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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
LEE, YOONTAEPark, SLee, SLee, C.-GPark, G.YHong, HLee, J.-SKim, Y.MLee, S.BHwang, DChoi, Y.SFryer, J.DIm, S.-HLee, S.-W
POSTECH Authors
LEE, YOONTAE
Date Issued
Jul-2017
Publisher
NPG
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.
URI
http://oasis.postech.ac.kr/handle/2014.oak/39060
DOI
10.1038/ncomms16037
ISSN
2041-1723
Article Type
Article
Citation
Nature Communications, vol. 8, page. 16037, 2017-07
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 LEE, YOONTAE
Dept of Life Sciences
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