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白细胞介素-9 促进过敏性气道炎症中的肥大细胞祖细胞增殖和 CCR2 依赖性肥大细胞迁移。

Interleukin-9 promotes mast cell progenitor proliferation and CCR2-dependent mast cell migration in allergic airway inflammation.

机构信息

Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, USA.

Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, USA.

出版信息

Mucosal Immunol. 2023 Aug;16(4):432-445. doi: 10.1016/j.mucimm.2023.05.002. Epub 2023 May 11.

DOI:10.1016/j.mucimm.2023.05.002
PMID:37172907
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10482122/
Abstract

Allergic asthma is a chronic lung disease characterized by airway hyperresponsiveness and cellular infiltration that is exacerbated by immunoglobulin E-dependent mast cell (MC) activation. Interleukin-9 (IL-9) promotes MC expansion during allergic inflammation but precisely how IL-9 expands tissue MCs and promotes MC function is unclear. In this report, using multiple models of allergic airway inflammation, we show that both mature MCs (mMCs) and MC progenitors (MCp) express IL-9R and respond to IL-9 during allergic inflammation. IL-9 acts on MCp in the bone marrow and lungs to enhance proliferative capacity. Furthermore, IL-9 in the lung stimulates the mobilization of CCR2+ mMC from the bone marrow and recruitment to the allergic lung. Mixed bone marrow chimeras demonstrate that these are intrinsic effects in the MCp and mMC populations. IL-9-producing T cells are both necessary and sufficient to increase MC numbers in the lung in the context of allergic inflammation. Importantly, T cell IL-9-mediated MC expansion is required for the development of antigen-induced and MC-dependent airway hyperreactivity. Collectively, these data demonstrate that T cell IL-9 induces lung MC expansion and migration by direct effects on the proliferation of MCp and the migration of mMC to mediate airway hyperreactivity.

摘要

过敏性哮喘是一种慢性肺部疾病，其特征是气道高反应性和细胞浸润，这种反应会因免疫球蛋白 E 依赖性肥大细胞 (MC) 激活而加剧。白细胞介素-9 (IL-9) 在过敏炎症期间促进 MC 扩增，但 IL-9 如何扩增组织 MC 并促进 MC 功能尚不清楚。在本报告中，我们使用多种过敏性气道炎症模型，表明成熟 MC (mMC) 和 MC 祖细胞 (MCp) 均表达 IL-9R，并在过敏炎症期间对 IL-9 作出反应。IL-9 在骨髓和肺部作用于 MCp 以增强增殖能力。此外，肺中的 IL-9 刺激 CCR2+ mMC 从骨髓动员并募集到过敏性肺部。混合骨髓嵌合体表明，这些是 MCp 和 mMC 群体中的内在效应。在过敏性炎症的背景下，产生 IL-9 的 T 细胞既是增加肺部 MC 数量所必需的，也是充分的。重要的是，T 细胞 IL-9 介导的 MC 扩增是诱导抗原诱导和 MC 依赖性气道高反应性所必需的。综上所述，这些数据表明，T 细胞 IL-9 通过直接影响 MCp 的增殖和 mMC 的迁移来诱导肺部 MC 扩增和迁移，从而介导气道高反应性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6701/10482122/1430647b2a58/nihms-1925602-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6701/10482122/4934bc3fec04/nihms-1925602-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6701/10482122/d37898c62630/nihms-1925602-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6701/10482122/322f1fa4e5db/nihms-1925602-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6701/10482122/1d34bfedf167/nihms-1925602-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6701/10482122/7331ca62671f/nihms-1925602-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6701/10482122/1430647b2a58/nihms-1925602-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6701/10482122/4934bc3fec04/nihms-1925602-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6701/10482122/d37898c62630/nihms-1925602-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6701/10482122/322f1fa4e5db/nihms-1925602-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6701/10482122/1d34bfedf167/nihms-1925602-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6701/10482122/7331ca62671f/nihms-1925602-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6701/10482122/1430647b2a58/nihms-1925602-f0006.jpg

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