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, 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/inward/record.uri?partnerID=HzOxMe3b&scp=85144867231&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/36594029
U2 - https://doi.org/10.1016/j.isci.2022.105785
DO - https://doi.org/10.1016/j.isci.2022.105785
M3 - Article
C2 - 36594029
SN - 2589-0042
VL - 26
JO - iScience
JF - iScience
IS - 1
M1 - 105785
ER -