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

Do Hyun Kim, Hong Jai Park, Hyeon Soo Park, Jae Ung Lee, Che Myong Ko, Myung Chan Gye, Je Min Choi

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number41
JournalExperimental and Molecular Medicine
Volume51
Issue number4
DOIs
StatePublished - Apr 1 2019

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T-cells
Estrogen Receptor alpha
Helper-Inducer T-Lymphocytes
Autoimmunity
Estrogen Receptors
T-Lymphocytes
CD4 Antigens
Knockout Mice
Immunoglobulin Class Switching
Germinal Center
Gonadal Steroid Hormones
Autoantibodies
Estrogens
Immunization
Th17 Cells
Th2 Cells
Th1 Cells
Antibodies
Immunoglobulin Isotypes
Ovalbumin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Estrogen receptor α in T cells suppresses follicular helper T cell responses and prevents autoimmunity. / Kim, Do Hyun; Park, Hong Jai; Park, Hyeon Soo; Lee, Jae Ung; Ko, Che Myong; Gye, Myung Chan; Choi, Je Min.

In: Experimental and Molecular Medicine, Vol. 51, No. 4, 41, 01.04.2019.

Research output: Contribution to journalArticle

Kim, Do Hyun ; Park, Hong Jai ; Park, Hyeon Soo ; Lee, Jae Ung ; Ko, Che Myong ; Gye, Myung Chan ; Choi, Je Min. / Estrogen receptor α in T cells suppresses follicular helper T cell responses and prevents autoimmunity. In: Experimental and Molecular Medicine. 2019 ; Vol. 51, No. 4.
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