title: Interleukin-33 and Interferon-γ Counter-Regulate Group 2 Innate Lymphoid Cell Activation during Immune Perturbation.
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.
authors.affiliation: 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.
authors.forename: Ari B
authors.initials: AB
authors.lastname: Molofsky
authors.affiliation: Diabetes Center, University of California, San Francisco, San Francisco, CA 94143-0795, USA.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Van Gool
authors.affiliation: Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143-0795, USA.
authors.forename: Hong-Erh
authors.initials: HE
authors.lastname: Liang
authors.affiliation: 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.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Van Dyken
authors.affiliation: 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.
authors.forename: Jesse C
authors.initials: JC
authors.lastname: Nussbaum
authors.affiliation: Department of Microbiology & Immunology, University of California, San Francisco, San Francisco, CA 94143-0795, USA.
authors.forename: Jinwoo
authors.initials: J
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Bluestone
authors.affiliation: 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.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Locksley
mesh_terms: D000375:Aging / Q000276:immunology; D000818:Animals; D059305:Diet, High-Fat; D004789:Enzyme Activation / Q000276:immunology; D060889:Inducible T-Cell Co-Stimulator Protein / Q000096:biosynthesis / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology* / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D000067596:Interleukin-33; D007378:Interleukins / Q000276:immunology*; D050152:Intra-Abdominal Fat / Q000166:cytology / Q000276:immunology; D037181:Lectins, C-Type; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology / Q000382:microbiology; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D009559:Nippostrongylus / Q000276:immunology; D009765:Obesity / Q000276:immunology; D011971:Receptors, Immunologic / Q000096:biosynthesis; D017206:Strongylida Infections / Q000276:immunology* / Q000469:parasitology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: C506535:Il33 protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D007376:Interleukin-2; D000067596:Interleukin-33; D007378:Interleukins; C451496:Klrg1 protein, mouse; D037181:Lectins, C-Type; D011971:Receptors, Immunologic; D007371:Interferon-gamma