首页|CIS controls the functional polarization of GM-CSF-derived macrophages

CIS controls the functional polarization of GM-CSF-derived macrophages

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The cytokine granulocyte-macrophage-colony stimulating factor(GM-CSF)possesses the capacity to differentiate monocytes into macrophages(MØs)with opposing functions,namely,proinflammatory M1-like MØs and immunosuppressive M2-like MØs.Despite the importance of these opposing biological outcomes,the intrinsic mechanism that regulates the functional polarization of MØs under GM-CSF signaling remains elusive.Here,we showed that GM-CSF-induced MØ polarization resulted in the expression of cytokine-inducible SH2-containing protein(CIS)and that CIS deficiency skewed the differentiation of monocytes toward immunosuppressive M2-like MØs.CIS deficiency resulted in hyperactivation of the JAK-STAT5 signaling pathway,consequently promoting downregulation of the transcription factor Interferon Regulatory Factor 8(IRF8).Loss-and gain-of-function approaches highlighted IRF8 as a critical regulator of the M1-like polarization program.In vivo,CIS deficiency induced the differentiation of M2-like macrophages,which promoted strong Th2 immune responses characterized by the development of severe experimental asthma.Collectively,our results reveal a CIS-modulated mechanism that clarifies the opposing actions of GM-CSF in MØ differentiation and uncovers the role of GM-CSF in controlling allergic inflammation.

CISGM-CSFMacrophageM2M1

Shengbo Zhang、Jai Rautela、Naiara G.Bediaga、Tatiana B.Kolesnik、Yue You、Junli Nie、Laura F.Dagley、Justin Bedo、Hanqing Wang、Li Sun、Robyn Sutherland、Elliot Surgenor、Nadia Iannarella、Rhys Allan、Fernando Souza-Fonseca-Guimaraes、Yi Xie、Qike Wang、Yuxia Zhang、Yuekang Xu、Stephen L.Nutt、Andrew M.Lew、Nicholas D.Huntington、Sandra E.Nicholson、Micha?l Chopin、Yifan Zhan

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Walter and Eliza Hall Institute of Medical Research,Parkville,VIC,Australia

Department of Medical Biology,University of Melbourne,Parkville,VIC,Australia

Department of Biochemistry and Molecular Biology,Biomedicine Discovery Institute,Monash University,Clayton,VIC,Australia

oNKo-Innate Pty Ltd,Moonee Ponds,VIC,Australia

Department of Computing and Information Systems,University of Melbourne,Parkville,VIC,Australia

Department of Respiratory Medicine,Guangzhou Institute of Pediatrics,Guangzhou Women and Children's Medical Centre,State Key Laboratory of Respiratory Diseases,Guangzhou Medical University,Guangzhou,Guangdong,China

College of Biological Science,Anhui Normal University,Hefei,China

University of Queensland Diamantina Institute,University of Queensland,Translational Research Institute,Brisbane,QLD,Australia

Program in Cardiovascular and Metabolic Disorders,Duke-NUS Medical School,Duke,Singapore

Drug Discovery,Shanghai Huaota Biopharm,Shanghai,China

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National Health and Medical Research Council of Australia(NHMRC)grantsNational Health and Medical Research Council of Australia(NHMRC)grantsNational Health and Medical Research Council of Australia(NHMRC)grantsNational Health and Medical Research Council of Australia(NHMRC)grantsNational Health and Medical Research Council of Australia(NHMRC)grantsNational Health and Medical Research Council of Australia(NHMRC)grantsNational Health and Medical Research Council of Australia(NHMRC)grantsNational Health and Medical Research Council of Australia(NHMRC)grantsNational Health and Medical Research Council of Australia(NHMRC)grantsan NHMRC Independent Research Institutes Infrastructure Support Scheme granta Victorian State Government Operational Infrastructure Support grantStafford Fox Medical Research Foundation

103732111052091143976115042510803211196335557550010549251048278361646

2023

10.1038/s41423-022-00957-z

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(1)
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