The common γ-chain cytokine IL-7 promotes immunopathogenesis during fungal asthma

Kristen M. Reeder, Chad W. Dunaway, Jonathan P. Blackburn, Zhihong Yu, Sadis Matalon, Annette T. Hastie, Elizabeth J. Ampleford, Deborah A. Meyers, Chad Steele

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1352-1362
Number of pages11
JournalMucosal Immunology
Volume11
Issue number5
DOIs
StatePublished - Sep 1 2018
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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