Capicua deficiency induces autoimmunity and promotes follicular helper T cell differentiation via derepression of ETV5

High-affinity antibody production through the germinal centre (GC) response is a pivotal process in adaptive immunity. Abnormal development of follicular helper T (T FH ) cells can induce the GC response to self-antigens, subsequently leading to autoimmunity. Here we show the transcriptional repressor Capicua/CIC maintains peripheral immune tolerance by suppressing aberrant activation of adaptive immunity. CIC deficiency induces excessive development of T FH cells and GC responses in a T-cell-intrinsic manner. ETV5 expression is derepressed in Cic null T FH cells and knockdown of Etv5 suppresses the enhanced T FH cell differentiation in Cic -deficient CD4 + T cells, suggesting that Etv5 is a critical CIC target gene in T FH cell differentiation. Furthermore, we identify Maf as a downstream target of the CIC–ETV5 axis in this process. These data demonstrate that CIC maintains T-cell homeostasis and negatively regulates T FH cell development and autoimmunity. Follicular helper T (T FH ) cells promote germinal centre (GC) response for efficient generation of protective antibodies during humoral immunity. Here the authors show that deficiency of the translational repressor, Capicua/CIC, enhances T FH differentiation and GC responses potentially via the derepression of Etv5 .