PGI2 controls pulmonary NK cells that prevent airway sensitization to house dust mite allergen

Bryan Simons, Maria E. Ferrini, Sophia Carvalho, David J.P. Bassett, Zeina Jaffar, Kevan Roberts

Research output: Contribution to journalArticlepeer-review

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 PGI2 and its receptor IP during allergic airway sensitization, HDM responses in mice lacking a functional IP receptor (i.e., PGI2 IP receptor-deficient [IP [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 PGI2 in 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.

Original languageEnglish
Pages (from-to)461-471
Number of pages11
JournalJournal of Immunology
Volume198
Issue number1
DOIs
StatePublished - Jan 1 2017

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