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

doi:10.1016/j.isci.2022.105785

Osteopontin associates with brain T_RM-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

Immunology

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Article number	105785
Journal	iScience
Volume	26
Issue number	1
DOIs	https://doi.org/10.1016/j.isci.2022.105785
Publication status	Published - 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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title = "Osteopontin associates with brain TRM-cell transcriptome and compartmentalization in donors with and without multiple sclerosis",

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.",

author = "Hsiao, {Cheng Chih} and Engelenburg, {Hendrik J.} and Aldo Jongejan and Jing Zhu and Baohong Zhang and Michael Mingueneau and Moerland, {Perry D.} and Inge Huitinga and Joost Smolders and J{\"o}rg Hamann",

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). {\textcopyright} 2022 The Author(s).",

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AU - Hsiao, Cheng Chih

AU - Engelenburg, Hendrik J.

AU - Jongejan, Aldo

AU - Zhu, Jing

AU - Zhang, Baohong

AU - Mingueneau, Michael

AU - Moerland, Perry D.

AU - Huitinga, Inge

AU - Smolders, Joost

AU - Hamann, Jörg

N1 - 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).

PY - 2023/1/20

Y1 - 2023/1/20

N2 - 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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Osteopontin associates with brain T_RM-cell transcriptome and compartmentalization in donors with and without multiple sclerosis

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