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Nat Immunol. 2016 Dec;17(12):1381-1387. doi: 10.1038/ni.3582. Epub 2016 Oct 17.

A tissue checkpoint regulates type 2 immunity.

Author information

1
Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
2
Department of Laboratory Medicine, University of California, San Francisco, San Francisco, California, USA.
3
Lung Biology Center, University of California, San Francisco, San Francisco, California, USA.
4
Department of Epidemiology and Biostatistics, Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA.
5
Diabetes Center, University of California, San Francisco, San Francisco, California, USA.
6
Innovative Genomics Initiative (IGI), University of California, Berkeley, Berkeley, California, USA.
7
UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
8
Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, California, USA.

Abstract

Group 2 innate lymphoid cells (ILC2s) and CD4+ type 2 helper T cells (TH2 cells) are defined by their similar effector cytokines, which together mediate the features of allergic immunity. We found that tissue ILC2s and TH2 cells differentiated independently but shared overlapping effector function programs that were mediated by exposure to the tissue-derived cytokines interleukin 25 (IL-25), IL-33 and thymic stromal lymphopoietin (TSLP). Loss of these three tissue signals did not affect lymph node priming, but abrogated the terminal differentiation of effector TH2 cells and adaptive lung inflammation in a T cell-intrinsic manner. Our findings suggest a mechanism by which diverse perturbations can activate type 2 immunity and reveal a shared local-tissue-elicited checkpoint that can be exploited to control both innate and adaptive allergic inflammation.

Comment in

PMID:
27749840
PMCID:
PMC5275767
DOI:
10.1038/ni.3582
[Indexed for MEDLINE]
Free PMC Article

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