Distinctive CD39CD9 Lung Interstitial Macrophages Suppress IL-23/Th17-mediated Neutrophilic Asthma by Inhibiting NETosis

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Oct 4

PMID 39366998

Authors

Seunghan Han

Bomin Kim

Do Young Hyeon

Daeun Jeong

Jaechan Ryu

Jae-Sung Nam

Yoon Ha Choi

Bo-Ram Kim

Sang Chul Park

Youn Wook Chung

Sung Jae Shin

June-Yong Lee

Jong Kyoung Kim

Jihye Park

Sei Won Lee

Tae-Bum Kim

Jae Hee Cheon

Hyung-Ju Cho

Chang-Hoon Kim

Joo-Heon Yoon

Daehee Hwang

Ji-Hwan Ryu

Affiliations

Soon will be listed here.

Abstract

The IL-23-Th17 axis is responsible for neutrophilic inflammation in various inflammatory diseases. Here, we discover a potential pathway to inhibit neutrophilic asthma. In our neutrophil-dominant asthma (NDA) model, single-cell RNA-seq analysis identifies a subpopulation of CD39CD9 interstitial macrophages (IMs) suppressed by IL-23 in NDA conditions but increased by an IL-23 inhibitor αIL-23p19. Adoptively transferred CD39CD9 IMs suppress neutrophil extracellular trap formation (NETosis), a representative phenotype of NDA, and also Th17 cell activation and neutrophilic inflammation. CD39CD9 IMs first attach to neutrophils in a CD9-dependent manner, and then remove ATP near neutrophils that contribute to NETosis in a CD39-dependent manner. Transcriptomic data from asthmatic patients finally show decreased CD39CD9 IMs in severe asthma than mild/moderate asthma. Our results suggest that CD39CD9 IMs function as a potent negative regulator of neutrophilic inflammation by suppressing NETosis in the IL-23-Th17 axis and can thus serve as a potential therapeutic target for IL-23-Th17-mediated neutrophilic asthma.

Citing Articles

Chronic Inflammation in Asthma: Looking Beyond the Th2 Cell.

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The Importance of Lung Innate Immunity During Health and Disease.

Ryanto G, Suraya R, Nagano T Pathogens. 2025; 14(1).

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