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| Status |
Public on Dec 05, 2022 |
| Title |
Transcriptional profiling of brain CD4+ and CD8+ TRM cells reveals dominant presence in white and grey matter in Multiple Sclerosis (MS) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The human brain is populated by perivascular CD8+ and CD4+ T cells with a tissue-resident memory T (TRM)-cell phenotype. In multiple sclerosis (MS), these cells associate with white matter (WM) and, to a lesser extent, grey matter (GM) lesions. We here investigated the transcriptional and functional profile of brain-resident T cells. Of n=11 subsequent post-mortem brain donors, we isolated CD8+ and CD4+ effector memory and effector memory re-expressing CD45RA T cells from blood and CD8+ and CD4+ CD69+ T cells from corpus callosum WM and cortical GM. Additionally, brain CD69+ T cells were sorted from subcortical WM, corpus callosum WM, and medulla WM/GM of n=3–5 brain donors as well as from paired normal-appearing WM and GM and from WM and GM lesions of n=6 MS brain donors. In all donors, WM and GM T cells were overwhelmingly CD69+CD103+/-. Bulk RNA sequencing of CD8+ and CD4+ CD69+ T cells revealed TRM-cell signatures, as marked by differential expression of, among others, SELL (CD62L), ITGA1 (CD49a), and S1PR1. Notably, gene expression hardly differed between lesional and normal-appearing WM CD8+ and CD4+ CD69+ 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 the increased presence of OPN in active MS lesions, we noticed a reduced production of the inflammatory cytokines IL-2, TNF, and IFNγ by MS lesion-derived CD8+ and CD4+ T cells ex vivo. This study discloses essential characteristics of human brain CD8+ and CD4+ TRM cells in non-MS and MS post-mortem WM and GM, reports OPN as a generic product of brain-resident immune cells, and shows a tight control of the activation state of TRM cells in MS lesions.
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| Overall design |
Comparative gene expression profiling analysis of bulk RNA-seq data of brain CD8+ and CD4+ CD69+ T cells from paired normal-appearing WM and GM and from WM and GM lesions of n=6 MS brain donors. Third dataset of 3.
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| Contributor(s) |
Hsiao C, Engelenburg HJ, Jongejan A, Zhu J, Zhang B, Mingueneau M, Moerland PD, Huitinga I, Smolders J, Hamann J |
| Citation(s) |
36594029 |
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| Submission date |
Oct 18, 2022 |
| Last update date |
Jan 13, 2023 |
| Contact name |
Jeen Engelenburg |
| E-mail(s) |
[email protected]
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| Organization name |
Netherlands Institute for Neuroscience
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| Lab |
Neuroimmunology lab
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| Street address |
Meibergdreef 47
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| City |
Amsterdam |
| ZIP/Postal code |
1105BA |
| Country |
Netherlands |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (34)
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| GSM6656438 |
NAWM, CD8, 01 |
| GSM6656439 |
NAGM, CD8, 01 |
| GSM6656440 |
WM_Lesion, CD8, 01 |
| GSM6656441 |
NAWM, CD4, 02 |
| GSM6656442 |
NAGM, CD4, 02 |
| GSM6656443 |
WM_Lesion, CD4, 02 |
| GSM6656444 |
NAWM, CD8, 02 |
| GSM6656445 |
NAGM, CD8, 02 |
| GSM6656446 |
WM_Lesion, CD8, 02 |
| GSM6656447 |
NAWM, CD4, 03 |
| GSM6656448 |
NAWM, CD8, 03 |
| GSM6656449 |
NAWM, CD4, 04 |
| GSM6656450 |
NAWM, CD8, 04 |
| GSM6656451 |
NAGM, CD8, 04 |
| GSM6656452 |
WM_Lesion, CD8, 04 |
| GSM6656453 |
NAWM, CD4, 05 |
| GSM6656454 |
NAGM, CD4, 05 |
| GSM6656455 |
WM_Lesion, CD4, 05 |
| GSM6656456 |
GM_Lesion, CD4, 05 |
| GSM6656457 |
NAWM, CD8, 05 |
| GSM6656458 |
NAGM, CD8, 05 |
| GSM6656459 |
WM_Lesion, CD8, 05 |
| GSM6656460 |
GM_Lesion, CD8, 05 |
| GSM6656461 |
NAWM, CD4, 06 |
| GSM6656462 |
NAGM, CD4, 06 |
| GSM6656463 |
WM_Lesion, CD4, 06 |
| GSM6656464 |
GM_Lesion, CD4, 06 |
| GSM6656465 |
NAWM, CD8, 06 |
| GSM6656466 |
NAGM, CD8, 06 |
| GSM6656467 |
WM_Lesion, CD8, 06 |
| GSM6656468 |
GM_Lesion, CD8, 06 |
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| This SubSeries is part of SuperSeries: |
| GSE216030 |
Transcriptional profiling of brain CD4+ and CD8+ TRM cells reveals dominant presence in white and grey matter in Multiple Sclerosis |
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| Relations |
| BioProject |
PRJNA891738 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE216028_allCounts.orig.tab.geo.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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