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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
Park, SungjunLee, SeungwonLee, Choong-GuPark, Guk YeolHong, HyebeenLee, Jeon-SooKim, Young MinLee, Sung BaeHwang, DaeheeChoi, Youn SooFryer, John D.Im, Sin-HyeogLee, Seung-WooLee, Yoontae
DGIST Authors
Lee, Sung BaeHwang, Daehee
Issue Date
2017-07-12
Citation
Nature Communications, 8
Type
Article
Article Type
Article
Keywords
C MAFCenter B CellETS Transcription FactorsExpressionFamilyGerminal Center ResponseIn VivoInterferon GammaRepressor CapicuaTransgenic Mice
ISSN
2041-1723
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://hdl.handle.net/20.500.11750/4130
DOI
10.1038/ncomms16037
Publisher
Nature Publishing Group
Related Researcher
  • Author Lee, Sung Bae SB LAB(Lab of Neurodegenerative diseases and Aging)
  • Research Interests Cellular mechanism of neurodegenerative diseases; Neuronal maintenance and remodeling; 퇴행성 뇌질환의 세포기전; 신경계 유지 및 리모델링 연구
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Collection:
Brain and Cognitive SciencesETC1. Journal Articles
ETC1. Journal Articles


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