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

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dc.contributor.authorZhang, S.
dc.contributor.authorRautela, J.
dc.contributor.authorBediaga, N.G.
dc.contributor.authorKolesnik, T.B.
dc.contributor.authorYou, Y.
dc.contributor.authorNie, J.
dc.contributor.authorDagley, L.F.
dc.contributor.authorBedo, J.
dc.contributor.authorWang, H.
dc.contributor.authorSun, L.
dc.contributor.authorSutherland, R.
dc.contributor.authorSurgenor, E.
dc.contributor.authorIannarella, N.
dc.contributor.authorAllan, R.
dc.contributor.authorSouza-Fonseca-Guimaraes, F.
dc.contributor.authorXie, Y.
dc.contributor.authorWang, Q.
dc.contributor.authorZhang, Y.
dc.contributor.authorXu, Y.
dc.contributor.authorNutt, S.L.
dc.contributor.authoret al.
dc.date.issued2022
dc.description.abstractThe 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.
dc.description.statementofresponsibilityShengbo Zhang ... Naiara G. Bediaga ... et al.
dc.identifier.citationCellular and Molecular Immunology, 2022; 20(1):65-79
dc.identifier.doi10.1038/s41423-022-00957-z
dc.identifier.issn1672-7681
dc.identifier.issn2042-0226
dc.identifier.urihttps://hdl.handle.net/2440/137317
dc.language.isoen
dc.publisherSpringer Nature
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1037321
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1105209
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1143976
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1150425
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1080321
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1196335
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/5575500
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1054925
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1048278
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/361646
dc.rights© 2022, The Author(s), under exclusive licence to CSI and USTC
dc.source.urihttps://doi.org/10.1038/s41423-022-00957-z
dc.subjectMonocytes
dc.subjectMacrophages
dc.subjectGranulocyte-Macrophage Colony-Stimulating Factor
dc.subjectCytokines
dc.subjectCell Differentiation
dc.subjectInterferon Regulatory Factors
dc.subject.meshMonocytes
dc.subject.meshMacrophages
dc.subject.meshGranulocyte-Macrophage Colony-Stimulating Factor
dc.subject.meshCytokines
dc.subject.meshCell Differentiation
dc.subject.meshInterferon Regulatory Factors
dc.titleCIS controls the functional polarization of GM-CSF-derived macrophages
dc.typeJournal article
pubs.publication-statusPublished

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