| Autor: |
Chi Kin, Wong, Bernardo, Yusta, Jacqueline A, Koehler, Laurie L, Baggio, Brent A, McLean, Dianne, Matthews, Randy J, Seeley, Daniel J, Drucker |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Cell Metabolism. 34:1514-1531.e7 |
| ISSN: |
1550-4131 |
| Popis: |
Gut intraepithelial lymphocytes (IELs) are thought to calibrate glucagon-like peptide 1 (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 enteroendocrine L cell GLP-1 secretion and glucose homeostasis nor for the metabolic benefits of GLP-1R agonists (GLP-1RAs). Instead, the gut IEL GLP-1R is essential for the full effects of GLP-1RAs on gut microbiota. Moreover, independent of glucose control or weight loss, the anti-inflammatory actions of GLP-1RAs require the gut IEL GLP-1R to selectively restrain local and systemic T cell-induced, but not lipopolysaccharide-induced, inflammation. Such effects are mediated by the suppression of gut IEL effector functions linked to the dampening of proximal T cell receptor signaling in a protein-kinase-A-dependent manner. These data reposition key roles of the L cell-gut IEL GLP-1R axis, revealing mechanisms linking GLP-1R activation in gut IELs to modulation of microbiota composition and control of intestinal and systemic inflammation. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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