Year: 2021
Type: article
Abstract: The intestinal mucosa constitutes an environment of closely regulated immune cells. Dendritic cells (DC) interact with the gut microbiome and antigens and are important in maintaining gut homeostasis. Here, we investigate DC transcriptome, phenotype and function in five anatomical locations of the gut lamina propria (LP) which constitute different antigenic environments. We show that DC from distinct gut LP compartments induce distinct T cell differentiation and cytokine secretion. We also find that PD-L1+ DC in the duodenal LP and XCR1+ DC in the colonic LP comprise distinct tolerogenic DC subsets that are crucial for gut homeostasis. Mice lacking PD-L1+ and XCR1+ DC have a proinflammatory gut milieu associated with an increase in Th1/Th17 cells and a decrease in Treg cells and have exacerbated disease in the models of 5-FU-induced mucositis and DSS-induced colitis. Our findings identify PD-L1+ and XCR1+ DC as region-specific physiologic regulators of intestinal homeostasis.
Source: Nature Communications
Authors: Thais G. Moreira, Davide Mangani, Laura M. Cox, Jeffrey Leibowitz, Eduardo. L. C. Lobo, Mariana A. Oliveira, Christian D. Gauthier, Brenda N. Nakagaki, Valerie Willocq, Anya Song, Lydia Guo, David C. A. Lima, Gopal Murugaiyan, Oleg Butovsky, Galina Gabriely, Ana C. Anderson, Rafael M. Rezende, Ana Maria C. Faria, Howard L. Weiner
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,560
Funders: National Science Foundation, Brigham and Women's Hospital, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Universidade Federal de Minas Gerais, RIKEN
OpenAlex ID: W3192158160