자가면역반응과 여포 보조 T 세포의 분화 과정에서 Capicua 전사 인자의 역할에 관한 연구
- Title
- 자가면역반응과 여포 보조 T 세포의 분화 과정에서 Capicua 전사 인자의 역할에 관한 연구
- Authors
- 박성준
- Date Issued
- 2017
- Publisher
- 포항공과대학교
- Abstract
- High affinity antibody production through the germinal center (GC) responses is a pivotal process in adaptive immunity and dysregulated GC responses have been implicated in the pathogenesis of autoimmune diseases in both human and mice. CD4+ follicular helper T cells (TFH cells) are essential for GC responses and long-lived antibody responses. Abnormal development of TFH cells could induce the GC response to self-antigens, subsequently leading to autoimmunity. Here I report for the first time that the transcriptional repressor Capicua (CIC) is a key factor for maintenance of peripheral immune tolerance by suppressing aberrant activation of adaptive immunity. Loss of CIC causes lymphoproliferative autoimmunity in mice, which is accompanied by augmented T cell responses. CIC deficiency induces spontaneous excessive development of TFH cells and GC response in a T cell-intrinsic manner. Mechanistically, ETV5 expression is de-repressed in Cic null TFH cells and knock-down of Etv5 suppresses the enhanced TFH cell differentiation in Cic deficient CD4+ T cells, suggesting that Etv5 is a critical CIC target gene promoting TFH cell differentiation. Furthermore, I identify c-Maf as a downstream target of CIC-ETV5 axis in this process. Taken together, these data demonstrate that CIC maintains T cell homeostasis and negatively regulates TFH cell development and autoimmunity in mice. In this regard, CIC-ETV5 axis could be evaluated as molecular targets for treatment of autoimmune diseases.
- URI
- http://postech.dcollection.net/jsp/common/DcLoOrgPer.jsp?sItemId=000002374952
https://oasis.postech.ac.kr/handle/2014.oak/92901
- Article Type
- Thesis
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