Fc{gamma}RIIIa-Syk Co-signal Modulates CD4+ T-cell Response and Up-regulate TLR expression [Cell Biology]

November 18th, 2015 by Chauhan, A. K., Moore, T. L., Bi, Y., Chen, C.

CD4+ T-cells in SLE patients show altered TCR signaling, which utilize FcRγ-Syk. A role for FcγRIIIa activation from immune complex (IC) ligation and sublytic terminal complement complex (C5b-9) in CD4+ T-cell responses is not investigated. In this study, we show that the ICs present in SLE patients by ligating to FcγRIIIa on CD4+ T-cells phosphorylate Syk and provide a co-stimulatory signal to CD4+ T-cells in the absence of CD28 signal. This led to the development of pathogenic IL-17A+ and IFN-γhigh CD4+ T-cells in vitro. Cytokines IL-1β, IL-6, TGF-β1, and IL-23 were the only requirement for the development of both populations. SLE patients CD4+ T-cells that expressed CD25, CD69, and CD98 bound to ICs, showed pSyk, and produced IFN-γ and IL-17A. This FcγRIIIa mediated co-signal differentially up-regulated the expression of IFN pathway genes compared to CD28 co-signal. FcγRIIIa-pSyk up-regulated several TLR genes as well as the HMGB1 and MyD88 gene transcripts. ICs co-localized with these TLR pathway proteins. These results suggest a role for the FcγRIIIa-pSyk signal in modulating adaptive immune responses.