Format

Send to

Choose Destination
Immunity. 2018 Jun 19;48(6):1195-1207.e6. doi: 10.1016/j.immuni.2018.05.003. Epub 2018 Jun 12.

Tissue-Restricted Adaptive Type 2 Immunity Is Orchestrated by Expression of the Costimulatory Molecule OX40L on Group 2 Innate Lymphoid Cells.

Author information

1
MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK; University of Cambridge, CRUK Cambridge Institute, Cambridge CB2 0RE, UK. Electronic address: tim.halim@cruk.cam.ac.uk.
2
MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
3
MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK; Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
4
University of Cambridge, CRUK Cambridge Institute, Cambridge CB2 0RE, UK.
5
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton CB10 1SA, UK.
6
Division of Cellular Immunology, German Cancer Research Center, Heidelberg 69120, Germany.
7
Imperial College London, Department of Medicine, London, UK.
8
King's College London, Department of Medical and Molecular Genetics, London, UK.
9
Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland.
10
University of Birmingham, Institute of Immunology and Immunotherapy, Birmingham B15 2TT, UK.
11
MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. Electronic address: anm@mrc-lmb.cam.ac.uk.

Abstract

The local regulation of type 2 immunity relies on dialog between the epithelium and the innate and adaptive immune cells. Here we found that alarmin-induced expression of the co-stimulatory molecule OX40L on group 2 innate lymphoid cells (ILC2s) provided tissue-restricted T cell co-stimulation that was indispensable for Th2 and regulatory T (Treg) cell responses in the lung and adipose tissue. Interleukin (IL)-33 administration resulted in organ-specific surface expression of OX40L on ILC2s and the concomitant expansion of Th2 and Treg cells, which was abolished upon deletion of OX40L on ILC2s (Il7raCre/+Tnfsf4fl/fl mice). Moreover, Il7raCre/+Tnfsf4fl/fl mice failed to mount effective Th2 and Treg cell responses and corresponding adaptive type 2 pulmonary inflammation arising from Nippostrongylus brasiliensis infection or allergen exposure. Thus, the increased expression of OX40L in response to IL-33 acts as a licensing signal in the orchestration of tissue-specific adaptive type 2 immunity, without which this response fails to establish.

KEYWORDS:

IL-33; ILC2; OX40L; Th2 cells; Treg cells; allergy; helminth; type 2 immunity

PMID:
29907525
PMCID:
PMC6015114
DOI:
10.1016/j.immuni.2018.05.003
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center