LAG3 Regulatory T Cells Restrain Interleukin-23-Producing CX3CR1 Gut-Resident Macrophages during Group 3 Innate Lymphoid Cell-Driven Colitis.

Bauché, David; Joyce-Shaikh, Barbara; Jain, Renu; Grein, Jeff; Ku, Karin S; Blumenschein, Wendy M; Ganal-Vonarburg, Stephanie C.; Wilson, Douglas C; McClanahan, Terrill K; Malefyt, Rene de Waal; Macpherson, Andrew J.; Annamalai, Lakshmanan; Yearley, Jennifer H; Cua, Daniel J (2018). LAG3 Regulatory T Cells Restrain Interleukin-23-Producing CX3CR1 Gut-Resident Macrophages during Group 3 Innate Lymphoid Cell-Driven Colitis. Immunity, 49(2), 342-352.e5. Cell Press 10.1016/j.immuni.2018.07.007

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Interleukin-22 (IL-22)-producing group 3 innate lymphoid cells (ILC3) maintains gut homeostasis but can also promote inflammatory bowel disease (IBD). The regulation of ILC3-dependent colitis remains to be elucidated. Here we show that Foxp3 regulatory T cells (Treg cells) prevented ILC3-mediated colitis in an IL-10-independent manner. Treg cells inhibited IL-23 and IL-1β production from intestinal-resident CX3CR1 macrophages but not CD103 dendritic cells. Moreover, Treg cells restrained ILC3 production of IL-22 through suppression of CX3CR1 macrophage production of IL-23 and IL-1β. This suppression was contact dependent and was mediated by latent activation gene-3 (LAG-3)-an immune checkpoint receptor-expressed on Treg cells. Engagement of LAG-3 on MHC class II drove profound immunosuppression of CX3CR1 tissue-resident macrophages. Our study reveals that the health of the intestinal mucosa is maintained by an axis driven by Treg cells communication with resident macrophages that withhold inflammatory stimuli required for ILC3 function.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Gastroenterology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie

UniBE Contributor:

Ganal-Vonarburg, Stephanie and Macpherson, Andrew

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1074-7613

Publisher:

Cell Press

Language:

English

Submitter:

Thi Thao Anh Pham

Date Deposited:

09 Jan 2019 09:37

Last Modified:

09 Jan 2019 09:37

Publisher DOI:

10.1016/j.immuni.2018.07.007

PubMed ID:

30097293

BORIS DOI:

10.7892/boris.122379

URI:

https://boris.unibe.ch/id/eprint/122379

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