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Macrophages: Biology and Role in the Pathology of Diseases pp 497–508Cite as

Regulation of Macrophage Polarization by the STAT–SOCS Signaling Axis

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Abstract

Macrophage polarization has many consequences for normal immune function, with M1-like macrophages required for host defense in response to viral and bacterial pathogens, and M2-like macrophages involved in the response to helminth infection and repair of tissue damage. Dysregulation of macrophage function also has important implications for excessive or inappropriate immune responses such as those observed in sepsis, autoimmunity and allergy and asthma, in addition to anti-tumor immunity. Macrophage polarization is regulated both intrinsically by changes in the epigenetic landscape and extrinsically, in response to pathogenic stimuli. An important component of the latter are the cytokines, in particular interferon (IFN)γ and interleukins (IL)-4 and 13, which classically drive cellular responses through activation of the JAK/STAT pathway. The Suppressors Of Cytokine Signaling (SOCS) proteins have emerged as important negative regulators of JAK/STAT signaling, functioning largely as part of a negative feedback loop. Here we review those studies that have attempted to address the role of SOCS proteins in macrophage polarization and highlight areas for further investigation.

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Acknowledgments

We thank Peter Maltezos for the figure production. Sandra E. Nicholson is supported by an Australian National Health and Medical Research Council (NHMRC) Fellowship, as well as an NHMRC IRIISS grant 361646 and a Victorian State Government Operational Infrastructure Scheme grant. Peter J. Murray is supported by grants from the Hartwell Foundation, the National Institutes of Health Cancer Center Core grant, AI062921, and the American Lebanese Syrian Associated Charities.

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Authors and Affiliations

  1. Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia

    Sandra E. Nicholson

  2. Department of Medical Biology, the University of Melbourne, Parkville, VIC, Australia

    Sandra E. Nicholson

  3. Departments of Infectious Diseases & Immunology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Peter J. Murray

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  1. Sandra E. Nicholson
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  2. Peter J. Murray
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Editors and Affiliations

  1. Singapore Immunology Network (SIgN) Biomedical Sciences Institutes, A*STAR, Singapore, Singapore

    Subhra K. Biswas

  2. IRCCS Humanitas Clinical and Research Institute, Humanitas University, Rozzano, Italy

    Alberto Mantovani

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Nicholson, S.E., Murray, P.J. (2014). Regulation of Macrophage Polarization by the STAT–SOCS Signaling Axis. In: Biswas, S., Mantovani, A. (eds) Macrophages: Biology and Role in the Pathology of Diseases. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1311-4_24

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