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Nat Commun. 2017 Jul 12;8:16037. doi: 10.1038/ncomms16037.

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

Author information

1
Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 73673, Republic of Korea.
2
Division of Integrative Bioscience and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk 73673, Republic of Korea.
3
Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Gyeongbuk 73673, Republic of Korea.
4
Department of Brain &Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Republic of Korea.
5
Center for Plant Aging Research, Institute for Basic Science, DGIST, Daegu 42988, Republic of Korea.
6
Department of Biomedical Sciences, Department of Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
7
Transplantation Research Institute, Department of Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
8
Department of Neuroscience, Mayo Clinic, Jacksonville, Florida 32224, USA.

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.

PMID:
28855737
PMCID:
PMC5510180
DOI:
10.1038/ncomms16037
[Indexed for MEDLINE]
Free PMC Article

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