An IL-9-pulmonary macrophage axis defines the allergic lung inflammatory environment

Despite IL-9 functioning as a pleiotropic cytokine in mucosal environments, the IL-9 responsive cell repertoire is still not well defined. Here, we found IL-9 mediates pro-allergic activities by targeting lung macrophages. IL-9 inhibits alveolar macrophage expansion and promotes recruitment of monocytes that develop into CD11c+/- interstitial macrophage populations. Interstitial macrophages were required for IL-9-dependent allergic responses. Mechanistically, IL-9 affects the function of lung macrophages by inducing Arg1 activity. Compared to Arg1-deficient lung macrophages, Arg1-expressing macrophages co-express greater amounts of CCL5. Adoptive transfer of Arg1+ lung macrophages but not Arg1- lung macrophages can recover allergic inflammation that is lost in Il9r-/- mice. In parallel, the elevated expression of IL-9, IL-9R, Arg1 and CCL5 is correlated with disease in asthma patients. Thus, our study uncovers an IL-9/macrophage/Arg1 axis as a potential therapeutic target for allergic airway inflammation. Overall design: There are two samples, one is pooled cells of WT lung macropahges and WT blood monocytes, the other one is pooled cells of Il9r KO lung macropahges and Il9r KO blood monocytes.