Title | Critical Role for the Microbiota in CXCR1 Intestinal Mononuclear Phagocyte Regulation of Intestinal T Cell Responses. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Kim, M, Galan, C, Hill, AA, Wu, W-J, Fehlner-Peach, H, Song, HWon, Schady, D, Bettini, ML, Simpson, KW, Longman, RS, Littman, DR, Diehl, GE |
Journal | Immunity |
Volume | 49 |
Issue | 1 |
Pagination | 151-163.e5 |
Date Published | 2018 Jul 17 |
ISSN | 1097-4180 |
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 CXCR1 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 CXCR1 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. |
DOI | 10.1016/j.immuni.2018.05.009 |
Alternate Journal | Immunity |
PubMed ID | 29980437 |
PubMed Central ID | PMC6051886 |
Grant List | R21 AI123945 / AI / NIAID NIH HHS / United States P30 CA125123 / CA / NCI NIH HHS / United States T32 AI053831 / AI / NIAID NIH HHS / United States P30 DK056338 / DK / NIDDK NIH HHS / United States P30 AI036211 / AI / NIAID NIH HHS / United States S10 RR024574 / RR / NCRR NIH HHS / United States R01 AI125264 / AI / NIAID NIH HHS / United States R01 DK114252 / DK / NIDDK NIH HHS / United States |