Single-cell transcriptomics reveals systemic immune dysregulation in non-segmental vitiligo.

Area of Science:

• Immunology
• Dermatology
• Genomics

Background:

• Non-segmental vitiligo (NSV) is an autoimmune disorder causing depigmented skin patches and significant psychosocial distress.
• While localized vitiligo mechanisms are studied, systemic immune cell involvement, particularly in peripheral blood mononuclear cells (PBMCs), is less understood.

Purpose of the Study:

• To investigate the single-cell transcriptional landscape of PBMCs in generalized, progressive non-segmental vitiligo (GP-NSV).
• To identify immune cell subset alterations and functional changes associated with active vitiligo.
• To uncover potential systemic immune dysregulation contributing to vitiligo pathogenesis.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) was performed on PBMCs from 3 untreated GP-NSV patients and 3 healthy controls.
• Flow cytometry validation was conducted on an additional cohort (7 GP-NSV patients, 30 controls).
• Computational analyses, including pseudotime trajectory and pathway enrichment, were used to analyze immune cell states.

Main Results:

• Significant heterogeneity in PBMC subsets was observed in vitiligo patients.
• Reduced KLRC2+ NK cells, enriched in TNF and apoptotic pathways, and decreased FCGR3A+ cytotoxic CD8+ T cells were noted.
• Increased STAM+ regulatory T cells (Tregs) and decreased EGR1+ B cells were found, with both subsets showing altered pathways related to osteoclast differentiation and calcium metabolism.

Conclusions:

• This study presents the first single-cell atlas of PBMCs in GP-NSV, revealing substantial immune cell alterations.
• Findings indicate profound systemic immune dysregulation in active vitiligo.
• The results provide a foundation for developing targeted therapeutic strategies for vitiligo.