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

TY - JOUR

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, Jörg

N1 - © 2022 The Author(s).

PY - 2023/1/1

Y1 - 2023/1/1

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.

U2 - 10.1016/j.isci.2022.105785

DO - 10.1016/j.isci.2022.105785

M3 - Article

C2 - 36594029

SN - 2589-0042

VL - 26

SP - 105785

JO - iScience

JF - iScience

IS - 1

ER -