KMID : 0620920190510040041
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Experimental & Molecular Medicine 2019 Volume.51 No. 4 p.41 ~ p.41
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Estrogen receptor ¥á in T cells suppresses follicular helper T cell responses and prevents autoimmunity
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Kim Do-Hyun
Park Hong-Jai Park Hyeon-Soo Lee Jae-Ung Ko Che-Myong Jay Gye Myung-Chan Choi Je-Min
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Abstract
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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?8-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.
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KEYWORD
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Autoimmunity, Follicular T-helper cells
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