Cell-type- and state-resolved transcriptomics uncovers distinct T cell and monocyte dysregulation in multiple sclerosis - PubMed
3 hours ago
- #Multiple sclerosis
- #Transcriptomics
- #Immune dysregulation
- The study uses cell-type- and state-resolved transcriptomics to analyze 1,075 transcriptomes from MS patients and healthy individuals across six immune cell-type-states.
- MS-associated transcriptional differences are more pronounced in unstimulated immune cells compared to stimulated ones, highlighting stable dysregulation.
- Shared and cell-type-specific transcriptional changes are identified, with key regulators like ZBTB16 prioritized across T cells and monocytes.
- A top T cell module is enriched for MS susceptibility genes and impacts proliferation, while a top monocyte module involves dysregulated TNF-α/NF-κB signaling.
- An in silico drug screen and in vitro validation suggest alvespimycin as a potential modulator for the dysregulated monocyte pathway.
- The findings offer potential diagnostic or prognostic biomarkers for MS in at-risk individuals based on peripheral immune signatures.