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Published on: June 13, 2011
Peripheral CD4 T-Cell State Remodeling in Migraine Revealed by Single-Cell RNA Sequencing
Quan Feng1, Yichen Li1, Na Li1
1Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chongqing, 400016, China.
None:
Migraine may involve neuroimmune-related mechanisms, but migraine-associated peripheral immune-cell states remain incompletely defined. We aimed to characterize peripheral blood immune remodeling in migraine at single-cell resolution. We reanalyzed PBMC single-cell RNA-sequencing dataset GSE269117, using migraine and vestibular migraine samples as the migraine group and healthy controls as controls. After quality control, we performed major immune-cell annotation, CD4 T-cell subclustering, pseudobulk differential-expression analysis, pathway enrichment, pseudotime reconstruction, CellChat-based communication analysis, transcription-factor activity inference and AL589693.1-focused state analysis. A total of 31,514 PBMCs from 15 retained biological samples were analyzed and annotated into six major immune-cell populations. Major lineage proportions showed no broad sample-level differences between groups, whereas sample-level analysis of 7,647 CD4 T cells indicated a redistribution of CD4 T-cell states. At the sample level, migraine samples showed enrichment of non-cytotoxic-like CD4 T cells and depletion of cytotoxic-like CD4 T cells compared with controls. CD4 pseudobulk and enrichment analyses highlighted inflammatory, estrogen-response, calcium-responsive and cAMP-related programs, with relative depletion of oxidative phosphorylation, MYC targets and translation-related pathways. Pseudotime analysis supported a shift toward earlier or less cytotoxic CD4 states. CellChat inferred fewer total interactions in migraine than in controls, especially cytotoxic-like CD4-related interactions. AL589693.1 emerged as a migraine-associated transcript, and its no-self signature marked a non-cytotoxic-skewed CD4 state that partially contributed to the CD4 imbalance. Peripheral CD4 T-cell state remodeling may represent an important feature of migraine-associated immune alterations, with AL589693.1-positive CD4 states as candidate markers for future validation.