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Estrogen receptor α in T cells suppresses follicular helper T cell responses and prevents autoimmunity

Title
Estrogen receptor α in T cells suppresses follicular helper T cell responses and prevents autoimmunity
Author
계명찬
Keywords
IMMUNE-RESPONSE; B-CELLS; DIFFERENTIATION; EXPRESSION; ANTIGEN; ENCEPHALOMYELITIS; LYMPHOCYTES; MACROPHAGES; INHIBITION; DEFICIENCY
Issue Date
2019-04
Publisher
NATURE PUBLISHING GROUP
Citation
EXPERIMENTAL AND MOLECULAR MEDICINE, v. 51, no. 41
Abstract
Estrogen receptor alpha (ERα) is a sex hormone nuclear receptor that regulates various physiological events, including the immune response. Although there have been some recent studies on ERα regarding subsets of T cells, such as Th1, Th2, Th17, and Treg cells, its role in follicular helper T (TFH) cells has not yet been elucidated. To determine whether ERα controls TFH response and antibody production, we generated T cell-specific ERα knockout (KO) mice by utilizing the CD4-Cre/ERα flox system (CD4-ERα KO) and then analyzed their phenotype. At approximately 1 year of age, CD4- ERα KO mice spontaneously showed mild autoimmunity with increased autoantibody production and CD4+CD44+CXCR5+Bcl-6+ TFH cells in the mesenteric lymph nodes and spleen. We next immunized 6–8-week-old CD4-ERα KO mice with sheep red blood cells (SRBCs), which resulted in an increased proportion of TFH cells and germinal center (GC) responses. In addition, 17β-estradiol (E2) treatment decreased TFH responses in wild-type mice and suppressed the mRNA expression of Bcl-6 and IL-21. Finally, we confirmed that the production of high-affinity antigen-specific antibodies and isotype class switching induced by NP-conjugated ovalbumin immunization were elevated in CD4-ERα KO mice under sufficient estrogen conditions. These results collectively demonstrate that the female sex hormone receptor ERα inhibits the TFH cell response and GC reaction to control autoantibody production, which was related to estrogen signaling and autoimmunity.
URI
https://www.nature.com/articles/s12276-019-0237-zhttp://repository.hanyang.ac.kr/handle/20.500.11754/110778
ISSN
1226-3613; 2092-6413
DOI
10.1038/s12276-019-0237-z
Appears in Collections:
COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
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