首页|HTR2A agonists play a therapeutic role by restricting ILC2 activation in papain-induced lung inflammation

HTR2A agonists play a therapeutic role by restricting ILC2 activation in papain-induced lung inflammation

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Group 2 innate lymphoid cells(ILC2s)are a category of heterogeneous cells that produce the cytokines IL-5 and IL-13,which mediate the type 2 immune response.However,specific drug targets on lung ILC2s have rarely been reported.Previous studies have shown that type 2 cytokines,such as IL-5 and IL-13,are related to depression.Here,we demonstrated the negative correlation between the depression-associated monoamine neurotransmitter serotonin and secretion of the cytokines IL-5 and IL-13 by ILC2s in individuals with depression.Interestingly,serotonin ameliorates papain-induced lung inflammation by suppressing ILC2 activation.Our data showed that the serotonin receptor HTR2A was highly expressed on ILC2s from mouse lungs and human PBMCs.Furthermore,an HTR2A selective agonist(DOI)impaired ILC2 activation and alleviated the type 2 immune response in vivo and in vitro.Mice with ILC2-specific depletion of HTR2A(Il5～(cre/+)·Htr2a～(flox/flox) mice)abolished the DOI-mediated inhibition of ILC2s in a papain-induced mouse model of inflammation.In conclusion,serotonin and DOI could restrict the type 2 lung immune response,indicating a potential treatment strategy for type 2 lung inflammation by targeting HTR2A on ST2+ILC2s.

Serotonin(5-HT)HTR2ADOIGroup 2 innate lymphoid cellType 2 lung inflammation

Zhishuo Wang、Chenghua Yan、Qizhen Du、Yuying Huang、Xuezhen Li、Dan Zeng、Ruizhi Mao、Rama Krishna Gurram、Shipeng Cheng、Wangpeng Gu、Lin Zhu、Weiguo Fan、Liyan Ma、Zhiyang Ling、Ju Qiu、Dangsheng Li、Enmei Liu、Yaguang Zhang、Yiru Fang、Jinfang Zhu、Bing Sun

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State Key Laboratory of Cell Biology,CAS Center for Excellence in Molecular Cell Science,Shanghai Institute of Biochemistry and Cell Biology,Chinese Academy of Sciences,University of Chinese Academy of Sciences,320 Yueyang Road,Shanghai 200031,China

College of Life Sciences,Jiangxi University of Chinese Medicine,Nanchang 330004,China

Department of Respiratory Medicine Children's Hospital of Chongqing Medical University,National Clinical Research Center for Child Health and Disorders,Ministry of Education Key Laboratory of Child Development and Disorders,Chongqing Key Laboratory of Pediatrics,Chongqing,China

Department of Allergy,Chongqing General Hospital,Chongqing,China

Clinical Research Center and Division of Mood Disorders,Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine,Shanghai 200030,China

Laboratory of Immune System Biology,National Institute of Allergy and Infectious Diseases,National Institutes of Health,Bethesda,MD 20892,USA

CAS Key Laboratory of Tissue Microenvironment and Tumor,Shanghai Institute of Nutrition and Health,University of Chinese Academy of Sciences,Chinese Academy of Sciences,Shanghai 200031,China

CAS Center for Excellence in Brain Science and Intelligence Technology,Shanghai 200031,China

Shanghai Key Laboratory of Psychotic Disorders,Shanghai 201108,China

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Ministry of Science and Technology of ChinaNational Natural Science Foundation of ChinaShanghai Science and Technology Innovation ActionYouth Innovation Promotion Association of the Chinese Academy of SciencesNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaScience and Technology Project of the Department of Education of Jiangxi ProvinceDivision of Intramural Research,National Institute of Allergy and Infectious Diseases,National Institutes of HealthUS-China Biomedical Collaborative Research Program

2018YFA05074023200066721ZR147060020222648177146581930033GJJ2112481ZIA-AI-001169AI-129775

2023

10.1038/s41423-023-00982-6

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(4)
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