Abstract
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.
Highlights
Numerous biological phenomena exhibit distinctive traits due to sexual dimorphism
Similar changes were observed in Wi weights at sacrifice, and in visceral and subcutaneous adipose tissue volumes analyzed by magnetic resonance imaging (MRI) at 12 weeks of high-fat diet (HFD) feeding; Wg weights at sacrifice were almost similar among the three groups of HFD-fed mice (Fig 1I–1M)
VO2 in the dark phase, and VCO2 in both light and dark phases decreased in the HFD-fed female mice
Summary
Numerous biological phenomena exhibit distinctive traits due to sexual dimorphism. Immune and metabolic systems are representative because they are markedly affected by sex hormones [1, 2]. As systemic metabolism is regulated by immune systems, their coordinated association has been explored in immuno-metabolism studies. Obesity-associated infiltration of immune cells promotes chronic inflammation, especially in visceral adipose tissue, and exacerbates insulin resistance and glucose metabolism [3, 4].
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