LATE-BREAKING ABSTRACT: Identification of a novel lung-resident eosinophil population with immunomodulatory properties in mice

Introduction: As opposed to their well-characterized contributions to inflammatory processes, tissue eosinophils are now also thought to contribute to immune homeostasis at mucosal sites such as the gut. Yet, whether such steady-state eosinophils exist in the lung is currently unclear. Methods: We combined flow cytometry phenotyping and sorting, immuno-histochemistry, microscopy and microarray analyses to identify and characterize lung eosinophil populations in naive versus host dust mite (HDM)-treated mice. We then used eosinophil-deficient transgenic mice as well as models of allergic airway sensitization to assess their functions. Results: In the lung of naive and HDM-treated mice, we identified resident eosinophils (rEOS) as eosinophilic cells with a distinct phenotype surface (SiglecF + CD125 int ), morphology (donut shape nucleus), localization (in parenchyma) and transcriptional signature than lung inflammatory eosinophils (iEOS) found in HDM-treated mice (SiglecF high CD125 int cells, polylobuled nucleus, around bronchi). We showed that mice deficient for eosinophils (ΔdblGATA mice) are deficient in rEos and are more sensitive to HDM-induced allergic airway sensitization than control mice, suggesting a role for rEOS in inhibiting allergen-induced sensitization. Moreover, dendritic cell(DC)-rEos co-culture models suggest that rEos may act directly on DCs to prevent development of airway allergy. Conclusion: We report on a previously unknown mouse lung-rEOS population which is distinct from lung iEOS and exhibit negative immunoregulatory roles according to experimental data from mouse models. We are now investigating the potential presence of such rEos in the human lung.