An IL-9-pulmonary Macrophage Axis Defines the Allergic Lung Inflammatory Environment

Overview

Journal Sci Immunol

Specialty Allergy & Immunology

Date 2022 Feb 18

PMID 35179949

Authors

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-Limon

Richard A Flavell

Shogo Takatsuka

Daisuke Kitamura

Robert S Tepper

Jie Sun

Mark H Kaplan

Affiliations

Soon will be listed here.

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 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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