IL-22 promotes allergic airway inflammation in epicutaneously sensitized mice

Publication date: Available online 18 June 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Juan Manuel Leyva-Castillo, Juhan Yoon, Raif S. Geha
BackgroundSerum IL-22 levels are elevated in atopic dermatitis (AD), which commonly precedes asthma in the atopic march. Epicutaneous (EC) sensitization in mice results in Th2-dominated skin inflammation that mimics AD, and sensitizes the airways for antigen challenge-induced allergic inflammation characterized by the presence of both eosinophils and neutrophils. EC sensitization results in elevated serum levels of IL-22.ObjectiveTo determine the role of IL-22 in antigen-driven airway allergic inflammation following inhalation challenge in EC sensitized mice.MethodsWild type (WT) and Il22^-/- mice were EC sensitized or intraperitoneally (i.p.) immunized with ovalbumin (OVA) and intranasally challenged with antigen. OVA TCR-specific T cells were Th22 polarized in vitro. Airway inflammation, mRNA levels in the lungs and airway hyperresponsiveness (AHR) were examined.ResultsEC sensitization preferentially elicited an IL-22 response compared to i.p. immunization. Intranasal challenge of mice EC-sensitized with OVA elicited in the lungs Il22 mRNA expression, IL-22 production and accumulation of CD3⁺CD4⁺IL22⁺ T cells that co-expressed IL-17A and TNFα. EC-sensitized Il22^-/- mice exhibited diminished eosinophil and neutrophil airway infiltration, and decreased AHR following intranasal OVA challenge. Production of IL-13, IL-17A and TNFα was normal, but IFNγ production was increased in lung cells from airway-challenged EC-sensitized Il22^-/- mice. Intranasal instillation of IFNγ neutralizing antibody partially reversed the defect in eosinophil recruitment. WT recipients of Th22 polarized WT, but not IL-22 deficient, TCR-OVA specific T cells, which both secrete IL-17A and TNFα, developed neutrophil-dominated airway inflammation and AHR upon intranasal OVA challenge. Intranasal instillation of IL-22 with TNFα, but not IL-17A, elicited neutrophil-dominated airway inflammation, and AHR in WT mice, suggesting that the loss of IL-22 synergy with TNFα contributed to the defective recruitment of neutrophils into the airways of Il22^-/- mice. TNFα, but not IL-22 blockade at the time of antigen inhalation challenge inhibited airway inflammation in EC sensitized miceConclusionEC sensitization promotes the generation of antigen-specific IL-22 producing T cells that promote airway inflammation and AHR following antigen challenge, suggesting that IL-22 plays an important role in the atopic march.

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IL-22 plays an important role in the atopic march


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