Capicua deficiency induces autoimmunity and promotes follicular helper T cell differentiation via derepression of ETV5
- Capicua deficiency induces autoimmunity and promotes follicular helper T cell differentiation via derepression of ETV5
- 이충구; 박성준; 이승원; 박국열; 홍혜빈; 이전수; 김영민; 이성배; 황대희; 최윤수; John D. Fryer; 임신혁; 이승우; 이윤태
- Issue Date
- Nature Communications
- VOL 8-16037-13
- 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.
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