Negatively charged phospholipids suppress IFN-γ production in T cells

The effect of phospholipids on IFN-γ production in mouse T cells was investigated. Phosphatidylserine (PS), which has a negatively charged head group, completely inhibited IFN-γ production in splenic naïve T cells and antigen-dependent IFN-γ production in Th1 clone 42-6A cells, whereas other phospholipids, which have neutrally charged head group, had no effect. The structural requirements for IFN-γ inhibitory effects by PS were investigated, and dimyristoyl-PS (C14: 0) and dipalmitoyl-PS (C16: 0) had no effect on IFN-γ production, and interestingly, distearoyl-PS (18: 0) increased IFN-γ production. Dioleoyl-PS (C18: 1), dilinoleoyl-PS (C18: 2), and oleoyl-lyso-PS (C18: 1) completely inhibited IFN-γ production. To clarify this mechanism, we focused on the stability of IFN-γ mRNA, and the treatment of splenic naïve T cells with PS brought about 40% reductions in IFN-γ mRNA expression in the presence of actinomycin D. Collectively, IFN-γ inhibitory effects by PS are highly dependent on the molecular structure of PS and involve the decreasing of the stability of IFN-γ mRNA.