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

Title
Capicua deficiency induces autoimmunity and promotes follicular helper T cell differentiation via derepression of ETV5
Authors
이충구박성준이승원박국열홍혜빈이전수김영민이성배황대희최윤수John D. Fryer임신혁이승우이윤태
Issue Date
2017-07
Publisher
Nature Communications
Citation
VOL 8-16037-13
Abstract
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.
URI
http://pubs.kist.re.kr/handle/201004/69625
ISSN
2041-1723
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KIST Publication > Article
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