OX40 ligand

Summary

Gene Symbol: OX40 ligand
Description: TNF superfamily member 4
Alias: CD134L, CD252, GP34, OX-40L, OX4OL, TNLG2B, TXGP1, tumor necrosis factor ligand superfamily member 4, CD134 ligand, OX40 antigen ligand, glycoprotein Gp34, tax-transcriptionally activated glycoprotein 1 (34kD), tumor necrosis factor (ligand) superfamily member 4, tumor necrosis factor ligand 2B, tumor necrosis factor superfamily member 4
Species: human
Products:     OX40 ligand

Top Publications

  1. Gramaglia I, Weinberg A, Lemon M, Croft M. Ox-40 ligand: a potent costimulatory molecule for sustaining primary CD4 T cell responses. J Immunol. 1998;161:6510-7 pubmed
    ..These data suggest that Ox-40/Ox-40L interactions act after initial activation events to prolong clonal expansion and enhance effector cytokine secretion, and may be involved in promoting long-lived primary CD4 responses. ..
  2. Imura A, Hori T, Imada K, Ishikawa T, Tanaka Y, Maeda M, et al. The human OX40/gp34 system directly mediates adhesion of activated T cells to vascular endothelial cells. J Exp Med. 1996;183:2185-95 pubmed
    ..We then found that gp34, the ligand of OX40, was expressed on HUVECs and other types of vascular endothelial cells...
  3. Burgess J, Carlin S, Pack R, Arndt G, Au W, Johnson P, et al. Detection and characterization of OX40 ligand expression in human airway smooth muscle cells: a possible role in asthma?. J Allergy Clin Immunol. 2004;113:683-9 pubmed
    ..The purpose of this study was to determine whether OX40 ligand (OX40L), a molecule known to be involved in T-cell activation, was present on the ASM cell surface...
  4. Liu Y. Thymic stromal lymphopoietin and OX40 ligand pathway in the initiation of dendritic cell-mediated allergic inflammation. J Allergy Clin Immunol. 2007;120:238-44; quiz 245-6 pubmed
    ..In addition, OX40 ligand was found to be the TSLP-induced molecule on dendritic cells that triggers inflammatory T(H)2 differentiation ..
  5. Olofsson P, Söderström L, Jern C, Sirsjo A, Ria M, Sundler E, et al. Genetic variants of TNFSF4 and risk for carotid artery disease and stroke. J Mol Med (Berl). 2009;87:337-46 pubmed publisher
    ..This study shows that TNFSF4 is expressed on antigen-presenting cells in human carotid atherosclerotic lesions but provides no evidence for an association of TNFSF4 gene variation with the risk for ischemic stroke. ..
  6. Godfrey W, Fagnoni F, Harara M, Buck D, Engleman E. Identification of a human OX-40 ligand, a costimulator of CD4+ T cells with homology to tumor necrosis factor. J Exp Med. 1994;180:757-62 pubmed
    ..The encoded protein is identified as gp34, a type II transmembrane antigen previously known to be expressed only by human T cell lymphotropic virus 1-..
  7. Ohshima Y, Tanaka Y, Tozawa H, Takahashi Y, Maliszewski C, Delespesse G. Expression and function of OX40 ligand on human dendritic cells. J Immunol. 1997;159:3838-48 pubmed
    b>OX40 ligand (OX40L), a member of the TNF family, was shown to be capable of signaling both the cells on which it is expressed and those expressing OX40, its cognate receptor...
  8. Hikami K, Tsuchiya N, Tokunaga K. New variations in human OX40 ligand (CD134L) gene. Genes Immun. 2000;1:521-2 pubmed
    We found three new variations in the OX40 ligand (OX40L, CD134L) gene and its 5' upstream region. -921 (G-->A) at 5' upstream region, -19 (C-->G) at 5' untranslated region, and 202 + 25 (G-->T) at intron 2 were identified...
  9. Kashiwakura J, Yokoi H, Saito H, Okayama Y. T cell proliferation by direct cross-talk between OX40 ligand on human mast cells and OX40 on human T cells: comparison of gene expression profiles between human tonsillar and lung-cultured mast cells. J Immunol. 2004;173:5247-57 pubmed
    ..higher expression levels for CC chemokines (CCL3 and 4), which recruit T cells, and for TNFR superfamilies (OX40 ligand and 4-1BB ligand), which induce proliferation of T cells...

More Information

Publications102 found, 100 shown here

  1. Ito T, Wang Y, Duramad O, Hanabuchi S, Perng O, Gilliet M, et al. OX40 ligand shuts down IL-10-producing regulatory T cells. Proc Natl Acad Sci U S A. 2006;103:13138-43 pubmed
    ..We report that OX40 ligand (OX40L) completely inhibited the generation of IL-10-producing Tr1 cells from naïve and memory CD4(+) T cells ..
  2. Cunninghame Graham D, Graham R, Manku H, Wong A, Whittaker J, Gaffney P, et al. Polymorphism at the TNF superfamily gene TNFSF4 confers susceptibility to systemic lupus erythematosus. Nat Genet. 2008;40:83-9 pubmed
    ..We hypothesize that increased expression of TNFSF4 predisposes to SLE either by quantitatively augmenting T cell-APC interaction or by influencing the functional consequences of T cell activation via TNFRSF4. ..
  3. Seshasayee D, Lee W, Zhou M, Shu J, Suto E, Zhang J, et al. In vivo blockade of OX40 ligand inhibits thymic stromal lymphopoietin driven atopic inflammation. J Clin Invest. 2007;117:3868-78 pubmed
    ..In our current study, we have shown that OX40 ligand (OX40L) is a critical in vivo mediator of TSLP-mediated Th2 responses...
