title: PGI2 Controls Pulmonary NK Cells That Prevent Airway Sensitization to House Dust Mite Allergen.
abstract: In allergic asthma, inhalation of airborne allergens such as the house dust mite (HDM) effectively activates both innate and adaptive immunity in the lung mucosa. To determine the role of the eicosanoid PGI2and its receptor IP during allergic airway sensitization, HDM responses in mice lacking a functional IP receptor (i.e., PGI2IP receptor-deficient [IP-/-]) were compared with wild type (WT) mice. Surprisingly, IP-/-mice had increased numbers of pulmonary CD3-NK1.1+Ly49b+NK cells producing IFN-γ that was inversely associated with the number of type 2 innate lymphoid cells (ILC2s) expressing IL-33Rα and IL-13 compared with WT animals. This phenomenon was associated with elevated CX3CL1 levels in the airways of IP-/-mice and treatment with a neutralizing Ab to CX3CL1 reduced IFN-γ production by the lung NK cells. Remarkably, IP-/-mice were less responsive to HDM challenge than WT counterparts because intranasal instillation of the allergen induced markedly reduced levels of airway eosinophils, CD4+lymphocyte infiltration, and mucus production, as well as depressed levels of CCL2 chemokine and Th2 cytokines. NK cells were responsible for such attenuated responses because depletion of NK1.1+cells in IP-/-mice restored both the HDM-induced lung inflammation and ILC2 numbers, whereas transfer of CD3-NK1.1+NK cells into the airways of WT hosts suppressed the inflammatory response. Collectively, these data demonstrate a hitherto unknown role for PGI2in regulating the number and properties of NK cells resident in lung tissue and reveal a role for NK cells in limiting lung tissue ILC2s and preventing allergic inflammatory responses to inhaled HDM allergen.
authors.affiliation: Center for Environmental Health Sciences, Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT 59812; and.
authors.forename: Bryan
authors.initials: B
authors.lastname: Simons
authors.affiliation: Center for Environmental Health Sciences, Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT 59812; and.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Ferrini
authors.affiliation: Center for Environmental Health Sciences, Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT 59812; and.
authors.forename: Sophia
authors.initials: S
authors.lastname: Carvalho
authors.affiliation: Department of Family Medicine and Public Health Sciences, School of Medicine, Wayne State University, Detroit, MI 48201.
authors.forename: David J P
authors.initials: DJ
authors.lastname: Bassett
authors.affiliation: Center for Environmental Health Sciences, Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT 59812; and kevan.roberts@umontana.edu zeina.jaffar@umontana.edu.
authors.forename: Zeina
authors.initials: Z
authors.lastname: Jaffar
authors.affiliation: Center for Environmental Health Sciences, Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT 59812; and kevan.roberts@umontana.edu zeina.jaffar@umontana.edu.
authors.forename: Kevan
authors.initials: K
authors.lastname: Roberts
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology*; D004195:Disease Models, Animal; D011464:Epoprostenol / Q000276:immunology*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007694:Killer Cells, Natural / Q000276:immunology*; D008168:Lung / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039981:Pyroglyphidae / Q000276:immunology; D044006:Receptors, Epoprostenol / Q000276:immunology*; D012130:Respiratory Hypersensitivity / Q000276:immunology*
chemical_list: D039741:Antigens, Dermatophagoides; D044006:Receptors, Epoprostenol; D011464:Epoprostenol