B-cell-derived IL-10 promotes allergic sensitization in asthma regulated by Bcl-3

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外文摘要：Aeroallergen sensitization,mainly mediated by lung epithelium and dendritic cells(DCs),is integral to allergic asthma pathogenesis and progression.IL-10 has a dual role in immune responses,as it inhibits myeloid cell activation but promotes B-cell responses and epithelial cell proliferation.Here,we report a proinflammatory function of B-cell-derived IL-10 modulated by Bcl-3 in allergic asthma.Specifically,Bcl-3-/-mice showed elevated IL-10 levels and were found to be highly vulnerable to allergic asthma induced by house dust mites(HDMs).IL-10 had a positive correlation with the levels of the DC chemoattractant CCL-20 in HDM-sensitized mice and in patients with asthma and induced a selective increase in CCL-20 production by mouse lung epithelial cells.Blockade of IL-10 or IL-10 receptors during sensitization dampened both HDM-induced sensitization and asthma development.IL-10 levels peaked 4 h post sensitization with HDM and IL-10 was primarily produced by B cells under Bcl-3-Blimp-1-Bcl-6 regulation.Mice lacking B-cell-derived IL-10 displayed decreased lung epithelial CCL-20 production and diminished DC recruitment to the lungs upon HDM sensitization,thereby demonstrating resistance to HDM-induced asthma.Moreover,responses to HDM stimulation in Bcl-3-/-mice lacking B-cell-derived IL-10 were comparable to those in Bcl-3+/+ mice.The results revealed an unexpected role of B-cell-derived IL-10 in promoting allergic sensitization and demonstrated that Bcl-3 prevents HDM-induced asthma by inhibiting B-cell-derived IL-10 production.Thus,targeting the Bcl-3/IL-10 axis to inhibit allergic sensitization is a promising approach for treating allergic asthma.

外文关键词：

Bcl-3Plasma cellIL-10Allergic sensitizationAirway inflammationAsthma

作者：

Guojun Qian、Wenxia Jiang、Donglin Sun、Zhun Sun、Anning Chen、Hongwei Fang、Jingyao Wang、Yongzhong Liu、Zhinan Yin、Haiming Wei、Hao Fang、Xiaoren Zhang

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作者单位：

Affiliated Cancer Hospital/Institute and GMU-GIBH Joint School of Life Sciences of Guangzhou Medical University,The Guangdong-Hong Kong-Macau Joint Laboratory for Cell Fate Regulation and Diseases,State Key Laboratory of Respiratory Disease,511436 Guangzhou,China

Key Laboratory of Anesthesiology(Shanghai Jiao Tong University),Ministry of Education,200001 Shanghai,China

Shanghai Institute of Nutrition and Health,Chinese Academy of Sciences,200031 Shanghai,China

Department of Anesthesiology,Zhongshan Hospital,Fudan University,200032 Shanghai,China

Shanghai Cancer Institute,Renji Hospital,Shanghai Jiao Tong University School of Medicine,200032 Shanghai,China

Zhuhai People's Hospital,Biomedical Translational Research Institute,Jinan University,510632 Guangzhou,China

Institute of Immunology,University of Science and Technology of China,230000 Hefei,China

Department of Anesthesiology,Minhang Hospital,Fudan University,201100 Shanghai,China

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基金：

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Program on Key ResearchDiscipline Construction Projects of Guangzhou Medical University

项目编号：

81901633919491022021YFA080470302-445-2301246XM

出版年：

2023

DOI：

10.1038/s41423-023-01079-w

中国免疫学杂志(英文版)

中国免疫学会

中国免疫学杂志(英文版)

CSTPCDCSCDSCI

影响因子：0.731

ISSN：1672-7681

年,卷(期)：2023.20(11)

参考文献量67