407 301

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

Title
Estrogen receptor alpha in T cells suppresses follicular helper T cell responses and prevents autoimmunity
Author
최제민
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 (ER alpha) is a sex hormone nuclear receptor that regulates various physiological events, including the immune response. Although there have been some recent studies on ER alpha 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 ER alpha controls TFH response and antibody production, we generated T cell-specific ER alpha knockout (KO) mice by utilizing the CD4-Cre/ER alpha flox system (CD4-ER alpha KO) and then analyzed their phenotype. At approximately 1 year of age, CD4-ER alpha 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-ER alpha KO mice with sheep red blood cells (SRBCs), which resulted in an increased proportion of TFH cells and germinal center (GC) responses. In addition, 17 beta-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-ER alpha KO mice under sufficient estrogen conditions. These results collectively demonstrate that the female sex hormone receptor ER alpha 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-zhttps://repository.hanyang.ac.kr/handle/20.500.11754/110779
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
Files in This Item:
Estrogen receptor alpha in T cells suppresses follicular helper T cell responses and prevents autoimmunity.pdfDownload
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE