A binary module for microbiota-mediated regulation of γδ17 cells, hallmarked by microbiota-driven expression of programmed cell death protein 1

Hsin I. Huang, Yue Xue, Mark L. Jewell, Chin Yee Tan, Barbara Theriot, Nupur Aggarwal, Jacob Dockterman, Yang Ding Lin, Erin A. Schroeder, Donghai Wang, Na Xiong, Jörn Coers, Mari L. Shinohara, Neeraj K. Surana, Gianna Elena Hammer

Producción científica: Articlerevisión exhaustiva

Resumen

Little is known about how microbiota regulate innate-like γδ T cells or how these restrict their effector functions within mucosal barriers, where microbiota provide chronic stimulation. Here, we show that microbiota-mediated regulation of γδ17 cells is binary, where microbiota instruct in situ interleukin-17 (IL-17) production and concomitant expression of the inhibitory receptor programmed cell death protein 1 (PD-1). Microbiota-driven expression of PD-1 and IL-17 and preferential adoption of a PD-1high phenotype are conserved for γδ17 cells across multiple mucosal barriers. Importantly, microbiota-driven PD-1 inhibits in situ IL-17 production by mucosa-resident γδ17 effectors, linking microbiota to their simultaneous activation and suppression. We further show the dynamic nature of this microbiota-driven module and define an inflammation-associated activation state for γδ17 cells marked by augmented PD-1, IL-17, and lipid uptake, thus linking the microbiota to dynamic subset-specific activation and metabolic remodeling to support γδ17 effector functions in a microbiota-dense tissue environment.

Idioma originalEnglish (US)
Número de artículo112951
PublicaciónCell Reports
Volumen42
N.º8
DOI
EstadoPublished - ago 29 2023

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

Huella

Profundice en los temas de investigación de 'A binary module for microbiota-mediated regulation of γδ17 cells, hallmarked by microbiota-driven expression of programmed cell death protein 1'. En conjunto forman una huella única.

Citar esto