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

Yongyao FuJocelyn WangBaohua ZhouAbigail PajulasHongyu GaoBaskar RamdasByung-Hee KohBenjamin J UlrichShuangshuang YangReuben KapurJean-Christophe RenauldSophie PaczesnyYunlong LiuRobert M TighePaula Licona-LimónRichard A FlavellShogo TakatsukaDaisuke KitamuraRobert S TepperJie SunMark H Kaplan
Published in: Science immunology (2022)
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.
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