Osteopontin associates with brain TRM-cell transcriptome and compartmentalization in donors with and without multiple sclerosis

• Published in: iScience Vol. 26; no. 1; p. 105785
• Main Authors: Hsiao, Cheng-Chih, Engelenburg, Hendrik J., Jongejan, Aldo, Zhu, Jing, Zhang, Baohong, Mingueneau, Michael, Moerland, Perry D., Huitinga, Inge, Smolders, Joost, Hamann, Jörg
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 20-01-2023; Elsevier
• Subjects: Molecular neuroscience; Neuroscience; Omics; Transcriptomics; Molecular neuroscience; Neuroscience; Transcriptomics; Omics
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2022.105785

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.
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•Human brain T cells possess a TRM-cell phenotypic and transcriptional profile•Human brain TRM cells are characterized by CD20 and osteopontin expression•In MS lesional T cells, the brain TRM-cell transcriptome is preserved•MS lesional TRM cells produce less inflammatory cytokines on stimulation
Neuroscience; Molecular neuroscience; Omics; Transcriptomics.