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

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 and Howard L. Weiner
Additional contact information
Thais G. Moreira: Harvard Medical School
Davide Mangani: Harvard Medical School
Laura M. Cox: Harvard Medical School
Jeffrey Leibowitz: Harvard Medical School
Eduardo. L. C. Lobo: Harvard Medical School
Mariana A. Oliveira: Universidade Federal de Minas Gerais
Christian D. Gauthier: Harvard Medical School
Brenda N. Nakagaki: Harvard Medical School
Valerie Willocq: Harvard Medical School
Anya Song: Harvard Medical School
Lydia Guo: Harvard Medical School
David C. A. Lima: Universidade Federal de Minas Gerais
Gopal Murugaiyan: Harvard Medical School
Oleg Butovsky: Harvard Medical School
Galina Gabriely: Harvard Medical School
Ana C. Anderson: Harvard Medical School
Rafael M. Rezende: Harvard Medical School
Ana Maria C. Faria: Universidade Federal de Minas Gerais
Howard L. Weiner: Harvard Medical School

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: 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.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-25115-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25115-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-25115-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().