Osteopontin associates with brain TRM-cell transcriptome and compartmentalization in donors with and without multiple sclerosis
Cheng-Chih Hsiao,
Hendrik J. Engelenburg,
Aldo Jongejan,
Jing Zhu,
Baohong Zhang,
Michael Mingueneau,
Perry D. Moerland,
Inge Huitinga,
Joost Smolders,
Jörg Hamann
Affiliations
Cheng-Chih Hsiao
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; Corresponding author
Hendrik J. Engelenburg
Neuroimmunology Research Group, Netherlands Institute for Neuroscience, 1105 BA Amsterdam, the Netherlands
Aldo Jongejan
Bioinformatics Laboratory, Department of Epidemiology and Data Science, Amsterdam University Medical Centers, 1105 AZ Amsterdam, the Netherlands
Jing Zhu
Translational Biology, Biogen, Cambridge, MA 02142, USA
Baohong Zhang
Translational Biology, Biogen, Cambridge, MA 02142, USA
Michael Mingueneau
Multiple Sclerosis and Neurorepair Research Unit, Biogen, Cambridge, MA 02142, USA
Perry D. Moerland
Bioinformatics Laboratory, Department of Epidemiology and Data Science, Amsterdam University Medical Centers, 1105 AZ Amsterdam, the Netherlands
Inge Huitinga
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
Joost Smolders
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; Corresponding author
Jörg Hamann
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; Corresponding author
Summary: The human brain is populated by perivascular T cells with a tissue-resident memory T (TRM)-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 TRM-cell signatures. Notably, gene expression hardly differed between lesional and normal-appearing white matter T cells in MS brains. Genes up-regulated in brain TRM 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 TRM cells and reveals their tight control in MS lesions.
