Capicua deficiency induces autoimmunity and promotes follicular helper T cell differentiation via derepression of ETV5.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28855737.
- Also identified by DOI 10.1038/ncomms16037 and PMC identifier 5510180.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sub>FH</sub>) 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<sub>FH</sub> cells and GC responses in a T-cell-intrinsic manner. ETV5 expression is derepressed in Cic null T<sub>FH</sub> cells and knockdown of Etv5 suppresses the enhanced T<sub>FH</sub> cell differentiation in Cic-deficient CD4<sup>+</sup> T cells, suggesting that Etv5 is a critical CIC target gene in T<sub>FH</sub> 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<sub>FH</sub> cell development and autoimmunity.
Medical subject headings
- Autoimmunity
- DNA-Binding Proteins
- Germinal Center
- Repressor Proteins
- T-Lymphocytes, Helper-Inducer
- Transcription Factors