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; J. rg Hamann

doi:10.1016/j.isci.2022.105785

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^*
, J. rg Hamann^*

^*Corresponding author for this work

Netherlands Institute for Neuroscience
Amsterdam UMC
Biogen IDEC
University of Amsterdam
Erasmus MC

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

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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 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

Keywords

Molecular neuroscience
Neuroscience
Omics
Transcriptomics

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@article{c4310e0845494ea08b079d96bda4e197,

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.",

keywords = "Molecular neuroscience, Neuroscience, Omics, Transcriptomics",

author = "Cheng-Chih Hsiao 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 Hamann, \{J. rg\}",

note = "Funding Information: 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 ). Funding Information: 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. Publisher Copyright: {\textcopyright} 2022 The Author(s)",

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doi = "10.1016/j.isci.2022.105785",

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T1 - Osteopontin associates with brain TRM-cell transcriptome and compartmentalization in donors with and without multiple sclerosis

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, J. rg

N1 - Funding Information: 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 ). Funding Information: 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. Publisher Copyright: © 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.

AB - 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.

KW - Molecular neuroscience

KW - Neuroscience

KW - Omics

KW - Transcriptomics

UR - https://www.scopus.com/pages/publications/85144867231

UR - https://www.ncbi.nlm.nih.gov/pubmed/36594029

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SN - 2589-0042

VL - 26

JO - iScience

JF - iScience

IS - 1

M1 - 105785

ER -

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

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