Purpose: Vitiligo is a T cell-mediated skin depigmentation disease. Though treatments arresting disease progression and inducing repigmentation are available, the efficacy of these options is often limited and poorly sustained. How stromal signals contribute to the interferon-γ-dominant skin niches is unclear. This study aims to determine how fibroblasts participate in the IFN-γ-dominant vitiligo niche. Patients and methods: Mouse vitiligo models were established. Fibroblasts from control and vitiligo mice were extracted for RNA sequencing. In vitro IFN-γ stimulation was performed to verify the JAK-STAT pathway by qPCR and Western blot. T cell polarization with chemokines was measured by flow cytometry. Protein levels in tissues were also examined by IHC. Results: The vitiligo mouse model recapitulates the human CD8-IFN-γ pathway. RNA sequencing revealed elevated chemokine CCL2 and CCL8 in vitiligo fibroblast, which may be regulated by the JAK-STAT signaling. Such phenomenon is verified by JAK inhibitor peficitinib in vitro. Moreover, CCL2 addition into the naïve T polarization system promoted type 2 cytokines secretion, which represents a hallmark of vitiligo lesions. Conclusion: Dermal fibroblasts, a principal constituent of skin structure, respond to IFN-γ by skewing T cells towards a type 2 cytokine profile via CCL2 and CCL8, which can be abrogated by JAK inhibitor peficitinib.

This study aimed to investigate the potential biomarkers of vitiligo by evaluating the disease activity and curative effect of autologous cultured pure melanocyte transplantation (CMT) on patients. Altogether, 36patients with stable vitiligo were treated with CMT. Blister fluid samples were collected from patients with stable vitiligo. Patients with active vitiligo were matched with healthy controls. The chemokine levels in the serum and blister fluid samples were measured using Luminex. The curative effect on patients with stable vitiligo was evaluated 6 months after treatment. Treatment responses were defined according to the extent of repigmentation as effective (if 50% or more repigmentation was achieved) or ineffective (if less than 50% or worse repigmentation was achieved). Patients received re-transplantation if the initial treatment was ineffective. The levels of C-X-C motif chemokine ligand (CXCL)9 and CXCL10 in blister fluid samples were significantly lower in stable patients than in active participants. Receiver operating characteristic analysis revealed that the levels of CXCL9 and CXCL10 were sensitive and specific in diagnosing active vitiligo. Further, 65.6% (21/32) of patients who received CMT had effective treatment responses. The high CXCL9 level in the blister fluid was a significant predictor of ineffective treatment responses. The treatment response was significantly enhanced after treatment. Four patients with ineffective treatment responses received anti-inflammatory treatment and re-transplantation. The CXCL9 and CXCL10 levels in the blister fluid were related to the presence of active vitiligo. Also, the CXCL9 level was a predictor of the effectiveness of CMT in treating vitiligo.

Objective: To clarify the causal relationship between anxiety-depression and the progression and outcomes of vitiligo, providing a basis for enhancing psychological interventions in the treatment of vitiligo.Methods: A two-sample Mendelian randomization analysis was used to validate the causal relationship between anxiety, depression, and vitiligo. The Hospital Anxiety and Depression Scale (HADS) assessed the psychiatric condition of vitiligo patients. Fisher’s chi-square tests and rank sum tests analyzed the differences in clinical characteristics among vitiligo patients with different HADS scores. Regression analysis assessed the correlation between anxiety-depression and disease progression and treatment outcomes.Results: Mendelian randomization analysis showed that depression significantly increases the risk of vitiligo (OR = 4.46, 95% CI: 1.16–17.18, p = 0.03). According to the HADS scores, clinical characteristics differed significantly among the groups (p < 0.05). Univariate regression analysis demonstrated that both HADS (B = –1.168, p < 0.001, 95% CI: −1.532 to −0.804) and VIDA (B = –2.157, p < 0.001, 95% CI: −3.464 to −0.887) were significantly negative associated factors for disease outcomes. However, HADS (B = –1.006, p < 0.001, 95% CI: −1.475 to −0.657) emerged as the only factor influencing therapeutic efficacy in multivariate regression analysis. A restricted cubic spline graph illustrates a U-shaped relationship between HADS and clinical efficacy, with the most significant impact on therapeutic efficacy occurring when HADS equals 15.Conclusion: Anxiety—depression exhibit a bidirectional positive causal relationship with vitiligo. Moderate to severe anxiety-depression significantly influences the clinical efficacy of vitiligo treatment.