Journal of Allergy and Clinical Immunology: Global (Nov 2023)
Eosinophil trafficking in allergen-mediated pulmonary inflammation relies on IL-13–driven CCL-11 and CCL-24 production by tissue fibroblasts and myeloid cells
Abstract
Background: The immunologic mechanisms underlying pulmonary type 2 inflammation, including the dynamics of eosinophil recruitment to the lungs, still need to be elucidated. Objective: We sought to investigate how IL-13–producing TH2 effector cells trigger eosinophil migration in house dust mite (HDM)-driven allergic pulmonary inflammation. Methods: Multiparameter and molecular profiling of murine lungs with HDM-induced allergy was investigated in the absence of IL-13 signaling by using IL-13Rα1–deficient mice and separately through adoptive transfer of CD4+ T cells from IL-5–deficient mice into TCRα–/– mice before allergic inflammation. Results: We demonstrated through single-cell techniques that HDM-driven pulmonary inflammation displays a profile characterized by TH2 effector cell–induced IL-13–dominated eosinophilic inflammation. Using HDM-sensitized IL-13Rα1–/– mice, we found a marked reduction in the influx of eosinophils into the lungs along with a significant downregulation of both CCL-11 and CCL-24. We further found that eosinophil trafficking to the lung relies on production of IL-13–driven CCL-11 and CCL-24 by fibroblasts and Ly6C+ (so-called classical) monocytes. Moreover, this IL-13–mediated eotaxin-dependent eosinophil influx to the lung tissue required IL-5–induced eosinophilia. Finally, we demonstrated that this IL-13–driven eosinophil-dominated pulmonary inflammation was critical for limiting bystander lung transiting Ascaris parasites in a model of allergy and helminth interaction. Conclusion: Our data suggest that IL-5–dependent allergen-specific TH2 effector cell response and subsequent signaling through the IL-13/IL-13Rα1 axis in fibroblasts and myeloid cells regulate the eotaxin-dependent recruitment of eosinophils to the lungs, with multiple downstream consequences, including bystander control of lung transiting parasitic helminths.
