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  • Review Article
  • Published:

Myeloid cells — targets of medication in multiple sclerosis

Nature Reviews Neurology volume 12, pages 539–551 (2016)Cite this article

Subjects

Key Points

  • The roles of lymphocytes in multiple sclerosis (MS) pathophysiology are well known, but myeloid cells, including monocytes, macrophages, microglia and dendritic cells, are also important

  • Interactions between lymphocytes and myeloid cells exacerbate injurious processes

  • Myeloid cells are not the main targets of immunomodulators that are used to treat MS, but are still affected by them in disease-relevant ways

  • The actions of MS immunomodulators on myeloid cells contribute to the clinical efficacy of these therapeutic approaches

Abstract

Discussions of multiple sclerosis (MS) pathophysiology tend to focus on T cells and B cells of the adaptive immune response. The innate immune system is less commonly considered in this context, although dendritic cells, monocytes, macrophages and microglia — collectively referred to as myeloid cells — have prominent roles in MS pathogenesis. These populations of myeloid cells function as antigen-presenting cells and effector cells in neuroinflammation. Furthermore, a vicious cycle of interactions between T cells and myeloid cells exacerbates pathology. Several disease-modifying therapies are now available to treat MS, and insights into their mechanisms of action have largely focused on the adaptive immune system, but these therapies also have important effects on myeloid cells. In this Review, we discuss the evidence for the roles of myeloid cells in MS and the experimental autoimmune encephalomyelitis model of MS, and consider how interactions between myeloid cells and T cells and/or B cells promote MS pathology. Finally, we discuss the direct and indirect effects of existing MS medications on myeloid cells.

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Figure 1: Development of myeloid cells.
Figure 2: Characteristics of macrophage subsets.
Figure 3: Postulated immune cascades in multiple sclerosis.
Figure 4: Proposed actions of disease-modifying multiple sclerosis therapies on myeloid cells.

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Acknowledgements

The authors' research is supported by grants from the Canadian Institutes of Health Research, the Alberta Innovates–Health Solutions CRIO Team programme, and the Multiple Sclerosis Society of Canada.

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  1. Hotchkiss Brain Institute and the Department of Clinical Neurosciences, University of Calgary, 3330 Hospital Drive, Calgary, T2N 4N1, Alberta, Canada

    Manoj K. Mishra & V. Wee Yong

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Both authors contributed equally to all aspects of the manuscript.

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Correspondence to V. Wee Yong.

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Competing interests

V.W.Y. acknowledges previous unrestricted operating grant funding from EMD-Serono, Novartis and Teva Pharmaceuticals, and previous and current unrestricted educational grants from Biogen-Idec, EMD-Serono, Genyzme, Novartis, Roche and Teva Neuroscience. V.W.Y. has received honoraria for seminar presentations from Biogen-Idec, Genzyme, Novartis and Teva Neuroscience. M.K.M. declares no competing interests.

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Mishra, M., Yong, V. Myeloid cells — targets of medication in multiple sclerosis. Nat Rev Neurol 12, 539–551 (2016). https://doi.org/10.1038/nrneurol.2016.110

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