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The pro-inflammatory effect of triglyceride on human CD4+ T cells and experimental autoimmune uveitis

Tan, S;Feng, X;Liu, Z;Wang, Q;Jiang, Q;Ye, X;Li, H;Su, G;Zhou, C;Wang, Y;Yang, P;

Aberrant lipid metabolism plays a role in inflammation and progression of autoimmune diseases but the definite mechanism remains unclear. In this study we investigate lipidomic profiles in Beh├žet’s disease (BD) and the role of triglyceride (TAG) in the pathogenesis of autoimmune uveitis. Lipidomics revealed a distinct lipid metabolite profile including increased TAG metabolites in plasma of active BD patients. TAG could stimulate the proliferation, IL-17 and IFN-? expression by CD4+ T cells and Th1, Th17 cell differentiation in vitro, but did not influence neutrophils. A922500 inhibited the TAG generation, ameliorated the EAU severity, decreased Th17 frequency and IL-17 expression by CD4+ T cells in vivo. The proteomocis analysis showed an up-regulation of apoptosis-related protein, Pik3r2, in CD4+ T cells from A922500-treated mice. In conclusion, TAG can stimulate human CD4+ T cells and the inhibition of its generation could significantly ameliorate EAU activity in association with down-regulated Th17 cell response.