Osteopontin associates with brain T RM -cell transcriptome and compartmentalization in donors with and without multiple sclerosis.

Autor: Hsiao CC; Neuroimmunology Research Group, Netherlands Institute for Neuroscience, 1105 BA Amsterdam, the Netherlands.; Department of Experimental Immunology, Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Centers, 1105 AZ Amsterdam, the Netherlands., Engelenburg HJ; Neuroimmunology Research Group, Netherlands Institute for Neuroscience, 1105 BA Amsterdam, the Netherlands., Jongejan A; Bioinformatics Laboratory, Department of Epidemiology and Data Science, Amsterdam University Medical Centers, 1105 AZ Amsterdam, the Netherlands., Zhu J; Translational Biology, Biogen, Cambridge, MA 02142, USA., Zhang B; Translational Biology, Biogen, Cambridge, MA 02142, USA., Mingueneau M; Multiple Sclerosis and Neurorepair Research Unit, Biogen, Cambridge, MA 02142, USA., Moerland PD; Bioinformatics Laboratory, Department of Epidemiology and Data Science, Amsterdam University Medical Centers, 1105 AZ Amsterdam, the Netherlands., Huitinga I; Neuroimmunology Research Group, Netherlands Institute for Neuroscience, 1105 BA Amsterdam, the Netherlands.; Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, 1098 XH Amsterdam, the Netherlands., Smolders J; Neuroimmunology Research Group, Netherlands Institute for Neuroscience, 1105 BA Amsterdam, the Netherlands.; MS Center ErasMS, Departments of Neurology and Immunology, Erasmus Medical Center, 3015 GD Rotterdam, the Netherlands., Hamann J; Neuroimmunology Research Group, Netherlands Institute for Neuroscience, 1105 BA Amsterdam, the Netherlands.; Department of Experimental Immunology, Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Centers, 1105 AZ Amsterdam, the Netherlands.
Jazyk: angličtina
Zdroj: IScience [iScience] 2022 Dec 09; Vol. 26 (1), pp. 105785. Date of Electronic Publication: 2022 Dec 09 (Print Publication: 2023).
DOI: 10.1016/j.isci.2022.105785
Abstrakt: The human brain is populated by perivascular T cells with a tissue-resident memory T (T RM )-cell phenotype, which in multiple sclerosis (MS) associate with lesions. We investigated the transcriptional and functional profile of freshly isolated T cells from white and gray matter. RNA sequencing of CD8 + and CD4 + CD69 + T cells revealed T RM -cell signatures. Notably, gene expression hardly differed between lesional and normal-appearing white matter T cells in MS brains. Genes up-regulated in brain T RM cells were MS4A1 (CD20) and SPP1 (osteopontin, OPN). OPN is also abundantly expressed by microglia and has been shown to inhibit T cell activity. In line with their parenchymal localization and the increased presence of OPN in active MS lesions, we noticed a reduced production of inflammatory cytokines IL-2, TNF, and IFNγ by lesion-derived CD8 + and CD4 + T cells ex vivo . Our study reports traits of brain T RM cells and reveals their tight control in MS lesions.
Competing Interests: C.C.H., J.H.E., A.J., and P.D.M. declare that they have no competing interests. I.H., J.S., and J.H. obtained financial support from Biogen for conducting this study. J.Z., B.Z., and M.M. are employees of Biogen and hold stocks from the company.
(© 2022 The Author(s).)
Databáze: MEDLINE
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