  4. Li J, Li L, Shang X, Benson J, Merle Elloso M, Schantz A, et al. Negative regulation of IL-17 production by OX40/OX40L interaction. Cell Immunol. 2008;253:31-7 pubmed publisher
    ..b>OX40 ligand (OX40L) is an early-stage activator of T-cells through its interaction with CD134 (OX40) that is up-regulated ..
  5. Delgado Vega A, Abelson A, Sanchez E, Witte T, D Alfonso S, Galeazzi M, et al. Replication of the TNFSF4 (OX40L) promoter region association with systemic lupus erythematosus. Genes Immun. 2009;10:248-53 pubmed publisher
    The tumor necrosis factor ligand superfamily member 4 gene (TNFSF4) encodes the OX40 ligand (OX40L), a costimulatory molecule involved in T-cell activation...
  6. Gourh P, Arnett F, Tan F, Assassi S, Divecha D, Paz G, et al. Association of TNFSF4 (OX40L) polymorphisms with susceptibility to systemic sclerosis. Ann Rheum Dis. 2010;69:550-5 pubmed publisher
    ..factor ligand superfamily member 4 gene (TNFSF4, OX40L), which encodes for the T cell costimulatory molecule OX40 ligand, has been identified as a susceptibility gene for the development of systemic lupus erythematosus (SLE)...
  7. Han J, Zheng H, Cui Y, Sun L, Ye D, Hu Z, et al. Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus. Nat Genet. 2009;41:1234-7 pubmed publisher
    ..This study not only advances our understanding of the genetic basis of SLE but also highlights the value of performing GWAS in diverse ancestral populations. ..
  8. Ria M, Lagercrantz J, Samnegard A, Boquist S, Hamsten A, Eriksson P. A common polymorphism in the promoter region of the TNFSF4 gene is associated with lower allele-specific expression and risk of myocardial infarction. PLoS ONE. 2011;6:e17652 pubmed publisher
    ..Our data indicate that the TNFSF4 rs45454293T-allele is associated with lower TNFSF4 expression and increased risk of MI. ..
  9. Baum P, Gayle R, Ramsdell F, Srinivasan S, Sorensen R, Watson M, et al. Molecular characterization of murine and human OX40/OX40 ligand systems: identification of a human OX40 ligand as the HTLV-1-regulated protein gp34. EMBO J. 1994;13:3992-4001 pubmed
    ..The ligand (muOX40L) is a type II membrane protein with significant identity to human gp34 (gp34), a protein whose expression on HTLV-1-infected human leukemic T cells is regulated by the tax gene...
  10. Ito T, Amakawa R, Inaba M, Hori T, Ota M, Nakamura K, et al. Plasmacytoid dendritic cells regulate Th cell responses through OX40 ligand and type I IFNs. J Immunol. 2004;172:4253-9 pubmed
    ..of PDCs after short (24-h) or long (72-h) culture with stimuli and have assessed the expression and function of OX40 ligand (OX40L) in PDC-mediated Th polarization in addition to type I IFN-dependent responses...
  11. Wang X, Ria M, Kelmenson P, Eriksson P, Higgins D, Samnegard A, et al. Positional identification of TNFSF4, encoding OX40 ligand, as a gene that influences atherosclerosis susceptibility. Nat Genet. 2005;37:365-72 pubmed
    ..trait locus region encompasses 11 known genes, including Tnfsf4 (also called Ox40l or Cd134l), which encodes OX40 ligand. Here we report that mice with targeted mutations of Tnfsf4 had significantly (P <or= 0...
  12. Malarstig A, Eriksson P, Rose L, Diehl K, Hamsten A, Ridker P, et al. Genetic variants of tumor necrosis factor superfamily, member 4 (TNFSF4), and risk of incident atherothrombosis and venous thromboembolism. Clin Chem. 2008;54:833-40 pubmed publisher
    ..Our present findings, if corroborated in other prospective investigations, suggest that the TNFSF4 variants tested may be useful indicators for assessing the risk of venous thromboembolism. ..
  13. Chang Y, Yang W, Zhao M, Mok C, Chan T, Wong R, et al. Association of BANK1 and TNFSF4 with systemic lupus erythematosus in Hong Kong Chinese. Genes Immun. 2009;10:414-20 pubmed publisher
    ..26 x 10(-3)), but not vice versa (P=0.55). These findings suggest that multiple independent genetic variants may be present within the gene locus, which exert their effects on SLE pathogenesis through different mechanisms. ..
  14. Croft M. Control of immunity by the TNFR-related molecule OX40 (CD134). Annu Rev Immunol. 2010;28:57-78 pubmed publisher
    ..the most important and prominent interactions in this family is that between OX40 (CD134) and its partner OX40L (CD252)...
  15. Nordmark G, Kristjansdottir G, Theander E, Appel S, Eriksson P, Vasaitis L, et al. Association of EBF1, FAM167A(C8orf13)-BLK and TNFSF4 gene variants with primary Sjögren's syndrome. Genes Immun. 2011;12:100-9 pubmed publisher
    ..EBF1, BLK and TNFSF4 are all involved in B-cell differentiation and activation, and we conclude that polymorphisms in several susceptibility genes in the immune system contribute to the pathogenesis of primary SS. ..
  16. Bossini Castillo L, Broen J, Simeon C, Beretta L, Vonk M, Ortego Centeno N, et al. A replication study confirms the association of TNFSF4 (OX40L) polymorphisms with systemic sclerosis in a large European cohort. Ann Rheum Dis. 2011;70:638-41 pubmed publisher
    ..03 to 1.26; OR 1.20, 95% CI 1.08 to 1.35; OR 1.23, 95% CI 1.07 to 1.42, respectively). The data confirm the influence of TNFSF4 polymorphisms in SSc genetic susceptibility, especially in subsets of patients positive for lcSSc and ACA. ..
