Estrogen regulates sex-specific localization of regulatory T cells in adipose tissue of obese female mice

Akari Ishikawa, Tsutomu Wada*, Sanshiro Nishimura, Tetsuo Ito, Akira Okekawa, Yasuhiro Onogi, Eri Watanabe, Azusa Sameshima, Tomoko Tanaka, Hiroshi Tsuneki, Shigeru Saito, Toshiyasu Sasaoka

*この論文の責任著者

研究成果: ジャーナルへの寄稿学術論文査読

32 被引用数 (Scopus)

抄録

Regulatory T cells (Treg) play essential roles in maintaining immune homeostasis. Resident Treg in visceral adipose tissue (VAT-Treg) decrease in male obese mice, which leads to the development of obesity-associated chronic inflammations and insulin resistance. Although gender differences in immune responses have been reported, the effects of the difference in metabolic environment on VAT-Treg are unclear. We investigated the localization of VAT-Treg in female mice in comparison with that in male mice. On a high-fat diet (HFD), VAT-Treg decreased in male mice but increased in female mice. The increase was abolished in ovariectomized and HFD-fed mice, but was restored by estrogen supplementation. The IL33 receptor ST2, which is important for the localization and maturation of VAT-Treg in males, was reduced in CD4+CD25+ T cells isolated from gonadal fat of obese mice of both genders, suggesting that a different system exists for VAT-Treg localization in females. Extensive analysis of chemokine expression in gonadal fat and adipose CD4+CD25+T cells revealed several chemokine signals related to female-specific VAT-Treg accumulation such as CCL24, CCR6, and CXCR3. Taken together, the current study demonstrated sexual dimorphism in VAT-Treg localization in obese mice. Estrogen may attenuate obesity-associated chronic inflammation partly through altering chemokine-related VAT-Treg localization in females.

本文言語英語
論文番号e0230885
ジャーナルPLoS ONE
15
4
DOI
出版ステータス出版済み - 2020

ASJC Scopus 主題領域

  • 一般

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