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*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Article number105785
JournaliScience
Volume26
Issue number1
DOIs
Publication statusPublished - 20 Jan 2023

Bibliographical note

Acknowledgments
We are grateful to the brain donors and their families for their commitment to the Netherlands Brain Bank donor program. Funding for this research was obtained from Biogen, the German Research Foundation (FOR 2149), and the Nationaal MS Fonds (OZ2018-003).

© 2022 The Author(s).

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