  17. Yoshioka T, Nakajima A, Akiba H, Ishiwata T, Asano G, Yoshino S, et al. Contribution of OX40/OX40 ligand interaction to the pathogenesis of rheumatoid arthritis. Eur J Immunol. 2000;30:2815-23 pubmed
    b>OX40 ligand (OX40L) and OX40 (CD134) are a pair of cell surface molecules belonging to the TNF/TNF receptor family...
  18. Compaan D, Hymowitz S. The crystal structure of the costimulatory OX40-OX40L complex. Structure. 2006;14:1321-30 pubmed
    ..These structures demonstrate the structural plasticity of TNFSF members and their interactions with receptors. ..
  19. Yamaguchi S, Yamada Y, Metoki N, Yoshida H, Satoh K, Ichihara S, et al. Genetic risk for atherothrombotic cerebral infarction in individuals stratified by sex or conventional risk factors for atherosclerosis. Int J Mol Med. 2006;18:871-83 pubmed
    ..Stratification of subjects on the basis of sex or conventional risk factors for atherosclerosis may therefore be important in order to achieve the personalized prevention of ACI with the use of genetic information. ..
  20. Mashimo Y, Suzuki Y, Hatori K, Tabara Y, Miki T, Tokunaga K, et al. Association of TNFRSF4 gene polymorphisms with essential hypertension. J Hypertens. 2008;26:902-13 pubmed publisher
    ..The C-T-G-A haplotype showed a lower promoter activity than other haplotypes, suggesting a relationship with disease susceptibility. Our results suggest that TNFRSF4 is a female-specific susceptible gene for essential hypertension. ..
  21. Sanchez E, Webb R, Rasmussen A, Kelly J, Riba L, Kaufman K, et al. Genetically determined Amerindian ancestry correlates with increased frequency of risk alleles for systemic lupus erythematosus. Arthritis Rheum. 2010;62:3722-9 pubmed publisher
    ..0001). SLE patients with 43% more Amerindian ancestry were predicted to carry 1 additional risk allele. Our results demonstrate that Amerindian ancestry is associated with an increased number of risk alleles for SLE. ..
  22. Chen Z, Wang C, Wei F, Xu B, Liu J, Pu Y, et al. Adenovirus-mediated OX40Ig gene transfer induces long-term survival of orthotopic liver allograft in rats. Transpl Immunol. 2018;48:32-38 pubmed publisher
    ..Through OX40/OX4OL pathways, OX40Ig created an immunosuppressive effect after liver transplantation in rats...
  23. Tsai J, Wang H, Chiu C, Liao E. The effect of Dermatophagoides pteronyssinus group 7 allergen (Der p 7) on dendritic cells and its role in T cell polarization. Immunobiology. 2016;221:1319-28 pubmed publisher
    ..BMDCs could be activated by Der p 7 through TLR4 and DC-SIGN, and followed by the expression of OX40 ligand (OX40L) and Jagged-1, the expressions of IL4(+)/CD4(+) cells were enhanced...
  24. Najar M, Fayyad Kazan H, Faour W, El Taghdouini A, Raicevic G, van Grunsven L, et al. Immuno-biological comparison of hepatic stellate cells in a reverted and activated state. Biomed Pharmacother. 2018;98:52-62 pubmed publisher
    ..molecules (CD29, CD54, CD58, CD106 and CD166), human leucocyte antigen HLA-G, co-stimulatory molecules (CD40 and CD252), as well as the immunoregulatory molecules (CD200 and CD274)...
  25. Li L, Chen S, Wen X, Wang Q, Lv G, Li J, et al. Positive Association between ANKRD55 Polymorphism 7731626 and Dermatomyositis/Polymyositis with Interstitial Lung Disease in Chinese Han Population. Biomed Res Int. 2017;2017:2905987 pubmed publisher
    ..A decreased frequency of rs7731626-A in DM-ILD and DM/PM-ILD patients suggests that the A variant may be protective against DM/PM-ILD. ..
  26. Rühlemann M, Degenhardt F, Thingholm L, Wang J, Skieceviciene J, Rausch P, et al. Application of the distance-based F test in an mGWAS investigating β diversity of intestinal microbiota identifies variants in SLC9A8 (NHE8) and 3 other loci. Gut Microbes. 2018;9:68-75 pubmed publisher
    ..Our findings highlight the utility of the high-performance DBF test in β diversity GWAS and emphasize the important role of host genetics and immunity in shaping the human intestinal microbiota. ..
  27. Karulf M, Kelly A, Weinberg A, Gold J. OX40 ligand regulates inflammation and mortality in the innate immune response to sepsis. J Immunol. 2010;185:4856-62 pubmed publisher
    ..The purpose of this study was to determine the role for OX40-OX40 ligand (OX40L) interaction in the innate immune response to polymicrobial sepsis...
  28. Otani T, Tsuji Takayama K, Okochi A, Yamamoto M, Takeuchi M, Yamasaki F, et al. Stromal cells' B7-1 is a key stimulatory molecule for interleukin-10 production by HOZOT, a multifunctional regulatory T-cell line. Immunol Cell Biol. 2011;89:246-54 pubmed publisher
    ..MHC class II or other costimulatory molecules, such as ICOSL (CD275), PD-L1 (CD274), PD-L2 (CD273), CD40, OX40L (CD252) and 4-1BBL (CD137L) in the absence of stimulation...
