DuPage, M. & Bluestone, J. A. Harnessing the plasticity of CD4+ T cells to treat immune-mediated disease. Nat. Rev. Immunol. 16, 149–163 (2016).
Article CAS PubMed Google Scholar
Machhi, J. et al. Harnessing regulatory T cell neuroprotective activities for treatment of neurodegenerative disorders. Mol. Neurodegener. 15, 32 (2020).
Article PubMed PubMed Central Google Scholar
Panduro, M., Benoist, C. & Mathis, D. Tissue Tregs. Annu. Rev. Immunol. 34, 609–633 (2016).
Article CAS PubMed PubMed Central Google Scholar
Feuerer, M. et al. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat. Med. 15, 930–939 (2009).
Article CAS PubMed PubMed Central Google Scholar
Burzyn, D. et al. A special population of regulatory T cells potentiates muscle repair. Cell 155, 1282–1295 (2013).
Article CAS PubMed PubMed Central Google Scholar
Arpaia, N. et al. A distinct function of regulatory T cells in tissue protection. Cell 162, 1078–1089 (2015).
Article CAS PubMed PubMed Central Google Scholar
Schiering, C. et al. The alarmin IL-33 promotes regulatory T-cell function in the intestine. Nature 513, 564–568 (2014).
Article CAS PubMed PubMed Central Google Scholar
Rosenblum, M. D. et al. Response to self antigen imprints regulatory memory in tissues. Nature 480, 538–542 (2011).
Article CAS PubMed PubMed Central Google Scholar
Delacher, M. et al. Genome-wide DNA-methylation landscape defines specialization of regulatory T cells in tissues. Nat. Immunol. 18, 1160–1172 (2017).
Article CAS PubMed PubMed Central Google Scholar
Burton, O. et al. The tissue-resident regulatory T cell pool is shaped by transient multi-tissue migration and a conserved residency program. Preprint at bioRxiv https://doi.org/10.1101/2023.08.14.553196 (2023).
Pasciuto, E. et al. Microglia require CD4 T cells to complete the fetal-to-adult transition. Cell 182, 625–640.e24 (2020). This study is the first to analyse the phenotype, kinetics and function of brain-resident Tregcells in the homeostatic state in mice and humans.
Article CAS PubMed PubMed Central Google Scholar
Ito, M. et al. Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery. Nature 565, 246–250 (2019). This study unveils innovative mechanisms through which Tregcells actively participate in the process of tissue repair following brain injury.
Article CAS PubMed Google Scholar
Garg, G. et al. Blimp1 prevents methylation of Foxp3 and loss of regulatory T cell identity at sites of inflammation. Cell Rep. 26, 1854–1868.e5 (2019).
Article CAS PubMed PubMed Central Google Scholar
O’Connor, R. A., Malpass, K. H. & Anderton, S. M. The inflamed central nervous system drives the activation and rapid proliferation of Foxp3+ regulatory T cells. J. Immunol. 179, 958–966 (2007).
Korn, T. et al. Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation. Nat. Med. 13, 423–431 (2007).
Article CAS PubMed PubMed Central Google Scholar
Yang, S., Fujikado, N., Kolodin, D., Benoist, C. & Mathis, D. Immune tolerance. Regulatory T cells generated early in life play a distinct role in maintaining self-tolerance. Science 348, 589–594 (2015).
Article CAS PubMed PubMed Central Google Scholar
Schlager, C. et al. Effector T-cell trafficking between the leptomeninges and the cerebrospinal fluid. Nature 530, 349–353 (2016).
Medawar, P. B. Immunity to homologous grafted skin; the fate of skin homografts transplanted to the brain, to subcutaneous tissue, and to the anterior chamber of the eye. Br. J. Exp. Pathol. 29, 58–69 (1948).
CAS PubMed PubMed Central Google Scholar
Proulx, S. T. & Engelhardt, B. Central nervous system zoning: how brain barriers establish subdivisions for CNS immune privilege and immune surveillance. J. Intern. Med. 292, 47–67 (2022).
Article PubMed PubMed Central Google Scholar
Nishihara, H. et al. Human CD4+ T cell subsets differ in their abilities to cross endothelial and epithelial brain barriers in vitro. Fluids Barriers CNS 17, 3 (2020).
