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Regulatory T lymphocytes as a therapy for ischemic stroke

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Abstract

Unrestrained excessive inflammatory responses exacerbate ischemic brain injury and impede post-stroke brain recovery. CD4+CD25+Foxp3+ regulatory T (Treg) cells play important immunosuppressive roles to curtail inflammatory responses and regain immune homeostasis after stroke. Accumulating evidence confirms that Treg cells are neuroprotective at the acute stage after stroke and promote brain repair at the chronic phases. The beneficial effects of Treg cells are mediated by diverse mechanisms involving cell–cell interactions and soluble factor release. Multiple types of cells, including both immune cells and non-immune CNS cells, have been identified to be cellular targets of Treg cells. In this review, we summarize recent findings regarding the function of Treg cells in ischemic stroke and the underlying cellular and molecular mechanisms. The protective and reparative properties of Treg cells endorse them as good candidates for immune therapy. Strategies that boost the numbers and functions of Treg cells have been actively develo** in the fields of transplantation and autoimmune diseases. We discuss the approaches for Treg cell expansion that have been tested in stroke models. The application of these approaches to stroke patients may bring new hope for stroke treatments.

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Funding

**aoming Hu is supported by a VA grant (I01 BX003651) and a NIH grant (R01NS094573). AWT is supported by NIH grants AI R01 118777, U01 AI136779, and U19 AI 131453. Rimi Hazra is supported by the pilot grants from the Vascular Medicine Institute, the Hemophilia Center of Western Pennsylvania, Vitalant and Winters Foundation of Pittsburgh.

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Authors and Affiliations

  1. Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA, 15261, USA

    Miao Wang & **aoming Hu

  2. Pittsburgh Institute of Brain Disorders and Recovery and Department of Neurology, School of Medicine, University of Pittsburgh, 200 Lothrop Street, SBST, Pittsburgh, PA, 15213, USA

    Miao Wang, Fang Yu, Aditi Junagade & **aoming Hu

  3. Department of Surgery and Department of Immunology, Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA

    Angus W. Thomson

  4. Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA

    Rimi Hazra

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Wang, M., Thomson, A.W., Yu, F. et al. Regulatory T lymphocytes as a therapy for ischemic stroke. Semin Immunopathol 45, 329–346 (2023). https://doi.org/10.1007/s00281-022-00975-z

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