  29. Zhao H, Xu R, Huang X, Cheng S, Huang M, Yue H, et al. Curcumin improves regulatory T cells in gut-associated lymphoid tissue of colitis mice. World J Gastroenterol. 2016;22:5374-83 pubmed publisher
    ..IL-2, IL-6, IL-12 p40, IL-17 and IL-21 and the expression of costimulatory molecules (CD205, CD54 [ICAM-1], TLR4, CD252[OX40 L], CD256 [RANK] and CD254 [RANK L]) of DCs were notably inhibited in colitis mice treated with Cur...
  30. Song R, Wang Q, Yao Q, Shao X, Li L, Wang W, et al. TNFSF4 Gene Variations Are Related to Early-Onset Autoimmune Thyroid Diseases and Hypothyroidism of Hashimoto's Thyroiditis. Int J Mol Sci. 2016;17: pubmed publisher
    The aim of the current study was to examine whether the polymorphism loci of the tumor necrosis factor superfamily member 4 (TNFSF4) gene increase the risk of susceptibility to autoimmune thyroid diseases (AITDs) in the Han Chinese ..
  31. Shah A, Haynes C, Craig D, Sebek J, Grass E, Abramson K, et al. Genetic variants associated with vein graft stenosis after coronary artery bypass grafting. Heart Surg Forum. 2015;18:E1-5 pubmed publisher
    ..These polymorphisms merit further investigation, as they could assist in stratifying patients with multi-vessel coronary artery disease, which could lead to alterations in management and revascularization strategy. ..
  32. Brzóska K, Kruszewski M. Toward the development of transcriptional biodosimetry for the identification of irradiated individuals and assessment of absorbed radiation dose. Radiat Environ Biophys. 2015;54:353-63 pubmed publisher
    ..The samples were clearly grouped according to the absorbed doses of radiation and not to the time interval after irradiation or to the blood donor. ..
  33. Lu C, Jia H, Xu A. The rs3850641 polymorphism of the TNFSF4 gene increases the risk of myocardial infarction in a Chinese Han population. Biosci Rep. 2018;38: pubmed publisher
    b>Tumor necrosis factor superfamily member 4 (TNFSF4), also known as Ox40 ligand (Ox40l), plays an important role in atherosclerosis development...
  34. Ilves T, Harvima I. OX40 ligand and OX40 are increased in atopic dermatitis lesions but do not correlate with clinical severity. J Eur Acad Dermatol Venereol. 2013;27:e197-205 pubmed publisher
    The interaction between the OX40 ligand (OX40L) and OX40 has been suggested to have pathogenetic significance in atopic dermatitis (AD)...
  35. Sanchez E, Nadig A, Richardson B, Freedman B, Kaufman K, Kelly J, et al. Phenotypic associations of genetic susceptibility loci in systemic lupus erythematosus. Ann Rheum Dis. 2011;70:1752-7 pubmed publisher
    ..The findings suggest that genetic profiling might be a useful tool to predict disease manifestations in lupus patients in the future. ..
  36. Weixler B, Cremonesi E, Sorge R, Muraro M, Delko T, Nebiker C, et al. OX40 expression enhances the prognostic significance of CD8 positive lymphocyte infiltration in colorectal cancer. Oncotarget. 2015;6:37588-99 pubmed publisher
    OX40 is a TNF receptor family member expressed by activated T cells. Its triggering by OX40 ligand promotes lymphocyte survival and memory generation...
  37. Zheng R, Chen F, Gao W, Wang D, Yang Q, Wang K, et al. The TH2-polarizing function of atopic interleukin 17 receptor B-positive dendritic cells up-regulated by lipopolysaccharide. Ann Allergy Asthma Immunol. 2017;118:474-482.e1 pubmed publisher
    ..In addition, LPS increased the expression of the OX40 ligand (OX40L) but decreased inducible costimulator ligand on atopic CD86+ mo-DCs...
  38. Kobayashi M, Takaori Kondo A, Fukunaga K, Miyoshi H, Uchiyama T. Lentiviral gp34/OX40L gene transfer into dendritic cells facilitates alloreactive CD4+ T-cell response in vitro. Int J Hematol. 2004;79:377-83 pubmed
    ..In this study, we demonstrated that lentiviral transduction of DCs with the gp34/OX40L gene, one of the costimulatory molecules, facilitates alloreactive CD4+ T-cell response in vitro...
  39. Kondo K, Okuma K, Tanaka R, Zhang L, Kodama A, Takahashi Y, et al. Requirements for the functional expression of OX40 ligand on human activated CD4+ and CD8+ T cells. Hum Immunol. 2007;68:563-71 pubmed
    ..Altogether the present study findings indicate that functional OX40L is inducible on human activated CD4+ and CD8+ T cells, and that the expression is enhanced by TGF-beta1. ..
  40. Chen Y, Zhang L, Huang H, Liu R, Li X, Qiang O, et al. Association of OX40 and OX40L gene polymorphisms with acute coronary syndrome in a Han Chinese population. DNA Cell Biol. 2011;30:597-602 pubmed publisher
    ..In conclusion, OX40 gene polymorphism may be associated with a risk of ACS in the Han Chinese population, although the association between OX40L polymorphisms and ACS requires further investigation. ..
  41. Ohtani K, Tsujimoto A, Tsukahara T, Numata N, Miura S, Sugamura K, et al. Molecular mechanisms of promoter regulation of the gp34 gene that is trans-activated by an oncoprotein Tax of human T cell leukemia virus type I. J Biol Chem. 1998;273:14119-29 pubmed
    We investigated the molecular mechanism of transcriptional activation of the gp34 gene by the Tax oncoprotein of human T cell leukemia virus type I (HTLV-I)...
