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调节性T细胞性别特异性脂肪组织印迹
2020-02-27 15:37

澳大利亚墨尔本大学Axel Kallies和Ajithkumar Vasanthakumar合作的最新研究揭示了调节性T(Treg)细胞性别特异性脂肪组织印迹。这一研究成果在线发表在2020年2月26日出版的《自然》杂志上。

研究人员发现在内脏脂肪组织(VAT)中,Treg细胞呈明显的性二态性。与雌性VAT相比,雄性VAT富集了Treg细胞,并且雄性VAT中Treg细胞在表型、转录图谱和染色质可及性方面与其相对应的雌性明显不同。雄性VAT中炎症加剧,其通过CCL2-CCR2通路促进Treg细胞的招募。在雄性VAT中,雄激素调节特异性产生IL-33的基质细胞群分化,这与Treg细胞的局部扩增平行。性激素还调节VAT炎症,以BLIMP1转录因子依赖性方式重塑了VAT驻留Treg细胞的转录图谱。总体而言,该研究发现VAT中性别特异性差异的Treg细胞是由组织龛中性激素依赖的方式决定的,以抑制脂肪组织炎症。

据介绍,脂肪组织是能量存储和动态内分泌器官。尤其是内脏脂肪组织对于调节全身代谢至关重要。例如,在肥胖症患者中VAT功能受损与胰岛素抵抗和2型糖尿病相关。表达转录因子FOXP3的Treg细胞对于限制免疫应答和抑制组织炎症至关重要,包括在VAT中。

附:英文原文

Title: Sex-specific adipose tissue imprinting of regulatory T cells

Author: Ajithkumar Vasanthakumar, David Chisanga, Jonas Blume, Renee Gloury, Kara Britt, Darren C. Henstridge, Yifan Zhan, Santiago Valle Torres, Sebastian Liene, Nicholas Collins, Enyuan Cao, Tom Sidwell, Chaoran Li, Raul German Spallanzani, Yang Liao, Paul A. Beavis, Thomas Gebhardt, Natalie Trevaskis, Stephen L. Nutt, Jeffrey D. Zajac, Rachel A. Davey, Mark A. Febbraio, Diane Mathis, Wei Shi, Axel Kallies

Issue&Volume: 2020-02-26

Abstract: Adipose tissue is an energy store and a dynamic endocrine organ1,2. In particular, visceral adipose tissue (VAT) is critical for the regulation of systemic metabolism3,4. Impaired VAT function—for example, in obesity—is associated with insulin resistance and type 2 diabetes5,6. Regulatory T (Treg) cells that express the transcription factor FOXP3 are critical for limiting immune responses and suppressing tissue inflammation, including in the VAT7,8,9. Here we uncover pronounced sexual dimorphism in Treg cells in the VAT. Male VAT was enriched for Treg cells compared with female VAT, and Treg 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 Treg 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 Treg cells. Sex hormones also regulated VAT inflammation, which shaped the transcriptional landscape of VAT-resident Treg cells in a BLIMP1 transcription factor-dependent manner. Overall, we find that sex-specific differences in Treg cells from VAT are determined by the tissue niche in a sex-hormone-dependent manner to limit adipose tissue inflammation.

DOI: 10.1038/s41586-020-2040-3

Source: https://www.nature.com/articles/s41586-020-2040-3

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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