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Immunity. 2015 Jul 21;43(1):161-74. doi: 10.1016/j.immuni.2015.05.019. Epub 2015 Jun 16.

Interleukin-33 and Interferon-γ Counter-Regulate Group 2 Innate Lymphoid Cell Activation during Immune Perturbation.

Author information

1
Department of Microbiology & Immunology, University of California, San Francisco, San Francisco, CA 94143-0795, USA; Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143-0795, USA.
2
Diabetes Center, University of California, San Francisco, San Francisco, CA 94143-0795, USA.
3
Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143-0795, USA.
4
Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143-0795, USA; Department of Microbiology & Immunology, University of California, San Francisco, San Francisco, CA 94143-0795, USA.
5
Department of Medicine, University of California, San Francisco, San Francisco, CA 94143-0795, USA; Department of Microbiology & Immunology, University of California, San Francisco, San Francisco, CA 94143-0795, USA.
6
Department of Microbiology & Immunology, University of California, San Francisco, San Francisco, CA 94143-0795, USA.
7
Diabetes Center, University of California, San Francisco, San Francisco, CA 94143-0795, USA; Department of Microbiology & Immunology, University of California, San Francisco, San Francisco, CA 94143-0795, USA.
8
Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143-0795, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143-0795, USA; Department of Microbiology & Immunology, University of California, San Francisco, San Francisco, CA 94143-0795, USA. Electronic address: locksley@medicine.ucsf.edu.

Abstract

Group 2 innate lymphoid cells (ILC2s) and regulatory T (Treg) cells are systemically induced by helminth infection but also sustain metabolic homeostasis in adipose tissue and contribute to tissue repair during injury. Here we show that interleukin-33 (IL-33) mediates activation of ILC2s and Treg cells in resting adipose tissue, but also after helminth infection or treatment with IL-2. Unexpectedly, ILC2-intrinsic IL-33 activation was required for Treg cell accumulation in vivo and was independent of ILC2 type 2 cytokines but partially dependent on direct co-stimulatory interactions via ICOSL-ICOS. IFN-γ inhibited ILC2 activation and Treg cell accumulation by IL-33 in infected tissue, as well as adipose tissue, where repression increased with aging and high-fat diet-induced obesity. IL-33 and ILC2s are central mediators of type 2 immune responses that promote tissue and metabolic homeostasis, and IFN-γ suppresses this pathway, likely to promote inflammatory responses and divert metabolic resources necessary to protect the host.

PMID:
26092469
PMCID:
PMC4512852
DOI:
10.1016/j.immuni.2015.05.019
[Indexed for MEDLINE]
Free PMC Article

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