title: Cutting edge: maresin-1 engages regulatory T cells to limit type 2 innate lymphoid cell activation and promote resolution of lung inflammation.
abstract: Asthma is a chronic inflammatory disease that fails to resolve. Recently, a key role for type 2 innate lymphoid cells (ILC2s) was linked to asthma pathogenesis; however, mechanisms for ILC2 regulation remain to be determined. In this study, metabololipidomics of murine lungs identified temporal changes in endogenous maresin 1 (MaR1) during self-limited allergic inflammation. Exogenous MaR1 reduced lung inflammation and ILC2 expression of IL-5 and IL-13 and increased amphiregulin. MaR1 augmented de novo generation of regulatory T cells (Tregs), which interacted with ILC2s to markedly suppress cytokine production in a TGF-β-dependent manner. Ab-mediated depletion of Tregs interrupted MaR1 control of ILC2 expression of IL-13 in vivo. Together, the findings uncover Tregs as potent regulators of ILC2 activation; MaR1 targets Tregs and ILC2s to restrain allergic lung inflammation, suggesting MaR1 as the basis for a new proresolving therapeutic approach to asthma and other chronic inflammatory diseases.
authors.affiliation: Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
authors.forename: Nandini
authors.initials: N
authors.lastname: Krishnamoorthy
authors.affiliation: Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Burkett
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
authors.forename: Jesmond
authors.initials: J
authors.lastname: Dalli
authors.affiliation: Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
authors.forename: Raja-Elie E
authors.initials: RE
authors.lastname: Abdulnour
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
authors.forename: Romain
authors.initials: R
authors.lastname: Colas
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY 14642; and.
authors.forename: Sesquile
authors.initials: S
authors.lastname: Ramon
authors.affiliation: Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY 14642; and.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Phipps
authors.affiliation: Department of Chemistry, University of Southern California, Los Angeles, CA 90089.
authors.forename: Nicos A
authors.initials: NA
authors.lastname: Petasis
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Kuchroo
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
authors.forename: Charles N
authors.initials: CN
authors.lastname: Serhan
authors.affiliation: Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; blevy@partners.org.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Levy
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism; D007113:Immunity, Innate; D056747:Immunomodulation; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D011014:Pneumonia / Q000276:immunology* / Q000378:metabolism* / Q000628:therapy; D016176:T-Lymphocyte Subsets; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*
chemical_list: C535211:7,14-dihydroxydocosa-4,8,10,12,16,19-hexaenoic acid; D016207:Cytokines; D004281:Docosahexaenoic Acids