  42. Motai Y, Takahashi M, Takachi T, Higuchi M, Hara T, Mizuguchi M, et al. Human T-cell leukemia virus type 1 (HTLV-1) Tax1 oncoprotein but not HTLV-2 Tax2 induces the expression of OX40 ligand by interacting with p52/p100 and RelB. Virus Genes. 2016;52:4-13 pubmed publisher
    ..We found that Tax1 but not Tax2 induces the expression of OX40 ligand (OX40L) in a human T-cell line...
  43. Huang Q, Liu X, Feng J, Wen Y, He W, Liu Y. [Association between tumor necrosis factor superfamily member 4 gene polymorphism and risk of asymptomatic carotid vulnerable plaque in a Chinese population]. Zhonghua Liu Xing Bing Xue Za Zhi. 2015;36:998-1001 pubmed
    ..b>Tumor necrosis factor superfamily member 4 (TNFSF4) plays a key role in the process of atherosclerosis, a common risk factor for both ..
  44. Rios Doria J, Harper J, Rothstein R, Wetzel L, Chesebrough J, MARRERO A, et al. Antibody-Drug Conjugates Bearing Pyrrolobenzodiazepine or Tubulysin Payloads Are Immunomodulatory and Synergize with Multiple Immunotherapies. Cancer Res. 2017;77:2686-2698 pubmed publisher
    ..Combinations of ADCs with immuno-oncology drugs, including PD-1 or PD-L1 antibodies, OX40 ligand, or GITR ligand fusion proteins, produced synergistic antitumor responses...
  45. Mehta A, Duan W, Doerner A, Traves S, Broide D, Proud D, et al. Rhinovirus infection interferes with induction of tolerance to aeroantigens through OX40 ligand, thymic stromal lymphopoietin, and IL-33. J Allergy Clin Immunol. 2016;137:278-288.e6 pubmed publisher
    ..RV1B promoted early in vivo expression of the TNF family protein OX40 ligand on lung dendritic cells that was dependent on the innate cytokine thymic stromal lymphopoietin (TSLP) and also ..
  46. González Roldán N, Orinska Z, Ewers H, Bulfone Paus S. CD252 regulates mast cell mediated, CD1d-restricted NKT-cell activation in mice. Eur J Immunol. 2016;46:432-9 pubmed publisher
    ..Moreover, the costimulatory molecules CD48, CD137L, CD252, CD274, and CD275 affected MC-induced IFN-γ release and iNKT-cell proliferation...
  47. Arch R, Thompson C. 4-1BB and Ox40 are members of a tumor necrosis factor (TNF)-nerve growth factor receptor subfamily that bind TNF receptor-associated factors and activate nuclear factor kappaB. Mol Cell Biol. 1998;18:558-65 pubmed
    ..Taken together, our results indicate that 4-1BB and Ox40 bind TRAF proteins to initiate a signaling cascade leading to activation of nuclear factor kappaB. ..
  48. Webb R, Kelly J, Somers E, Hughes T, Kaufman K, Sanchez E, et al. Early disease onset is predicted by a higher genetic risk for lupus and is associated with a more severe phenotype in lupus patients. Ann Rheum Dis. 2011;70:151-6 pubmed publisher
    ..A more severe SLE phenotype is found in patients with early-onset disease in a large multi-racial cohort, independent of gender, race and disease duration. ..
  49. Feng J, Liu Y, Yang Q, Zhu Z, Xia K, Tan X, et al. TNFSF4 gene polymorphism rs3861950 but not rs3850641 is associated with the risk of cerebral infarction in a Chinese population. J Thromb Thrombolysis. 2013;36:307-13 pubmed publisher
    b>Tumor necrosis factor superfamily member 4 (TNFSF4) plays a key role in the process of atherosclerosis, a common risk factor for both myocardial and cerebral infarctions...
  50. Sun F, Li P, Chen H, Wu Z, Xu J, Shen M, et al. Association studies of TNFSF4, TNFAIP3 and FAM167A-BLK polymorphisms with primary Sjogren's syndrome in Han Chinese. J Hum Genet. 2013;58:475-9 pubmed publisher
    ..The differential genetic risk profiles from other autoimmune diseases may indicate differential molecular mechanisms underlying pSS pathogenesis in this group. ..
  51. Zhou X, Cheng F, Qi Y, Zhao M, Zhang H. A replication study from Chinese supports association between lupus-risk allele in TNFSF4 and renal disorder. Biomed Res Int. 2013;2013:597921 pubmed publisher
    ..The detailed mechanisms of its role in pathogenesis will still be further needed. ..
  52. Lu J, Wang H, Yuan F, Wu L, Wang B, Ye D. Lack of association of tumor necrosis factor superfamily member 4 (TNFSF4) gene polymorphisms (rs3850641 and rs17568) with coronary heart disease and stroke: A systematic review and meta-analysis. Anatol J Cardiol. 2018;19:86-93 pubmed publisher
    To evaluate the association between the tumor necrosis factor superfamily member 4 (TNFSF4) gene polymorphisms and common cardiovascular and cerebrovascular diseases...
  53. Siddiqui S, Mistry V, Doe C, Stinson S, Foster M, Brightling C. Airway wall expression of OX40/OX40L and interleukin-4 in asthma. Chest. 2010;137:797-804 pubmed publisher
    ..Whether these costimulatory molecules have a role as targets for asthma requires further investigation. ..
  54. Lee Y, Song G. Associations between TNFSF4 and TRAF1-C5 gene polymorphisms and systemic lupus erythematosus: a meta-analysis. Hum Immunol. 2012;73:1050-4 pubmed publisher
    ..This meta-analysis confirms that TNFSF4 polymorphisms are associated with susceptibility to SLE in Asians and Europeans. An association was found between the rs10818488 polymorphism of TRAF1-C5 and susceptibility to SLE in Europeans. ..
