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Brain regulatory T cells

Nature Reviews Immunology volume 24, pages 326–337 (2024)Cite this article

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Abstract

The brain, long thought to be isolated from the peripheral immune system, is increasingly recognized to be integrated into a systemic immunological network. These conduits of immune–brain interaction and immunosurveillance processes necessitate the presence of complementary immunoregulatory mechanisms, of which brain regulatory T cells (Treg cells) are likely a key facet. Treg cells represent a dynamic population in the brain, with continual influx, specialization to a brain-residency phenotype and relatively rapid displacement by newly incoming cells. In addition to their functions in suppressing adaptive immunity, an emerging view is that Treg cells in the brain dampen down glial reactivity in response to a range of neurological insults, and directly assist in multiple regenerative and reparative processes during tissue pathology. The utility and malleability of the brain Treg cell population make it an attractive therapeutic target across the full spectrum of neurological conditions, ranging from neuroinflammatory to neurodegenerative and even psychiatric diseases. Therapeutic modalities currently under intense development include Treg cell therapy, IL-2 therapy to boost Treg cell numbers and multiple innovative approaches to couple these therapeutics to brain delivery mechanisms for enhanced potency. Here we review the state of the art of brain Treg cell knowledge together with the potential avenues for future integration into medical practice.

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Fig. 1: Key features of brain regulatory T cells.
Fig. 2: Potential migration routes for brain regulatory T cells.
Fig. 3: Harnessing brain regulatory T cells to treat neuroinflammation.

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Authors and Affiliations

  1. Department of Pathology, University of Cambridge, Cambridge, UK

    Adrian Liston

  2. Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium

    Emanuela Pasciuto

  3. Center for Molecular Neurology, VIB, Antwerp, Belgium

    Emanuela Pasciuto

  4. School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, UK

    Denise C. Fitzgerald

  5. Department of Neurosciences, KU Leuven, Leuven, Belgium

    Lidia Yshii

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The authors contributed equally to all aspects of the article.

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Correspondence to Adrian Liston, Emanuela Pasciuto, Denise C. Fitzgerald or Lidia Yshii.

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The VIB and Babraham Institute are owners of patent applications PCT/GB2020/052148 and GB2118073.2, commented on in this work, with A.L., E.P. and L.Y. potential financial beneficiaries of commercialization. D.C.F. declares no competing interests.

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Liston, A., Pasciuto, E., Fitzgerald, D.C. et al. Brain regulatory T cells. Nat Rev Immunol 24, 326–337 (2024). https://doi.org/10.1038/s41577-023-00960-z

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