Sex-specific adipose tissue imprinting of regulatory T cells.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Adipose tissue is an energy store and a dynamic endocrine organ 1,2 . In particular, visceral adipose tissue (VAT) is critical for the regulation of systemic metabolism 3,4 . Impaired VAT function-for example, in obesity-is associated with insulin resistance and type 2 diabetes 5,6 . Regulatory T (T reg ) cells that express the transcription factor FOXP3 are critical for limiting immune responses and suppressing tissue inflammation, including in the VAT 7-9 . Here we uncover pronounced sexual dimorphism in T reg cells in the VAT. Male VAT was enriched for T reg cells compared with female VAT, and T reg cells from male VAT were markedly different from their female counterparts in phenotype, transcriptional landscape and chromatin accessibility. Heightened inflammation in the male VAT facilitated the recruitment of T reg cells via the CCL2-CCR2 axis. Androgen regulated the differentiation of a unique IL-33-producing stromal cell population specific to the male VAT, which paralleled the local expansion of T reg cells. Sex hormones also regulated VAT inflammation, which shaped the transcriptional landscape of VAT-resident T reg cells in a BLIMP1 transcription factor-dependent manner. Overall, we find that sex-specific differences in T reg cells from VAT are determined by the tissue niche in a sex-hormone-dependent manner to limit adipose tissue inflammation.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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