小柯机器人

加拿大多伦多大学Daniel J. Drucker团队近期取得了重要工作进展，他们报道了肠道上皮内淋巴细胞GLP-1R在控制代谢、微生物群和T细胞诱导的炎症中的不同作用。相关论文2022年8月25日在线发表于《细胞—代谢》杂志上。

肠道上皮内淋巴细胞(IEL)被认为可以校准胰高血糖素样肽1（GLP-1）的生物利用度，从而调节全身葡萄糖和脂质代谢。研究人员表明肠道IEL GLP-1受体（GLP-1R）不是肠内分泌L细胞GLP-1分泌和葡萄糖稳态所必需的，也不是GLP-1R激动剂（GLP-1Ras）的代谢益处所必需的。相反，肠道IEL GLP-1R对于GLP-1RA对肠道微生物群的全面影响至关重要。

此外，与血糖控制或体重减轻无关，GLP-1RAs的抗炎作用需要肠道IEL GLP-1R选择性抑制局部和全身T细胞诱导的炎症，而不是脂多糖诱导的炎症。这种效应是通过抑制肠道IEL效应器功能介导的，该功能与以蛋白激酶A依赖性方式抑制近端T细胞受体信号传导有关。这些数据重新定位了L细胞-肠道IEL GLP-1R轴的关键作用，揭示了将肠道IELs中GLP-1R激活与调节微生物群组成以及控制肠道和全身炎症联系起来的机制。

附：英文原文

Title: Divergent roles for the gut intraepithelial lymphocyte GLP-1R in control of metabolism, microbiota, and T cell-induced inflammation

Author: Chi Kin Wong, Bernardo Yusta, Jacqueline A. Koehler, Laurie L. Baggio, Brent A. McLean, Dianne Matthews, Randy J. Seeley, Daniel J. Drucker

Issue&Volume: 2022-08-25

Abstract: Gut intraepithelial lymphocytes (IELs) are thought to calibrate glucagon-like peptide1 (GLP-1) bioavailability, thereby regulating systemic glucose and lipid metabolism.Here, we show that the gut IEL GLP-1 receptor (GLP-1R) is not required for enteroendocrineL cell GLP-1 secretion and glucose homeostasis nor for the metabolic benefits of GLP-1Ragonists (GLP-1RAs). Instead, the gut IEL GLP-1R is essential for the full effectsof GLP-1RAs on gut microbiota. Moreover, independent of glucose control or weightloss, the anti-inflammatory actions of GLP-1RAs require the gut IEL GLP-1R to selectivelyrestrain local and systemic T cell-induced, but not lipopolysaccharide-induced, inflammation.Such effects are mediated by the suppression of gut IEL effector functions linkedto the dampening of proximal T cell receptor signaling in a protein-kinase-A-dependentmanner. These data reposition key roles of the L cell-gut IEL GLP-1R axis, revealingmechanisms linking GLP-1R activation in gut IELs to modulation of microbiota compositionand control of intestinal and systemic inflammation.

DOI: 10.1016/j.cmet.2022.08.003

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00346-1

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