AT A GLANCE 

In a multi-modal study, researchers used transcriptomic and single-cell analysis to uncover elevated Th1, Th2, and Th17/Th22 immune activity not only in depigmented vitiligo lesions but also in clinically normal skin. The findings suggest early, systemic immune activation as a key feature of vitiligo pathogenesis, with implications for treatment timing and therapeutic targeting.

Vitiligo has long been framed as a Th1/IFN-γ–driven autoimmune condition, but new transcriptomic data show that its immune footprint is broader and more complex—spanning lesional and nonlesional skin. In this multi-modal study, researchers analyzed biopsies from 15 vitiligo patients and 14 healthy controls using bulk and single-cell RNA sequencing, PCR, and immunohistochemistry to map the cutaneous immune landscape.

Results showed a striking pattern of immune activation across both affected and unaffected skin in vitiligo patients. Lesional skin demonstrated heightened expression of Th1 markers (OASL, CXCL9, CXCL10), alongside signatures of Th2 (IL4, IL4R, CCL13, CCL17, CCL22, CCL26) and Th17/Th22 pathways (IL20, S100A7/A8/A9, PI3). Even nonlesional skin was immunologically active, with elevated cytokine and chemokine expression across all three T-helper axes. Several inflammatory markers, including IL25 and CXCL14, were strongly correlated with clinical severity scores. Single-cell RNA sequencing revealed Th2 cytokine IL13 expression in helper T cells from nonlesional skin and persistent IFNG signaling in lesional T cells—indicating that immune dysregulation precedes visible depigmentation. 

"Our findings show that immune dysregulation in vitiligo involves immune axes beyond Th1/Tc1, with upregulation of particularly type 2 markers already in nonlesional skin, suggesting a role during early lesion formation," write the authors.

Reference: Brunner PM, David E, Del Duca E, et al. Transcriptomic profiling of vitiligo patients shows polar immune dysregulation in involved and uninvolved skin. J Allergy Clin Immunol. Published online June 11, 2025. doi:10.1016/j.jaci.2025.06.002