 12949497. S2CID 9323279.
  2. Lei W, Zeng DX, Zhu CH, Liu GQ, Zhang XQ, Wang CG, et al. (July 2014). "The upregulated expression of OX40/OX40L and their promotion of T cells proliferation in the murine model of asthma". Journal of Thoracic Disease. 6 (7): 979–87. doi:10.3978/j.issn.2072-1439.2014.06.34. PMC 4120161. PMID 25093096.
  3. Stüber E, Neurath M, Calderhead D, Fell HP, Strober W (May 1995). "Cross-linking of OX40 ligand, a member of the TNF/NGF cytokine family, induces proliferation and differentiation in murine splenic B cells". Immunity. 2 (5): 507–21. doi:10.1016/1074-7613(95)90031-4. PMID 7749983.
  4. Taraban VY, Rowley TF, O'Brien L, Chan HT, Haswell LE, Green MH, et al. (December 2002). "Expression and costimulatory effects of the TNF receptor superfamily members CD134 (OX40) and CD137 (4-1BB), and their role in the generation of anti-tumor immune responses". European Journal of Immunology. 32 (12): 3617–27. doi:10.1002/1521-4141(200212)32:12<3617::AID-IMMU3617>3.0.CO;2-M. PMID 12516549.
  5. Turaj AH, Cox KL, Penfold CA, French RR, Mockridge CI, Willoughby JE, et al. (February 2018). "Augmentation of CD134 (OX40)-dependent NK anti-tumour activity is dependent on antibody cross-linking". Scientific Reports. 8 (1): 2278. Bibcode:2018NatSR...8.2278T. doi:10.1038/s41598-018-20656-y. PMC 5797108. PMID 29396470.
  6. Croft M (March 2010). "Control of immunity by the TNFR-related molecule OX40 (CD134)". Annual Review of Immunology. 28 (1): 57–78. doi:10.1146/annurev-immunol-030409-101243. PMC 2882161. PMID 20307208.
  7. Frentsch M, Stark R, Matzmohr N, Meier S, Durlanik S, Schulz AR, et al. (July 2013). "CD40L expression permits CD8+ T cells to execute immunologic helper functions". Blood. 122 (3): 405–12. doi:10.1182/blood-2013-02-483586. PMC 4548794. PMID 23719298.
  8. Alt FW, Austen KF (2009). Advances in immunology. 101. Amsterdam: Academic Press. ISBN 978-0080888330. OCLC 647803349.
  9. Imura A, Hori T, Imada K, Ishikawa T, Tanaka Y, Maeda M, et al. (May 1996). "The human OX40/gp34 system directly mediates adhesion of activated T cells to vascular endothelial cells". The Journal of Experimental Medicine. 183 (5): 2185–95. doi:10.1084/jem.183.5.2185. PMC 2192546. PMID 8642328.
  10. Burgess JK, Carlin S, Pack RA, Arndt GM, Au WW, Johnson PR, et al. (April 2004). "Detection and characterization of OX40 ligand expression in human airway smooth muscle cells: a possible role in asthma?". The Journal of Allergy and Clinical Immunology. 113 (4): 683–9. doi:10.1016/j.jaci.2003.12.311. PMID 15100674.
  11. Nakae S, Suto H, Iikura M, Kakurai M, Sedgwick JD, Tsai M, Galli SJ (February 2006). "Mast cells enhance T cell activation: importance of mast cell costimulatory molecules and secreted TNF". Journal of Immunology. 176 (4): 2238–48. doi:10.4049/jimmunol.176.4.2238. PMID 16455980. S2CID 22718354.
  12. Wang Y, Li M, Song M, Xu X, Xiong J, Yang X, et al. (February 2008). "Expression of OX40 ligand in microglia activated by IFN-gamma sustains a protective CD4+ T-cell response in vitro". Cellular Immunology. 251 (2): 86–92. doi:10.1016/j.cellimm.2008.04.002. PMID 18485335.
  13. Krause P, Bruckner M, Uermösi C, Singer E, Groettrup M, Legler DF (March 2009). "Prostaglandin E(2) enhances T-cell proliferation by inducing the costimulatory molecules OX40L, CD70, and 4-1BBL on dendritic cells". Blood. 113 (11): 2451–60. doi:10.1182/blood-2008-05-157123. PMID 19029446.
  14. Universal protein resource accession number P23510 for "TNFSF4 - Tumor necrosis factor ligand superfamily member 4 - Homo sapiens (Human) " at UniProt.
  15. Lu MM, Xu WD, Yang J, Ye QL, Feng CC, Li J, et al. (July 2013). "Association of TNFSF4 polymorphisms with systemic lupus erythematosus: a meta-analysis". Modern Rheumatology. 23 (4): 686–93. doi:10.3109/s10165-012-0708-8. PMID 22850862. S2CID 218988187.
  16. Huang Q, Yang QD, Tan XL, Feng J, Tang T, Xia J, et al. (April 2014). "Absence of association between atherosclerotic cerebral infarction and TNFSF4/TNFRSF4 single nucleotide polymorphisms rs1234313, rs1234314 and rs17568 in a Chinese population". The Journal of International Medical Research. 42 (2): 436–43. doi:10.1177/0300060514521154. PMID 24595151. S2CID 35831673.
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