IL-12 drives the differentiation of human T follicular regulatory cells

Abstract T follicular regulatory (Tfr) cells can counteract the B cell-helper activity of helper (Tfh) and hinder production antibodies against self-antigens or allergens. A mechanistic understanding cues initiating differentiation (Treg) into Tfr cells, which is instrumental for therapeutic manipulation diseases associated with a cell imbalance, still missing. Despite their opposed roles, Tfh appears to be controlled by partially overlapping signals, including TCR stimulation costimulatory molecules. However, it unknown if cytokines that have been shown control biology human IL-12 activin A, influence cells. To address this question, we evaluated impact these two on in vitro Herein, report role driving, activated Treg induction molecules belong program, CXCR5, PD-1, BCL6 ICOS meanwhile preserving function. Conversely, presented largely negligible effect Tfr-like only modestly strengthened IL-12-driven Importantly, patients inborn errors immunity IL12RB1 gene severe decrease circulating produced higher levels anti-actin autoantibodies vivo. Overall, study unveils as an inducer vivo provides novel approach generation AI123738