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

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 Behçet'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-γ 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.