Cell-type- and state-resolved transcriptomics uncovers distinct T cell and monocyte dysregulation in multiple sclerosis
Abstract
Multiple sclerosis (MS) is a complex immune-mediated disorder with polygenic and multicellular underpinnings, necessitating cell-type-specific molecular studies to delineate dysregulated pathways. Here, we profile 1,075 transcriptomes from 167 patients with MS and 42 healthy participants across six peripheral immune cell-type-states. MS-associated transcriptional differences are more pronounced in primary (unstimulated) immune cells than in in vitro-stimulated counterparts. We identify shared and cell-type-specific transcriptional alterations at the level of genes, pathways, and co-expressed gene modules, prioritizing regulators, such as ZBTB16, across T cells and monocytes, and replicating six MS-associated modules in independent datasets. The top T cell module is enriched for MS susceptibility genes and affects proliferation. The top monocyte module implicates dysregulated TNF-α/NF-κB signaling, for which an in silico drug screen and in vitro validation nominate alvespimycin as a candidate modulator. Together, these findings define stable peripheral immune dysregulation signatures in MS that may serve as diagnostic or prognostic biomarkers in at-risk individuals.
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BibTeX
@article{roostaei2026celltype,
title = {{Cell-type- and state-resolved transcriptomics uncovers distinct T cell and monocyte dysregulation in multiple sclerosis}},
author = {Tina Roostaei and Masashi Fujita and Hanane Touil and Pia Kivisäkk and Cristin Mccabe and Parham Nejad and Afsana Sabrin and Frankie Garcia and Christiaan van Dorp and Daniel Felsky and Ioannis Vlachos and Daniel Hui and Jennifer Fransson and Will Macnair and Anna Williams and Lili Zhang and Wen Zhu and Zongqi Xia and Violetta Zujovic and Nikolaos Patsopoulos and Andrew Yates and Vijay Kuchroo and Tanuja Chitnis and Howard Weiner and Hans-Ulrich Klein and Philip de Jager},
journal = {Cell Reports},
year = {2026},
month = sep,
doi = {10.1016/j.celrep.2026.117417},
url = {https://hal.science/hal-05772384v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Cell-type- and state-resolved transcriptomics uncovers distinct T cell and monocyte dysregulation in multiple sclerosis
AU - Tina Roostaei
AU - Masashi Fujita
AU - Hanane Touil
AU - Pia Kivisäkk
AU - Cristin Mccabe
AU - Parham Nejad
AU - Afsana Sabrin
AU - Frankie Garcia
AU - Christiaan van Dorp
AU - Daniel Felsky
AU - Ioannis Vlachos
AU - Daniel Hui
AU - Jennifer Fransson
AU - Will Macnair
AU - Anna Williams
AU - Lili Zhang
AU - Wen Zhu
AU - Zongqi Xia
AU - Violetta Zujovic
AU - Nikolaos Patsopoulos
AU - Andrew Yates
AU - Vijay Kuchroo
AU - Tanuja Chitnis
AU - Howard Weiner
AU - Hans-Ulrich Klein
AU - Philip de Jager
PY - 2026
DA - 2026/09/30
JO - Cell Reports
DO - 10.1016/j.celrep.2026.117417
UR - https://hal.science/hal-05772384v1
AB - Multiple sclerosis (MS) is a complex immune-mediated disorder with polygenic and multicellular underpinnings, necessitating cell-type-specific molecular studies to delineate dysregulated pathways. Here, we profile 1,075 transcriptomes from 167 patients with MS and 42 healthy participants across six peripheral immune cell-type-states. MS-associated transcriptional differences are more pronounced in primary (unstimulated) immune cells than in in vitro-stimulated counterparts. We identify shared and cell-type-specific transcriptional alterations at the level of genes, pathways, and co-expressed gene modules, prioritizing regulators, such as ZBTB16, across T cells and monocytes, and replicating six MS-associated modules in independent datasets. The top T cell module is enriched for MS susceptibility genes and affects proliferation. The top monocyte module implicates dysregulated TNF-α/NF-κB signaling, for which an in silico drug screen and in vitro validation nominate alvespimycin as a candidate modulator. Together, these findings define stable peripheral immune dysregulation signatures in MS that may serve as diagnostic or prognostic biomarkers in at-risk individuals.
SN - 2211-1247
SN - 2211-1247
ER -