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Immunity. 2018 Jul 17;49(1):151-163.e5. doi: 10.1016/j.immuni.2018.05.009. Epub 2018 Jul 3.

Critical Role for the Microbiota in CX3CR1+ Intestinal Mononuclear Phagocyte Regulation of Intestinal T Cell Responses.

Author information

1
Alkek Center for Metagenomics and Microbiome Research and the Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
2
The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
3
Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
4
Department of Pediatrics, Section of Diabetes and Endocrinology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA; Biology of Inflammation Center, Baylor College of Medicine, Houston, TX 77030, USA.
5
College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
6
Jill Roberts Center for IBD Research and Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY 10021, USA.
7
The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA; Howard Hughes Medical Institute, New York, NY 10016, USA.
8
Alkek Center for Metagenomics and Microbiome Research and the Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA; Biology of Inflammation Center, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: gdiehl@bcm.edu.

Abstract

The intestinal barrier is vulnerable to damage by microbiota-induced inflammation that is normally restrained through mechanisms promoting homeostasis. Such disruptions contribute to autoimmune and inflammatory diseases including inflammatory bowel disease. We identified a regulatory loop whereby, in the presence of the normal microbiota, intestinal antigen-presenting cells (APCs) expressing the chemokine receptor CX3CR1 reduced expansion of intestinal microbe-specific T helper 1 (Th1) cells and promoted generation of regulatory T cells responsive to food antigens and the microbiota itself. We identified that disruption of the microbiota resulted in CX3CR1+ APC-dependent inflammatory Th1 cell responses with increased pathology after pathogen infection. Colonization with microbes that can adhere to the epithelium was able to compensate for intestinal microbiota loss, indicating that although microbial interactions with the epithelium can be pathogenic, they can also activate homeostatic regulatory mechanisms. Our results identify a cellular mechanism by which the microbiota limits intestinal inflammation and promotes tissue homeostasis.

KEYWORDS:

AIEC E. coli; IL-10; Salmonella; Th1; intestinal immunity; microbiota; mononuclear phagocytes; oral tolerance

PMID:
29980437
PMCID:
PMC6051886
[Available on 2019-07-17]
DOI:
10.1016/j.immuni.2018.05.009

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