%0 Journal Article
%T Estrogen receptor ¦Á in T cells suppresses follicular helper T cell responses and prevents autoimmunity
%J -
%D 2019
%R https://doi.org/10.1038/s12276-019-0237-z
%X Estrogen receptor alpha (ER¦Á) is a sex hormone nuclear receptor that regulates various physiological events, including the immune response. Although there have been some recent studies on ER¦Á 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¦Á controls TFH response and antibody production, we generated T cell-specific ER¦Á knockout (KO) mice by utilizing the CD4-Cre/ER¦Á flox system (CD4-ER¦Á KO) and then analyzed their phenotype. At approximately 1 year of age, CD4-ER¦Á 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¨C8-week-old CD4-ER¦Á 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¦Â-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¦Á KO mice under sufficient estrogen conditions. These results collectively demonstrate that the female sex hormone receptor ER¦Á inhibits the TFH cell response and GC reaction to control autoantibody production, which was related to estrogen signaling and autoimmunity
%U https://www.nature.com/articles/s12276-019-0237-z