  55. Lu W, Albalawi F, Beckel J, Lim J, Laties A, Mitchell C. The P2X7 receptor links mechanical strain to cytokine IL-6 up-regulation and release in neurons and astrocytes. J Neurochem. 2017;141:436-448 pubmed publisher
    ..The mechanosensitive up-regulation and release of cytokine IL-6 from the retina involves the P2X7 receptor, with both astrocytes and neurons contributing to the response. ..
  56. Godefroy E, Manches O, Dreno B, Hochman T, Rolnitzky L, Labarriere N, et al. Matrix metalloproteinase-2 conditions human dendritic cells to prime inflammatory T(H)2 cells via an IL-12- and OX40L-dependent pathway. Cancer Cell. 2011;19:333-46 pubmed publisher
    ..Active MMP-2, therefore, acts as an endogenous type 2 "conditioner" and may play a role in the observed prevalence of detrimental type 2 responses in melanoma. ..
  57. Papadopoulos C, Terzis G, Papadimas G, Manta P. OX40-OX40L expression in idiopathic inflammatory myopathies. Anal Quant Cytopathol Histpathol. 2013;35:17-26 pubmed
    ..Expression of OX40L by different types of cells within the inflamed muscle implies that OX40-OX40L interaction may contribute in disease mechanisms through different pathways. ..
  58. Turaj A, Cox K, Penfold C, French R, Mockridge C, Willoughby J, et al. Augmentation of CD134 (OX40)-dependent NK anti-tumour activity is dependent on antibody cross-linking. Sci Rep. 2018;8:2278 pubmed publisher
    ..Stimulation with an agonistic anti-CD134 mAb but not CD134 ligand, increased IFNγ production and cytotoxicity of human NK cells, but this was dependent on simultaneous antibody:..
  59. Manku H, Graham D, Vyse T. Association of the co-stimulator OX40L with systemic lupus erythematosus. J Mol Med (Berl). 2009;87:229-34 pubmed publisher
    ..Like OX40L, several genes recently identified in WGA studies are components of B cell pathways. Collectively, these genes will help us to unravel the mechanisms by which aberrant B cell signalling results in lupus pathogenesis. ..
  60. Kurche J, Haluszczak C, McWilliams J, Sanchez P, Kedl R. Type I IFN-dependent T cell activation is mediated by IFN-dependent dendritic cell OX40 ligand expression and is independent of T cell IFNR expression. J Immunol. 2012;188:585-93 pubmed publisher
    ..Further, we find that dendritic cell (DC) expression of the TNF superfamily member OX40 ligand was dependent on type I IFN signaling in the DC, resulting in a reduced CD4(+) T cell response that could be ..
  61. Sgourakis N, Natarajan K, Ying J, Vögeli B, Boyd L, Margulies D, et al. The structure of mouse cytomegalovirus m04 protein obtained from sparse NMR data reveals a conserved fold of the m02-m06 viral immune modulator family. Structure. 2014;22:1263-1273 pubmed publisher
    ..using sparse nuclear magnetic resonance data and integrative Rosetta modeling to determine the structure of the m04/gp34 immunoevasin extracellular domain...
  62. Maalhagh M, Shojaei M, Erfanian S, Sotoodeh Jahromi A, Sanie M, Yusefi A, et al. Lack of Association Between rs17568 Polymorphism in OX40 Gene and Myocardial Infarction, Southern of Iran. Glob J Health Sci. 2015;8:41-6 pubmed publisher
    ..OX40 is a member of the TNF super family receptor protein. OX40 and OX40 ligand are co-stimulators for T-cells and can increase inflammatory response in atherosclerotic plaques...
  63. Kondo K, Okuma K, Tanaka R, Matsuzaki G, Ansari A, Tanaka Y. Rapid induction of OX40 ligand on primary T cells activated under DNA-damaging conditions. Hum Immunol. 2008;69:533-42 pubmed publisher
    ..freshly activated in vitro in the presence of TGF-beta express the cell surface T-cell costimulating molecule OX40 ligand (OX40L)...
  64. Wang Q, Chen Y, Xie F, Ge Y, Wang X, Zhang X. A novel agonist anti-human OX40L monoclonal antibody that stimulates T cell proliferation and enhances cytokine secretion. Hybridoma (Larchmt). 2009;28:269-76 pubmed publisher
    OX40L (CD252), a membrane-bound member of the tumor necrosis factor superfamily, is known to be a critical co-stimulatory molecule during immune response...
  65. Manku H, Langefeld C, Guerra S, Malik T, ALARCON RIQUELME M, Anaya J, et al. Trans-ancestral studies fine map the SLE-susceptibility locus TNFSF4. PLoS Genet. 2013;9:e1003554 pubmed publisher
    ..Our data confirm a global signal at TNFSF4 and a role for the expressed product at multiple stages of lymphocyte dysregulation during SLE pathogenesis. We confirm the validity of trans-ancestral mapping in a complex trait. ..
  66. Wang Y, Li G, Fu Y, Wang H, Shen Z. Blockade of OX40/OX40 ligand to decrease cytokine messenger RNA expression in acute renal allograft rejection in vitro. Transplant Proc. 2013;45:2565-8 pubmed publisher
    ..05, and P < .01, respectively). Blocking of the interaction between OX40 and OX40L in vitro inhibited production of Thl and Th2 type cytokines. ..
  67. Cheng J, Cen J, Cai M, Xu S, Li L, Li Z, et al. Association between TNFSF4 tagSNPs and myocardial infarction in a Chinese Han population. Genet Mol Res. 2015;14:6136-45 pubmed publisher
    b>Tumor necrosis factor superfamily member 4 (TNFSF4) plays an important role in atherosclerosis development. However, the biological significance of TNFSF4 variants on myocardial infarction (MI) pathogenesis remains poorly understood...
