Salt-inducible kinase 1 is a key gene in suppressing EVD68-induced asthma by modulating antiviral immunityOA
Asthma is a complex inflammatory disease of the airways,affecting over 300 million individuals globally,Infection with enterovirus D68(EV-D68)has been identified as a risk factor for asthma,However,the biological mechanisms of EV-D68-related asthma remain unclear,In this study,using machine learning techniques,we identified salt-inducible kinase 1(SIK1),which plays a crucial role in associating with the asthma phenotype and EV-D68 infection,Concretely,a negative correlation between SIK1 expression and asthma risk has been revealed through Mendelian randomization,Immune infiltration analyses showed that SIK1 was negatively correlated with mast cell activity and positively correlated with T cell responses,Using weighted gene co-expression network analysis,we demonstrated SIK1''s role in antiviral immune responses in asthma,Further in vitro and in vivo experiments confirmed that SIK1 was up-regulated in virus infection,and it exerted antiviral effects in various viral infections,Finally,in the asthma exacerbation model of HDM combined with EV-D68 infection,SIK1 activation effectively mitigated EV-D68-induced asthma exacerbation in mice,Taken together,our findings suggest that SIK1 serves as a protective factor in EV-D68-induced asthma by modulating antiviral immune responses,which provide new insights into potential treatments for EV-D68-induced asthma attacks.
Juntong Liu;Yue Wang;Lingyun Zou;Xinyue Han;Mingqi Lv;Xichuan Deng;Jingjing Liao;Guangchao Zang;Lei Xu;Tianle Gu;Nan Lu;Guangyuan Zhang
Pathogen Biology and Immunology Laboratory,Lab Teaching & Management Center,School of Basic Medical Sciences,Chongqing Medical University,Chongqing 400016,ChinaPathogen Biology and Immunology Laboratory,Lab Teaching & Management Center,School of Basic Medical Sciences,Chongqing Medical University,Chongqing 400016,ChinaDepartment of Clinical Data Research,Chongqing Emergency Medical Center,Chongqing University Central Hospital,Chongqing University,Chongqing 400014,ChinaPathogen Biology and Immunology Laboratory,Lab Teaching & Management Center,School of Basic Medical Sciences,Chongqing Medical University,Chongqing 400016,ChinaPathogen Biology and Immunology Laboratory,Lab Teaching & Management Center,School of Basic Medical Sciences,Chongqing Medical University,Chongqing 400016,ChinaPathogen Biology and Immunology Laboratory,Lab Teaching & Management Center,School of Basic Medical Sciences,Chongqing Medical University,Chongqing 400016,ChinaPathogen Biology and Immunology Laboratory,Lab Teaching & Management Center,School of Basic Medical Sciences,Chongqing Medical University,Chongqing 400016,ChinaPathogen Biology and Immunology Laboratory,Lab Teaching & Management Center,School of Basic Medical Sciences,Chongqing Medical University,Chongqing 400016,ChinaPathogen Biology and Immunology Laboratory,Lab Teaching & Management Center,School of Basic Medical Sciences,Chongqing Medical University,Chongqing 400016,ChinaPathogen Biology and Immunology Laboratory,Lab Teaching & Management Center,School of Basic Medical Sciences,Chongqing Medical University,Chongqing 400016,ChinaPathogen Biology and Immunology Laboratory,Lab Teaching & Management Center,School of Basic Medical Sciences,Chongqing Medical University,Chongqing 400016,ChinaPathogen Biology and Immunology Laboratory,Lab Teaching & Management Center,School of Basic Medical Sciences,Chongqing Medical University,Chongqing 400016,China
医药卫生
Antiviral immunityAsthmaEV-D68SIK1Virus
《Genes & Diseases》 2026 (3)
P.456-470,15
supported by grants from the National Natural Science Foundation of China(No.31600139)the Chongqing Municipal Education Commission of China(No.CSTB2024NSCQ-KJFZMSX0067)the Project of Undergraduates Innovating Experiment and the Project of Tutorial System of Excellent Medical Undergraduate in Lab Teaching and Management Center of Chongqing Medical University(China)(No.202211,S202410631068,202510631005,LTMCMTS202310,LTMCMTS202311,LTMCMTS202312,LTMCMTS202458,LTMCMTS202459,LTMCMTS202460,LTMCMTS202461)the Program for Youth Innovation in Future Medicine,Chongqing Medical University(China)(No.W0160)the Chongqing Medical Scientific Research Project(Joint Project of Chongqing Health Commission and Science and Technology Bureau(No.2024zDxM011)the Natural Science Foundation of Chongqing,China(No.CSTB2023NSCQ-MSX0237).
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