Estrogen regulates sex-specific localization of regulatory T cells in adipose tissue of obese female mice
Estrogen regulates sex-specific localization of regulatory T cells in adipose tissue of obese female mice
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DOI：
10.1371/journal.pone.0230885
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发表时间：
2020-04-02
期刊：
影响因子：
3.7
通讯作者：
Sasaoka, Toshiyasu
中科院分区：
文献类型：
--
作者：
Ishikawa, Akari;Wada, Tsutomu;Sasaoka, Toshiyasu
调节性T细胞（Treg）在维持免疫稳态方面发挥着重要作用。在雄性肥胖小鼠中，内脏脂肪组织中的常驻Treg（VAT-Treg）减少，这导致肥胖相关的慢性炎症和胰岛素抵抗的发展。尽管已经报道了免疫应答的性别差异，但代谢环境的差异对VAT-Treg的影响尚不清楚。我们研究了VAT-Treg在雌性小鼠中的定位，并与在雄性小鼠中的定位进行比较。在高脂饮食（HFD）中，雄性小鼠的VAT-Treg减少，但雌性小鼠增加。这种增加在卵巢切除和HFD喂养的小鼠中被消除，但通过补充雌激素恢复。IL 33受体ST 2对于雄性中VAT-Treg的定位和成熟是重要的，在从两种性别的肥胖小鼠的性腺脂肪中分离的CD 4（+）CD 25（+）T细胞中减少，表明雌性中存在不同的VAT-Treg定位系统。对性腺脂肪和脂肪CD 4（+）CD 25（+）T细胞中趋化因子表达的广泛分析揭示了与女性特异性VAT-Treg积累相关的几种趋化因子信号，如CCL 24、CCR 6和CXCR 3。综上所述，本研究证明了肥胖小鼠中VAT-Treg定位的性二态性。雌激素可能部分通过改变女性中趋化因子相关的VAT-Treg定位来减轻肥胖相关的慢性炎症。
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.