A contribution of FcγRIIIa cosignaling in TFH subset development in Systemic Lupus Erythematosus

Author:

Chauhan Anil K

Abstract

AbstractBackgroundExpansion of follicular helper T cells (TFH) population occurs in systemic lupus erythematosus (SLE) and their numbers correlate with autoantibody titers. In this study, we sought to examine the role of ICs (FcγRIIIa costimulation) play in TFH cells development.MethodsWe examined the presence of blood TFH cells using multicolor flow analysis in SLE patients in vivo. We then examined the development of these cells in vitro using plate-bound ICs. Performed differential expression analysis in cells activated via FcγRIIIa and compared to CD28 cosignaling.ResultsIn SLE patients PBMCs, CD4+ gated T cells show IC binding and phosphorylated spleen tyrosine kinase (pSyk). These pSyk+ cells express PD1, ICOS, IL-21, and Bcl6, the TFH population markers. In vitro activation from plate-bound ICs of human naïve CD4+ T cells results in the differentiation of TFH like cells phenotype. We show that FcγRIIIa-pSyk cosignaling in Bcl6+IL-21+ cells drives the production of both IFN-γ (TFH1) and IL-17A (TFH17) production. TLR9 engagement by CpG ODN 2006 combined with FcγRIIIa costimulation of CD4+ T cells augments, IL-17A, IL-21 production in Bcl6+ T cells. FcγRIIIa cosignaling induced the overexpression of microRNAs that participate in TLR signaling and are associated with TFH cell differentiation. RNA-seq data reveal pathways that may contribute to the development of TFH cells and nucleic acid sensing.ConclusionOur results suggest a role for FcγRIIIa receptors in TFH development and a role for nucleic acid sensing in the expansion of TFH cells.

Publisher

Cold Spring Harbor Laboratory

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