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OPINION

Promises and limitations of immune cell-based therapies in neurological disorders

Nature Reviews Neurology volume 14, pages 559–568 (2018)Cite this article

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Abstract

The healthy immune system has natural checkpoints that temper pernicious inflammation. Cells mediating these checkpoints include regulatory T cells, regulatory B cells, regulatory dendritic cells, microglia, macrophages and monocytes. Here, we highlight discoveries on the beneficial functions of regulatory immune cells and their mechanisms of action and evaluate their potential use as novel cell-based therapies for brain disorders. Regulatory immune cell therapies have the potential not only to mitigate the exacerbation of brain injury by inflammation but also to promote an active post-injury brain repair programme. By harnessing the reparative properties of these cells, we can reduce over-reliance on medications that mask clinical symptoms but fail to impede or reverse the progression of brain disorders. Although these discoveries encourage further testing and genetic engineering of regulatory immune cells for the clinical management of neurological disorders, a number of challenges must be surmounted to improve their safety and efficacy in humans.

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Fig. 1: Mechanisms underlying regulatory T cell-mediated neuroprotection or regeneration.
Fig. 2: Timeline of some seminal findings in adoptive cell therapies.

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Acknowledgements

X.H. is supported by grants from the US National Institutes of Health (NIH) (NS094573 and NS092618). R.K.L. is supported by the NIH (1R15NS093539). A.W.T. is supported by the NIH (1R01AI118777 and U19AI131453). J.C. is supported by grants from the NIH (NS105430, NS095671, NS095029 and NS089534), the US Veterans Affairs (VA) Merit Review awards (I01BX003377 and I01BX002495) and the VA Senior Research Career Scientist Award.

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Authors and Affiliations

  1. Pittsburgh Institute of Brain Disorders and Recovery and Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Xiaoming Hu, Fang Yu, Yuguo Xia, Lawrence R. Wechsler & Jun Chen

  2. Division of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA, USA

    Rehana K. Leak

  3. Starzl Transplantation Institute, Department of Surgery and Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Angus W. Thomson

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  1. Xiaoming Hu
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All authors contributed to the review and editing of the manuscript before submission. X.H., R.K.L., A.W.T., F.Y., Y.X. and J.C. researched and wrote the article. X.H., R.K.L., A.W.T. and J.C. contributed substantially to the discussion of content.

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Correspondence to Jun Chen.

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Hu, X., Leak, R.K., Thomson, A.W. et al. Promises and limitations of immune cell-based therapies in neurological disorders. Nat Rev Neurol 14, 559–568 (2018). https://doi.org/10.1038/s41582-018-0028-5

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