Article CAS PubMed PubMed Central Google Scholar
Li, P. et al. C–C chemokine receptor type 5 (CCR5)-mediated docking of transferred Tregs protects against early blood–brain barrier disruption after stroke. J. Am. Heart Assoc. 6, e006387 (2017).
Article PubMed PubMed Central Google Scholar
Da Mesquita, S. et al. Aging-associated deficit in CCR7 is linked to worsened glymphatic function, cognition, neuroinflammation, and β-amyloid pathology. Sci. Adv. 7, eabe4601 (2021).
Article PubMed PubMed Central Google Scholar
Ben-Yehuda, H. et al. Key role of the CCR2–CCL2 axis in disease modification in a mouse model of tauopathy. Mol. Neurodegener. 16, 39 (2021).
Article CAS PubMed PubMed Central Google Scholar
Lucaciu, A. et al. A sphingosine 1-phosphate gradient is linked to the cerebral recruitment of T helper and regulatory T helper cells during acute ischemic stroke. Int. J. Mol. Sci. 21, 6242 (2020).
Article CAS PubMed PubMed Central Google Scholar
Lee, H. T. et al. A crucial role of CXCL14 for promoting regulatory T cells activation in stroke. Theranostics 7, 855–875 (2017).
Article CAS PubMed PubMed Central Google Scholar
Hrastelj, J. et al. CSF-resident CD4+ T-cells display a distinct gene expression profile with relevance to immune surveillance and multiple sclerosis. Brain Commun. 3, fcab155 (2021).
Article PubMed PubMed Central Google Scholar
Kivisakk, P. et al. Human cerebrospinal fluid central memory CD4+ T cells: evidence for trafficking through choroid plexus and meninges via P-selectin. Proc. Natl Acad. Sci. USA 100, 8389–8394 (2003).
Article PubMed PubMed Central Google Scholar
Llovera, G. et al. The choroid plexus is a key cerebral invasion route for T cells after stroke. Acta Neuropathol. 134, 851–868 (2017).
Article CAS PubMed Google Scholar
Wolburg, H. & Mack, A. F. Comment on the topology of mammalian blood–cerebrospinal fluid barrier. Neurol. Psychiatry Brain Res. 20, 70–72 (2014).
Steffen, B. J., Breier, G., Butcher, E. C., Schulz, M. & Engelhardt, B. ICAM-1, VCAM-1, and MAdCAM-1 are expressed on choroid plexus epithelium but not endothelium and mediate binding of lymphocytes in vitro. Am. J. Pathol. 148, 1819–1838 (1996).
CAS PubMed PubMed Central Google Scholar
Kunis, G. et al. IFN-γ-dependent activation of the brain’s choroid plexus for CNS immune surveillance and repair. Brain 136, 3427–3440 (2013).
Kertser, A. et al. Corticosteroid signaling at the brain–immune interface impedes coping with severe psychological stress. Sci. Adv. 5, eaav4111 (2019).
Article CAS PubMed PubMed Central Google Scholar
Reboldi, A. et al. C–C chemokine receptor 6-regulated entry of TH-17 cells into the CNS through the choroid plexus is required for the initiation of EAE. Nat. Immunol. 10, 514–523 (2009).
Article CAS PubMed Google Scholar
Li, Z. et al. Blockade of VEGFR3 signaling leads to functional impairment of dural lymphatic vessels without affecting autoimmune neuroinflammation. Sci. Immunol. 8, eabq0375 (2023).
Article CAS PubMed Google Scholar
Howell, O. W. et al. Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis. Brain 134, 2755–2771 (2011).
Hsu, M. et al. Neuroinflammation creates an immune regulatory niche at the meningeal lymphatic vasculature near the cribriform plate. Nat. Immunol. 23, 581–593 (2022).
Article CAS PubMed PubMed Central Google Scholar
Dileepan, T. et al. Group A streptococcus intranasal infection promotes CNS infiltration by streptococcal-specific TH17 cells. J. Clin. Invest. 126, 303–317 (2016).
Comments (0)