Target Validation Information
Target ID T92124
Target Name Tumor necrosis factor receptor superfamily member 4
Target Type
Clinical Trial
Action against Disease Model R4930 Blockade of interactions between OX40 on Th2 cells and OX40 ligand (OX40L) on TSLP-activated DCs using an OX40L-specific monoclonal antibody, inhibited Th2 cell-mediated immune responses in both mouse and nonh uMan primate models of allergic inflammation. [552761] Drug Info
The Effect of Target Knockout, Knockdown or Genetic Variations We examined apolipoprotein E-deficient (ApoE(-/-)) mice and ApoE(-/-)/OX40L-double-deficient (ApoE(-/-)/OX40L(-/-)) mice fed on a high-fat diet for 8 weeks. The extent of aorticatheroma was significantly less in ApoE(-/-)/OX40L(-/-) mice compared with ApoE(-/-) mice. We also treated high-fat-fed ApoE(-/-) mice with or without MGP34 antibody (OX40L-specific neutralizing antibody) for 10 weeks. After the treatment, the extent of aortic atheroma was again significantly less in MGP34-treated mice compared with controls. Importantly, both vascular density in the aortic adventitia and vascular endothelial growth factor-induced angiogenesis in the Matrigel assay in vivo were significantly reduced in ApoE(-/-)/OX40L(-/-) mice compared with ApoE(-/-) mice. Finally, when high-fat-fed ApoE(-/-) mice were transplanted with bone marrow cells from either wild-type or OX40L(-/-) mice, the extent of aortic atheroma was comparable between the two groups.These results indicate that the vascular OX40/OX40L system plays an important role in the formation of vasa vasor uM and subsequent atherosclerosis, suggesting that the vascular OX40/OX40L system might be a new therapeutic target of atherosclerosis [552761]
References
Ref 552761OX40-OX40L interactions: a promising therapeutic target for allergic diseases? J Clin Invest. 2007 Dec;117(12):3655-7.

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