  68. Miura S, Ohtani K, Numata N, Niki M, Ohbo K, Ina Y, et al. Molecular cloning and characterization of a novel glycoprotein, gp34, that is specifically induced by the human T-cell leukemia virus type I transactivator p40tax. Mol Cell Biol. 1991;11:1313-25 pubmed
    We have cloned and sequenced a cDNA encoding gp34, a novel glycoprotein expressed in cells bearing human T-cell leukemia virus type I (HTLV-I)...
  69. Muller N, Wyzgol A, Munkel S, Pfizenmaier K, Wajant H. Activity of soluble OX40 ligand is enhanced by oligomerization and cell surface immobilization. FEBS J. 2008;275:2296-304 pubmed publisher
    b>OX40 ligand (OX40L) and OX40 are typical members of the tumor necrosis factor ligand family and the tumor necrosis factor receptor superfamily, respectively, and are involved in the costimulation and differentiation of T cells...
  70. Qin W, Hongya W, Yongjing C, Fang X, Yue M, Xuekun Z, et al. Increased OX40 and soluble OX40 ligands in children with Henoch-Schonlein purpura: association with renal involvement. Pediatr Allergy Immunol. 2011;22:54-9 pubmed publisher
    ..However, the regulation of the T cells in HSP remains poorly understood. In this study, OX40/OX40L (CD134/CD252) costimulatory pathway, which could promote T-cell activation and long survival, was investigated...
  71. Ezzat M, Imam S, Shaheen K, Elbrhami E. Serum OX40 ligand levels in asthmatic children: a potential biomarker of severity and persistence. Allergy Asthma Proc. 2011;32:313-8 pubmed publisher
    ..OX40L may represent a useful biomarker of monitoring allergic inflammation. OX40L is one of the most promising targets of immune intervention for treatment of these diseases. ..
  72. Liu R, Qiao Y, Liu Y, Li X, Chen Y, Qiang O, et al. Genetic variation in the OX40L/OX40 system and plasma lipid and lipoprotein levels in a Chinese hypertriglyceridemic population. Genet Test Mol Biomarkers. 2013;17:207-13 pubmed publisher
  73. Garner C, Ahn R, Ding Y, Steele L, Stoven S, Green P, et al. Genome-wide association study of celiac disease in North America confirms FRMD4B as new celiac locus. PLoS ONE. 2014;9:e101428 pubmed publisher
    ..Preliminary, suggestive statistical evidence for association with the two traits was found at chromosomes 3p21.31, 6q15, 6q25, 1q24.3 and 10p11.23, with future studies being required to validate the reported associations. ..
  74. Xu S, Yin M, Koroleva M, Mastrangelo M, Zhang W, Bai P, et al. SIRT6 protects against endothelial dysfunction and atherosclerosis in mice. Aging (Albany NY). 2016;8:1064-82 pubmed publisher
    ..the expression of multiple atherosclerosis-related genes, including proatherogenic gene TNFSF4 (tumor necrosis factor superfamily member 4)...
  75. Sitrin J, Suto E, Wuster A, Eastham Anderson J, Kim J, Austin C, et al. The Ox40/Ox40 Ligand Pathway Promotes Pathogenic Th Cell Responses, Plasmablast Accumulation, and Lupus Nephritis in NZB/W F1 Mice. J Immunol. 2017;199:1238-1249 pubmed publisher
    b>Ox40 ligand (Ox40L) locus genetic variants are associated with the risk for systemic lupus erythematosus (SLE); however, it is unclear how Ox40L contributes to SLE pathogenesis...
  76. Tian L, Guo W, Yuan Z, Lui V, Chan J, Yagita H, et al. Association of the CD134/CD134L costimulatory pathway with acute rejection of small bowel allograft. Transplantation. 2002;74:133-8 pubmed
    The CD134/CD134L interaction provides a strong costimulatory signal that is CD28-independent...
  77. Serghides L, Bukczynski J, Wen T, Wang C, Routy J, Boulassel M, et al. Evaluation of OX40 ligand as a costimulator of human antiviral memory CD8 T cell responses: comparison with B7.1 and 4-1BBL. J Immunol. 2005;175:6368-77 pubmed
    ..Thus, OX40L costimulates human antiviral memory CD8 T cell responses largely through indirect effects and can enhance anti-influenza, anti-EBV, and anti-HIV responses, particularly in combination with 4-1BBL or B7. ..
  78. Liu D, Yan J, Wang C, Chen G, Ding S, Liu P, et al. The clinical implications of increased OX40 ligand expression in patients with acute coronary syndrome. Clin Chim Acta. 2008;397:22-6 pubmed publisher
    Increasing evidence show that OX40 ligand (OX40L), also known as tumor necrosis factor superfamily member 4 (TNFSF4), plays an important role in the pathogenesis of atherosclerosis...
  79. Torii Y, Ito T, Amakawa R, Sugimoto H, Amuro H, Tanijiri T, et al. Imidazoquinoline acts as immune adjuvant for functional alteration of thymic stromal lymphopoietin-mediated allergic T cell response. J Immunol. 2008;181:5340-9 pubmed
    ..TSLP) and human DCs plays an essential role in evoking inflammatory Th2 responses in allergy through OX40 ligand expression on DCs...
  80. Kimman T, Banus S, Reijmerink N, Reimerink J, Stelma F, Koppelman G, et al. Association of interacting genes in the toll-like receptor signaling pathway and the antibody response to pertussis vaccination. PLoS ONE. 2008;3:e3665 pubmed publisher
    ..Fine tuning of interacting proteins in the TLR pathway appears important for the induction of an optimal vaccine response. ..
