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Divergent roles for the gut intraepithelial lymphocyte GLP-1R in control of metabolism, microbiota, and T cell-induced inflammation.
Wong, Chi Kin; Yusta, Bernardo; Koehler, Jacqueline A; Baggio, Laurie L; McLean, Brent A; Matthews, Dianne; Seeley, Randy J; Drucker, Daniel J.
Afiliación
  • Wong CK; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.
  • Yusta B; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.
  • Koehler JA; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.
  • Baggio LL; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.
  • McLean BA; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.
  • Matthews D; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.
  • Seeley RJ; Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
  • Drucker DJ; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada. Electronic address: drucker@lunenfeld.ca.
Cell Metab ; 34(10): 1514-1531.e7, 2022 10 04.
Article en En | MEDLINE | ID: mdl-36027914
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Microbioma Gastrointestinal / Linfocitos Intraepiteliales Límite: Humans Idioma: En Revista: Cell Metab Asunto de la revista: METABOLISMO Año: 2022 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Microbioma Gastrointestinal / Linfocitos Intraepiteliales Límite: Humans Idioma: En Revista: Cell Metab Asunto de la revista: METABOLISMO Año: 2022 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos