Myeloid-IL4Rα is an indispensable link in IL-33-ILCs-IL-13-IL4Rα axis of eosinophil recruitment in murine lungs

Increased eosinophil recruitment is a hallmark feature of eosinophilic disorders. Here, we delineated the key molecular and cellular players involved in physiological eosinophilic recruitment during normal postnatal lung development in mice. Physiological eosinophilic recruitment was consistently present in 7-, 10-, and 15-day-old neonatal mice, but not in 42-day-old mice. This feature was completely abolished in interleukin 33 (IL-33)-, interleukin 2 receptor gamma chain (IL2r gamma)-, and interleukin 4 receptor alpha (IL4R alpha)-knockout mice, but not in recombination activating gene 1 (Rag1)-knockout mice demonstrating an indispensable role for IL-33, innate lymphoid cells (ILCs), and IL4R alpha in eosinophil recruitment. Interestingly, myeloid-specific IL4R alpha -deficient (mye-IL4R alpha (-/-)) mice had significantly reduced eosinophilia in the airspaces that was associated with reduced levels of IL-4 and IL-5 in the bronchoalveolar lavage fluid (BALF). Further, we tested the effect of myeloid-specific IL4R alpha deficiency on IL-13-induced eosinophil recruitment into adult lung airspaces. Eosinophil recruitment into the airspaces was elevated in IL-13-treated WT mice but not in IL-13-treated mye-IL4R alpha (-/-) mice. Consistent with the degree of eosinophilia, the BALF levels of eosinophil recruitment-associated cytokines were significantly elevated in IL-13-treated WT but not in IL-13-treated mye-IL4R alpha (-/-) mice. These data establish that myeloid-IL4R alpha is an indispensable component of the IL-33-ILCsIL-13-IL4R alpha axis of eosinophil recruitment.

Automated summary

Research has shown that IL-33, ILCs, and IL4R alpha play important roles in the recruitment of eosinophils during normal postnatal lung development in mice. Myeloid-specific IL4R alpha deficiency results in reduced eosinophil numbers in the airspaces and decreased levels of related cytokines.