PD-L1 + and XCR1 + dendritic cells are region-specific regulators of gut homeostasis.

Autor: Moreira TG; Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. tmoreira@bwh.Harvard.edu., Mangani D; Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Cox LM; Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Leibowitz J; Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Lobo ELC; Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Oliveira MA; Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Gauthier CD; Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Nakagaki BN; Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Willocq V; Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Song A; Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Guo L; Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Lima DCA; Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Murugaiyan G; Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Butovsky O; Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Gabriely G; Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Anderson AC; Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Rezende RM; Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Faria AMC; Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Weiner HL; Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Aug 13; Vol. 12 (1), pp. 4907. Date of Electronic Publication: 2021 Aug 13.
DOI: 10.1038/s41467-021-25115-3
Abstrakt: 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
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