Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/137317
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
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 |
Published version: | http://dx.doi.org/10.1038/s41423-022-00957-z |
Appears in Collections: | Medicine publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.