調節性T細胞性別特異性脂肪組織印跡
作者：
小柯機器人發布時間：2020/2/27 15:37:07
澳大利亞墨爾本大學Axel Kallies和Ajithkumar Vasanthakumar合作的最新研究揭示了調節性T（Treg）細胞性別特異性脂肪組織印跡。這一研究成果在線發表在2020年2月26日出版的《自然》雜誌上。
研究人員發現在內臟脂肪組織（VAT）中，Treg細胞呈明顯的性二態性。與雌性VAT相比，雄性VAT富集了Treg細胞，並且雄性VAT中Treg細胞在表型、轉錄圖譜和染色質可及性方面與其相對應的雌性明顯不同。雄性VAT中炎症加劇，其通過CCL2-CCR2通路促進Treg細胞的招募。在雄性VAT中，雄激素調節特異性產生IL-33的基質細胞群分化，這與Treg細胞的局部擴增平行。性激素還調節VAT炎症，以BLIMP1轉錄因子依賴性方式重塑了VAT駐留Treg細胞的轉錄圖譜。總體而言，該研究發現VAT中性別特異性差異的Treg細胞是由組織龕中性激素依賴的方式決定的，以抑制脂肪組織炎症。
據介紹，脂肪組織是能量存儲和動態內分泌器官。尤其是內臟脂肪組織對於調節全身代謝至關重要。例如，在肥胖症患者中VAT功能受損與胰島素抵抗和2型糖尿病相關。表達轉錄因子FOXP3的Treg細胞對於限制免疫應答和抑制組織炎症至關重要，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