Format

Send to

Choose Destination
Immunity. 2018 Dec 18;49(6):1077-1089.e5. doi: 10.1016/j.immuni.2018.10.014. Epub 2018 Dec 11.

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

Author information

1
Jill Roberts Institute for Research in IBD, Weill Cornell Medicine, New York, NY, 10021, USA.
2
Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, TX, 77030, USA.
3
Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
4
F. Widjaja Foundation, Inflammatory Bowel and Immunology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA.
5
Jill Roberts Center for IBD, Weill Cornell Medicine, New York, NY, 10021, USA.
6
Jill Roberts Institute for Research in IBD, Weill Cornell Medicine, New York, NY, 10021, USA; Jill Roberts Center for IBD, Weill Cornell Medicine, New York, NY, 10021, USA. Electronic address: ral2006@med.cornell.edu.

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 CX3CR1+MNP-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.

KEYWORDS:

CX(3)CR1(+) mononuclear phagocytes; Crohn’s disease; Inflammatory bowel disease; TL1A; innate lymphoid cell

PMID:
30552020
PMCID:
PMC6301104
[Available on 2019-12-18]
DOI:
10.1016/j.immuni.2018.10.014

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center