Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/137317
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Type: Journal article
Title: CIS controls the functional polarization of GM-CSF-derived macrophages
Author: Zhang, S.
Rautela, J.
Bediaga, N.G.
Kolesnik, T.B.
You, Y.
Nie, J.
Dagley, L.F.
Bedo, J.
Wang, H.
Sun, L.
Sutherland, R.
Surgenor, E.
Iannarella, N.
Allan, R.
Souza-Fonseca-Guimaraes, F.
Xie, Y.
Wang, Q.
Zhang, Y.
Xu, Y.
Nutt, S.L.
et al.
Citation: Cellular and Molecular Immunology, 2022; 20(1):65-79
Publisher: Springer Nature
Issue Date: 2022
ISSN: 1672-7681
2042-0226
Statement of
Responsibility: 
Shengbo Zhang ... Naiara G. Bediaga ... et al.
Abstract: 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.
Keywords: Monocytes
Macrophages
Granulocyte-Macrophage Colony-Stimulating Factor
Cytokines
Cell Differentiation
Interferon Regulatory Factors
Rights: © 2022, The Author(s), under exclusive licence to CSI and USTC
DOI: 10.1038/s41423-022-00957-z
Grant ID: http://purl.org/au-research/grants/nhmrc/1037321
http://purl.org/au-research/grants/nhmrc/1105209
http://purl.org/au-research/grants/nhmrc/1143976
http://purl.org/au-research/grants/nhmrc/1150425
http://purl.org/au-research/grants/nhmrc/1080321
http://purl.org/au-research/grants/nhmrc/1196335
http://purl.org/au-research/grants/nhmrc/5575500
http://purl.org/au-research/grants/nhmrc/1054925
http://purl.org/au-research/grants/nhmrc/1048278
http://purl.org/au-research/grants/nhmrc/361646
Appears in Collections:Medicine publications

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