  81. Zhang S, Han J, Sun L, Lu W, Yin X, Zhang X, et al. A single-nucleotide polymorphism of the TNFSF4 gene is associated with systemic lupus erythematosus in Chinese Han population. Rheumatol Int. 2011;31:227-31 pubmed publisher
    ..Our study not only suggested that the TNFSF4 gene was associated with SLE in Chinese Han population, but also implied that it might be a common genetic factor predisposing to the development of SLE in multiple populations. ..
  82. Orozco G, Eyre S, Hinks A, Bowes J, Morgan A, Wilson A, et al. Study of the common genetic background for rheumatoid arthritis and systemic lupus erythematosus. Ann Rheum Dis. 2011;70:463-8 pubmed publisher
    ..8% of the genetic susceptibility to RA as a whole. The findings confirm the association of the BLK and UBE2L3 loci with RA, thus adding to the list of loci showing overlap between RA and SLE. ..
  83. Chen M, CHENG G, Ma L, Wang H, Qiu R, Xue F, et al. [Association study between TNFSF4 and coronary heart disease]. Yi Chuan. 2011;33:239-45 pubmed
    ..0173)). In principal component score-based logistic regression analysis, the first principal component has statistical significance (P=0.0236). These results indicate that TNFSF4 is a susceptibility gene of CHD in Chinese Han population. ..
  84. Zhu R, Jiang J, Wang T, Xu T, Wu M, Liu C, et al. [Expressions and clinical significance of OX40 and OX40L in peripheral blood of patients with primary Sjogren's syndrome]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2013;29:862-5 pubmed
    ..The high levels of OX40 and OX40L expression were significantly correlated with clinical outcome and therapeutic response, suggesting that OX40/OX40L pathway may play a critical role in pSS pathogenesis. ..
  85. Zuo X, Sheng Y, Hu S, Gao J, Li Y, Tang H, et al. Variants in TNFSF4, TNFAIP3, TNIP1, BLK, SLC15A4 and UBE2L3 interact to confer risk of systemic lupus erythematosus in Chinese population. Rheumatol Int. 2014;34:459-64 pubmed publisher
    ..06E-14) and the BLK and SLC15A4 SNPs (P adjusted = 4.51E-12). These results may contribute to our understanding of SLE genetic interactions and account for the additional risk of certain patients to develop SLE. ..
  86. Laustsen J, Rasmussen T, Stengaard Pedersen K, Hørslev Petersen K, Hetland M, Østergaard M, et al. Soluble OX40L is associated with presence of autoantibodies in early rheumatoid arthritis. Arthritis Res Ther. 2014;16:474 pubmed publisher
    ..Combined, these findings could reflect that increased activity in the OX40 systems facilitate to drive disease activity and autoantibody production in RA. Clincaltrials.gov NCT00660647, 10 April 2008. ..
  87. Fu Y, Huang W, Jin D, Geng D. Association of TNFSF4 (rs3850641) gene polymorphisms and coronary heart disease: an evidence-based meta-analysis. Int J Clin Pharmacol Ther. 2016;54:354-61 pubmed publisher
    ..This meta-analysis reveals that TNFSF4 (rs3850641) polymorphisms is not associated with CHD risk. ..
  88. Chen J, Li J, Zhao S, Wang D, Zhang W, Liang W. Clinical significance of costimulatory molecules CD40/CD40L and CD134/CD134L in coronary heart disease: A case-control study. Medicine (Baltimore). 2017;96:e7634 pubmed publisher
    The aim of the study was to evaluate the potential role of CD40/CD40 ligand (CD40L) and CD134/CD134 ligand (CD134L) in the development of coronary heart disease (CHD) via the performance of a case-control study...
  89. Shi J, Wang L, Zhu Y, Zhao C, Liu W, Jiang S, et al. OX40 ligand levels and high-sensitivity C-reactive protein levels in blood from local coronary plaque and the femoral artery in patients with acute coronary syndrome or stable angina. J Int Med Res. 2011;39:1275-83 pubmed
    b>OX40 ligand (OX40L) and high-sensitivity C-reactive protein (hs-CRP) play important roles in the pathogenesis of atherosclerosis...
  90. Lu M, Xu W, Yang J, Ye Q, Feng C, Li J, et al. Association of TNFSF4 polymorphisms with systemic lupus erythematosus: a meta-analysis. Mod Rheumatol. 2013;23:686-93 pubmed publisher
    To more precisely estimate the association between the tumor necrosis factor ligand superfamily member 4 (TNFSF4) gene polymorphisms and systemic lupus erythematosus (SLE) risk, we surveyed studies on the association of the TNFSF4 ..
  91. Jacquemin C, Schmitt N, Contin Bordes C, Liu Y, Narayanan P, Seneschal J, et al. OX40 Ligand Contributes to Human Lupus Pathogenesis by Promoting T Follicular Helper Response. Immunity. 2015;42:1159-70 pubmed publisher
    ..However, the mechanisms that cause aberrant Tfh cell responses in SLE remain elusive. Here we showed the OX40 ligand (OX40L)-OX40 axis contributes to the aberrant Tfh response in SLE...
  92. Cortini A, Ellinghaus U, Malik T, Cunninghame Graham D, Botto M, VYSE T. B cell OX40L supports T follicular helper cell development and contributes to SLE pathogenesis. Ann Rheum Dis. 2017;76:2095-2103 pubmed publisher
    ..Blockade of OX40L has been demonstrated to reduce disease severity in several models of autoimmunity, but not in SLE. We sought to investigate its potential therapeutic role in lupus...