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

Yongyao Fu, Jocelyn Wang, Baohua Zhou, Abigail Pajulas, Hongyu Gao, Baskar Ramdas, Byunghee Koh, Benjamin J. Ulrich, Shuangshuang Yang, Reuben Kapur, Jean Christophe Renauld, Sophie Paczesny, Yunlong Liu, Robert M. Tighe, Paula Licona-Limón, Richard A. Flavell, Shogo Takatsuka, Daisuke Kitamura, Robert S. Tepper, Jie SunMark H. Kaplan

Research output: Contribution to journalArticlepeer-review

Abstract

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 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.

Original languageEnglish
Article numbereabi9768
JournalScience immunology
Volume7
Issue number68
DOIs
Publication statusPublished - Feb 2022

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