Elsevier

Mucosal Immunology

Volume 7, Issue 4, July 2014, Pages 958-968
Mucosal Immunology

Article
The TNF-family cytokine TL1A promotes allergic immunopathology through group 2 innate lymphoid cells

https://doi.org/10.1038/mi.2013.114Get rights and content
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Abstract

The tumor necrosis factor (TNF)-family cytokine TL1A (TNFSF15) costimulates T cells and promotes diverse T cell-dependent models of autoimmune disease through its receptor DR3. TL1A polymorphisms also confer susceptibility to inflammatory bowel disease. Here, we find that allergic pathology driven by constitutive TL1A expression depends on interleukin-13 (IL-13), but not on T, NKT, mast cells, or commensal intestinal flora. Group 2 innate lymphoid cells (ILC2) express surface DR3 and produce IL-13 and other type 2 cytokines in response to TL1A. DR3 is required for ILC2 expansion and function in the setting of T cell-dependent and -independent models of allergic disease. By contrast, DR3-deficient ILC2 can still differentiate, expand, and produce IL-13 when stimulated by IL-25 or IL-33, and mediate expulsion of intestinal helminths. These data identify costimulation of ILC2 as a novel function of TL1A important for allergic lung disease, and suggest that TL1A may be a therapeutic target in these settings.

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Published online: 25 December 2013

SUPPLEMENTARY MATERIAL is linked to the online version of the paper

Supplementary information The online version of this article (doi:10.1038/mi.2013.114) contains supplementary material, which is available to authorized users.