Eosinophil trafficking in allergen-mediated pulmonary inflammation relies on IL-13-driven CCL-11 and CCL-24 production by tissue fibroblasts and myeloid cells.

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 T2 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 T2 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 parasites in a model of allergy and helminth interaction.

CONCLUSION

Our data suggest that IL-5-dependent allergen-specific T2 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.