Title: The common γ-chain cytokine IL-7 promotes immunopathogenesis during fungal asthma.
Authors: Reeder, Kristen M; Dunaway, Chad W; Blackburn, Jonathan P; Yu, Zhihong; Matalon, Sadis; Hastie, Annette T; Ampleford, Elizabeth J; Meyers, Deborah A; Steele, Chad
Published In Mucosal Immunol, (2018 09)
Abstract: Asthmatics sensitized to fungi are reported to have more severe asthma, yet the immunopathogenic pathways contributing to this severity have not been identified. In a pilot assessment of human asthmatics, those subjects sensitized to fungi demonstrated elevated levels of the common γ-chain cytokine IL-7 in lung lavage fluid, which negatively correlated with the lung function measurement PC20. Subsequently, we show that IL-7 administration during experimental fungal asthma worsened lung function and increased the levels of type 2 cytokines (IL-4, IL-5, IL-13), proallergic chemokines (CCL17, CCL22) and proinflammatory cytokines (IL-1α, IL-1β). Intriguingly, IL-7 administration also increased IL-22, which we have previously reported to drive immunopathogenic responses in experimental fungal asthma. Employing IL22CreR26ReYFP reporter mice, we identified γδ T cells, iNKT cells, CD4 T cells and ILC3s as sources of IL-22 during fungal asthma; however, only iNKT cells were significantly increased after IL-7 administration. IL-7-induced immunopathogenesis required both type 2 and IL-22 responses. Blockade of IL-7Rα in vivo resulted in attenuated IL-22 production, lower CCL22 levels, decreased iNKT cell, CD4 T-cell and eosinophil recruitment, yet paradoxically increased dynamic lung resistance. Collectively, these results suggest a complex role for IL-7 signaling in allergic fungal asthma.
PubMed ID: 29907867
MeSH Terms: Adult; Asthma/immunology*; Asthma/microbiology*; Bronchoalveolar Lavage Fluid/immunology; Bronchoalveolar Lavage Fluid/microbiology; CD4-Positive T-Lymphocytes/immunology; CD4-Positive T-Lymphocytes/microbiology; Chemokines/immunology; Cytokines/immunology; Female; Fungi/immunology*; Humans; Interleukin-7/immunology*; Lung/immunology; Lung/microbiology; Male; Mycoses/immunology*; Pilot Projects