A contribution of FcγRIIIa cosignaling in TFHsubset development in Systemic Lupus Erythematosus

Background Expansion of follicular helper T cells (T FH ) 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 (Fc γ RIIIa costimulation) play in T FH cells development. Methods We examined the presence of blood T FH 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 Fc γ RIIIa and compared to CD28 cosignaling. Results In 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 T FH population markers. In vitro activation from plate-bound ICs of human naïve CD4 + T cells results in the differentiation of T FH like cells phenotype. We show that Fc γ RIIIa-pSyk cosignaling in Bcl6 + IL-21 + cells drives the production of both IFN- γ (T FH 1) and IL-17A (T FH 17) production. TLR9 engagement by CpG ODN 2006 combined with Fc γ RIIIa costimulation of CD4 + T cells augments, IL-17A, IL-21 production in Bcl6 + T cells. Fc γ RIIIa cosignaling induced the overexpression of microRNAs that participate in TLR signaling and are associated with T FH cell differentiation. RNA-seq data reveal pathways that may contribute to the development of T FH cells and nucleic acid sensing. Conclusion Our results suggest a role for Fc γ RIIIa receptors in T FH development and a role for nucleic acid sensing in the expansion of T FH cells.