Fu, YongyaoWang, JocelynZhou, BaohuaPajulas, AbigailGao, HongyuRamdas, BaskarKoh, ByungheeUlrich, Benjamin J.Yang, ShuangshuangKapur, ReubenRenauld, Jean-ChristophePaczesny, SophieLiu, YunlongTighe, Robert M.Licona-Limón, PaulaFlavell, Richard A.Takatsuka, ShogoKitamura, DaisukeTepper, Robert S.Sun, JieKaplan, Mark H.2023-08-022023-08-022022Fu Y, Wang J, Zhou B, et al. An IL-9-pulmonary macrophage axis defines the allergic lung inflammatory environment. Sci Immunol. 2022;7(68):eabi9768. doi:10.1126/sciimmunol.abi9768https://hdl.handle.net/1805/34699Despite IL-9 functioning as a pleiotropic cytokine in mucosal environments, the IL-9-responsive cell repertoire is still not well defined. Here, we found that IL-9 mediates proallergic activities in the lungs by targeting lung macrophages. IL-9 inhibits alveolar macrophage expansion and promotes recruitment of monocytes that develop into CD11c+ and CD11c- interstitial macrophage populations. Interstitial macrophages were required for IL-9-dependent allergic responses. Mechanistically, IL-9 affected the function of lung macrophages by inducing Arg1 activity. Compared with Arg1-deficient lung macrophages, Arg1-expressing macrophages expressed greater amounts of CCL5. Adoptive transfer of Arg1+ lung macrophages but not Arg1- lung macrophages promoted allergic inflammation that Il9r-/- mice were protected against. In parallel, the elevated expression of IL-9, IL-9R, Arg1, and CCL5 was correlated with disease in patients with asthma. Thus, our study uncovers an IL-9/macrophage/Arg1 axis as a potential therapeutic target for allergic airway inflammation.en-USPublisher PolicyAllergensDermatophagoides antigensAsthmaInflammationInterleukin-9Article