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

Article scientifique 2017 Anglais

Résumé

Abstract High-affinity antibody production through the germinal centre (GC) response is a pivotal process in adaptive immunity. Abnormal development of follicular helper T (TFH) 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 TFH cells and GC responses in a T-cell-intrinsic manner. ETV5 expression is derepressed in Cic null TFH cells and knockdown of Etv5 suppresses the enhanced TFH cell differentiation in Cic-deficient CD4+ T cells, suggesting that Etv5 is a critical CIC target gene in TFH 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 TFH cell development and autoimmunity.

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Park, S., Lee, S., Lee, C., Park, G., Hong, H., Lee, J., Hwang, D., Choi, Y., Fryer, J., Im, S., Lee, S., Lee, Y. (2017). Capicua deficiency induces autoimmunity and promotes follicular helper T cell differentiation via derepression of ETV5. https://doi.org/10.1038/ncomms16037

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Auteur(s)

Sung Jun Park Seungwon Lee Choong‐Gu Lee Guk Yeol Park Hyebeen Hong Jeon-Soo Lee Daehee Hwang Youn Soo Choi John Denis Fryer Sin‐Hyeog Im Seung‐Woo Lee Yoontae Lee

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