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诱导产生的人调节性 T 细胞表达胰高血糖素样肽-1 受体。

Induced Human Regulatory T Cells Express the Glucagon-like Peptide-1 Receptor.

机构信息

The LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.

Grünenthal GmbH, Zieglerstr. 6, 52078 Aachen, Germany.

出版信息

Cells. 2022 Aug 19;11(16):2587. doi: 10.3390/cells11162587.

DOI:10.3390/cells11162587
PMID:36010663
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9406769/
Abstract

The glucagon-like peptide-1 receptor (GLP-1R) plays a key role in metabolism and is an important therapeutic target in diabetes and obesity. Recent studies in experimental animals have shown that certain subsets of T cells express functional GLP-1R, indicating an immune regulatory role of GLP-1. In contrast, less is known about the expression and function of the GLP-1R in human T cells. Here, we provide evidence that activated human T cells express GLP-1R. The expressed GLP-1R was functional, as stimulation with a GLP-1R agonist triggered an increase in intracellular cAMP, which was abrogated by a GLP-1R antagonist. Analysis of CD4 T cells activated under T helper (Th) 1, Th2, Th17 and regulatory T (Treg) cell differentiation conditions indicated that GLP-1R expression was most pronounced in induced Treg (iTreg) cells. Through multimodal single-cell CITE- and TCR-sequencing, we detected GLP-1R expression in 29-34% of the FoxP3CD25CD127 iTreg cells. GLP-1R cells showed no difference in their TCR-gene usage nor CDR3 lengths. Finally, we demonstrated the presence of GLP-1RCD4 T cells in skin from patients with allergic contact dermatitis. Taken together, the present data demonstrate that T cell activation triggers the expression of functional GLP-1R in human CD4 T cells. Given the high induction of GLP-1R in human iTreg cells, we hypothesize that GLP-1R iTreg cells play a key role in the anti-inflammatory effects ascribed to GLP-1R agonists in humans.

摘要

胰高血糖素样肽-1 受体 (GLP-1R) 在代谢中发挥关键作用，是糖尿病和肥胖症的重要治疗靶点。最近在实验动物中的研究表明，某些 T 细胞亚群表达功能性 GLP-1R，表明 GLP-1 具有免疫调节作用。相比之下，人们对人类 T 细胞中 GLP-1R 的表达和功能知之甚少。在这里，我们提供了激活的人类 T 细胞表达 GLP-1R 的证据。表达的 GLP-1R 是功能性的，因为 GLP-1R 激动剂的刺激会引发细胞内 cAMP 的增加，而 GLP-1R 拮抗剂则会阻断这种增加。对在辅助性 T 细胞 (Th) 1、Th2、Th17 和调节性 T (Treg) 细胞分化条件下激活的 CD4 T 细胞进行分析表明，GLP-1R 的表达在诱导的 Treg (iTreg) 细胞中最为明显。通过多模态单细胞 CITE-和 TCR 测序，我们在 29-34%的 FoxP3CD25CD127 iTreg 细胞中检测到 GLP-1R 的表达。GLP-1R 细胞在 TCR 基因使用或 CDR3 长度上没有差异。最后，我们证明了过敏接触性皮炎患者皮肤中存在 GLP-1RCD4 T 细胞。总之，本研究数据表明，T 细胞激活会触发人类 CD4 T 细胞表达功能性 GLP-1R。鉴于人类 iTreg 细胞中 GLP-1R 的高诱导，我们假设 GLP-1R iTreg 细胞在归因于 GLP-1R 激动剂的人类中发挥抗炎作用中发挥关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bbf/9406769/61af37c2de00/cells-11-02587-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bbf/9406769/d3e5d7d1545c/cells-11-02587-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bbf/9406769/0a9083145d42/cells-11-02587-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bbf/9406769/47ff64ae0066/cells-11-02587-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bbf/9406769/fa005e728a8f/cells-11-02587-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bbf/9406769/2187f93c8dfe/cells-11-02587-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bbf/9406769/61af37c2de00/cells-11-02587-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bbf/9406769/d3e5d7d1545c/cells-11-02587-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bbf/9406769/0a9083145d42/cells-11-02587-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bbf/9406769/47ff64ae0066/cells-11-02587-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bbf/9406769/fa005e728a8f/cells-11-02587-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bbf/9406769/2187f93c8dfe/cells-11-02587-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bbf/9406769/61af37c2de00/cells-11-02587-g006.jpg

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