CIS controls the functional polarization of GM-CSF-derived macrophages
Journal Title
Cellular & Molecular Immunology
Publication Type
epub ahead of print
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.
Cis; Gm-csf; M1; M2; Macrophage
Research Division(s)
Immunology; Advanced Technology And Biology; Bioinformatics; Blood Cells And Blood Cancer; Cancer Biology And Stem Cells; Epigenetics And Development; Inflammation
PubMed ID
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Creation Date: 2022-12-13 03:13:15
Last Modified: 2022-12-14 01:18:04
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