TRAF3 regulates IL-6 receptor signaling in T cells through the phosphatase PTPN22

Abstract IL-6 is an important signal three cytokine for T helper 17 (Th17) and follicular (Tfh) differentiation. Previous work has suggested a possible role TRAF3 in the function and/or differentiation of these two subsets, but no direct studies have yet been performed. In this study, we examine IL-6R signaling cells. regulates IL-2R type I interferon receptor cells by altering recruitment phosphatases PTPN2 PTPN22, respectively. B cell curtails recruiting thus hypothesized that through PTPN22-dependent mechanism. We investigated using TRAF3-deficient human lymphoma line from cell-specific knockout mouse (T-Traf3−/−). found reduced IL-6-induced STAT1 STAT3 activation are both required full Tfh cells, whereas antagonizes Th17 Interestingly, vitrodifferentiation naïve CD4 to was not affected deficiency. To determine mechanism which promotes response signaling, treated WT Traf3−/−T with presence PTPN22 inhibitor or vehicle control. inhibition restored STAT3, did restore STAT1, suggesting different mechanisms regulation. Together data implicate regulation partly manner, lending additional level understanding Supported NIH R01 AI123107, AI162656, T32 AI007260