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

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

作者地址："[Wang, Zhishuo; Du, Qizhen; Huang, Yuying; Li, Xuezhen; Cheng, Shipeng; Gu, Wangpeng; Zhu, Lin; Fan, Weiguo; Ma, Liyan; Ling, Zhiyang; Li, Dangsheng; Zhang, Yaguang; Sun, Bing] Univ Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci,State Key Lab Cell, 320 Yueyang Rd, Shanghai 200031, Peoples R China; [Yan, Chenghua] Jiangxi Univ Chinese Med, Coll Life Sci, Nanchang 330004, Peoples R China; [Zeng, Dan; Liu, Enmei] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ Key Lab Child Dev & Disorders, Chongqing Key Lab Pediat,Dept Resp Med,Childrens H, Chongqing, Peoples R China; [Zeng, Dan] Chongqing Gen Hosp, Dept Allergy, Chongqing, Peoples R China; [Mao, Ruizhi; Fang, Yiru] Shanghai Jiao Tong Univ, Clin Res Ctr, Shanghai Mental Hlth Ctr, Sch Med, Shanghai 200030, Peoples R China; [Mao, Ruizhi; Fang, Yiru] Shanghai Jiao Tong Univ, Shanghai Mental Hlth Ctr, Div Mood Disorders, Sch Med, Shanghai 200030, Peoples R China; [Gurram, Rama Krishna; Zhu, Jinfang] Natl Inst Allergy & Infect Dis, NIH, Lab Immune Syst Biol, Bethesda, MD 20892 USA; [Qiu, Ju] Univ Chinese Acad Sci, Shanghai Inst Nutr & Hlth, Chinese Acad Sci, CAS Key Lab Tissue Microenvironm & Tumor, Shanghai 200031, Peoples R China; [Fang, Yiru] CAS Ctr Excellence Brain Sci & Intelligence Techno, Shanghai 200031, Peoples R China; [Fang, Yiru] Shanghai Key Lab Psychot Disorders, Shanghai 201108, Peoples R China"

通信作者："Zhang, YG; Sun, B (通讯作者)，Univ Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci,State Key Lab Cell, 320 Yueyang Rd, Shanghai 200031, Peoples R China.; Yan, CH (通讯作者)，Jiangxi Univ Chinese Med, Coll Life Sci, Nanchang 330004, Peoples R China.; Liu, EM (通讯作者)，Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ Key Lab Child Dev & Disorders, Chongqing Key Lab Pediat,Dept Resp Med,Childrens H, Chongqing, Peoples R China.; Fang, YR (通讯作者)，Shanghai Jiao Tong Univ, Clin Res Ctr, Shanghai Mental Hlth Ctr, Sch Med, Shanghai 200030, Peoples R China.; Fang, YR (通讯作者)，Shanghai Jiao Tong Univ, Shanghai Mental Hlth Ctr, Div Mood Disorders, Sch Med, Shanghai 200030, Peoples R China.; Zhu, JF (通讯作者)，Natl Inst Allergy & Infect Dis, NIH, Lab Immune Syst Biol, Bethesda, MD 20892 USA.; Fang, YR (通讯作者)，CAS Ctr Excellence Brain Sci & Intelligence Techno, Shanghai 200031, Peoples R China.; Fang, YR (通讯作者)，Shanghai Key Lab Psychot Disorders, Shanghai 201108, Peoples R China."

来源：CELLULAR & MOLECULAR IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000937644200001

JCR分区：Q1

影响因子：24.1

年份：2023

卷号：20

期号：4

开始页：404

结束页：418

文献类型：Article

关键词：Serotonin (5-HT); HTR2A; DOI; Group 2 innate lymphoid cell; Type 2 lung inflammation

摘要："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/+)center dot 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."

基金机构："Ministry of Science and Technology of China [2018YFA0507402]; National Natural Science Foundation of China [81771465, 81930033]; Shanghai Science and Technology Innovation Action [21ZR1470600]; Youth Innovation Promotion Association of the Chinese Academy of Sciences [2022264]; Science and Technology Project of the Department of Education of Jiangxi Province [GJJ211248]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health [1ZIA-AI-001169]; US?China Biomedical Collaborative Research Program [AI-129775]; Center for Excellence in Molecular Cell Science, CAS"

基金资助正文："This work was supported by the Ministry of Science and Technology of China (2018YFA0507402), the National Natural Science Foundation of China (32000667), the Shanghai Science and Technology Innovation Action (21ZR1470600), and the Youth Innovation Promotion Association of the Chinese Academy of Sciences (2022264). This work was also supported by the National Natural Science Foundation of China (81771465 and 81930033) and the Science and Technology Project of the Department of Education of Jiangxi Province (GJJ211248). RKG and JZ are supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health (grant 1ZIA-AI-001169) and the US?China Biomedical Collaborative Research Program (grant AI-129775). We are grateful to Guomei Lin for breeding the animals and for animal management. We also acknowledge the individuals involved in technical support at the Center for Excellence in Molecular Cell Science, CAS, including the Core Facility for Cell Biology, the Animal Core Facility, the Core Facility of Molecular Biology and the Chemical Biology Core Facility."