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

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Title
Capicua deficiency induces autoimmunity and promotes follicular helper T cell differentiation via derepression of ETV5
Author(s)
Sungjun Park; Seungwon Lee; Choong-Gu Lee; Guk Yeol Park; Hyebeen Hong; Jeon-Soo Lee; Young Min Kim; Sung Bae Lee; Daehee Hwang; Youn Soo Choi; John D. Fryer; Sin-Hyeog Im; Seung-Woo Lee; Yoontae Lee
Publication Date
2017-07
Journal
NATURE COMMUNICATIONS, v.8, no., pp.16037 -
Publisher
NATURE PUBLISHING GROUP
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. © The Author(s) 2017
URI
http://pr.ibs.re.kr/handle/8788114/3815
DOI
10.1038/ncomms16037
ISSN
2041-1723
Appears in Collections:
Center for Plant Aging Research (식물 노화·수명 연구단) > Journal Papers (저널논문)
Academy of Immunology and Microbiology(면역 미생물 공생 연구단) > Journal Papers (저널논문)
Files in This Item:
10.Capicua deficiency induces autoimmunity and promotes follicular helper T cell differentiation via derepression of ETV5_Nature Comm.pdfDownload

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