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Jill Roberts Center for Inflammatory Bowel Disease

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Microbiota-Induced TNF-like Ligand 1A Drives Group 3 Innate Lymphoid Cell-Mediated Barrier Protection and Intestinal T Cell Activation during Colitis.

TitleMicrobiota-Induced TNF-like Ligand 1A Drives Group 3 Innate Lymphoid Cell-Mediated Barrier Protection and Intestinal T Cell Activation during Colitis.
Publication TypeJournal Article
Year of Publication2018
AuthorsCastellanos JG, Woo V, Viladomiu M, Putzel G, Lima S, Diehl GE, Marderstein AR, Gandara J, Perez AR, Withers DR, Targan SR, Shih DQ, Scherl EJ, Longman RS
JournalImmunity
Volume49
Issue6
Pagination1077-1089.e5
Date Published2018 12 18
ISSN1097-4180
KeywordsAdult, Aged, Animals, Colitis, Female, Humans, Immunity, Innate, Interleukins, Intestinal Mucosa, Lymphocyte Activation, Lymphocytes, Male, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Microbiota, Middle Aged, Phagocytes, T-Lymphocytes, Tumor Necrosis Factor Ligand Superfamily Member 15, Young Adult
Abstract

Inflammatory bowel disease (IBD) results from a dysregulated interaction between the microbiota and a genetically susceptible host. Genetic studies have linked TNFSF15 polymorphisms and its protein TNF-like ligand 1A (TL1A) with IBD, but the functional role of TL1A is not known. Here, we found that adherent IBD-associated microbiota induced TL1A release from CX3CR1 mononuclear phagocytes (MNPs). Using cell-specific genetic deletion models, we identified an essential role for CX3CR1MNP-derived TL1A in driving group 3 innate lymphoid cell (ILC3) production of interleukin-22 and mucosal healing during acute colitis. In contrast to this protective role in acute colitis, TL1A-dependent expression of co-stimulatory molecule OX40L in MHCII ILC3s during colitis led to co-stimulation of antigen-specific T cells that was required for chronic T cell colitis. These results identify a role for ILC3s in activating intestinal T cells and reveal a central role for TL1A in promoting ILC3 barrier immunity during colitis.

DOI10.1016/j.immuni.2018.10.014
Alternate JournalImmunity
PubMed ID30552020
PubMed Central IDPMC6301104
Grant ListR03 DK111852 / DK / NIDDK NIH HHS / United States
K08 DK099381 / DK / NIDDK NIH HHS / United States
UL1 TR002384 / TR / NCATS NIH HHS / United States
R01 AI125264 / AI / NIAID NIH HHS / United States
T32 GM007739 / GM / NIGMS NIH HHS / United States
K08 DK093578 / DK / NIDDK NIH HHS / United States
R01 DK114252 / DK / NIDDK NIH HHS / United States
R01 DK056328 / DK / NIDDK NIH HHS / United States