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

Date

2022

Authors

Zhang, S.
Rautela, J.
Bediaga, N.G.
Kolesnik, T.B.
You, Y.
Nie, J.
Dagley, L.F.
Bedo, J.
Wang, H.
Sun, L.

Editors

Advisors

Journal Title

Journal ISSN

Volume Title

Type:

Journal article

Citation

Cellular and Molecular Immunology, 2022; 20(1):65-79

Statement of Responsibility

Shengbo Zhang ... Naiara G. Bediaga ... et al.

Conference Name

DOI

10.1038/s41423-022-00957-z

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.

School/Discipline

Dissertation Note

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Rights

© 2022, The Author(s), under exclusive licence to CSI and USTC

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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

Published Version

https://doi.org/10.1038/s41423-022-00957-z

Call number

Persistent link to this record

https://hdl.handle.net/2440/137317