Immunomodulatory Effects of Fractional CO2 Laser and Narrowband UVB in Stable Non-Segmental Vitiligo

Stable non-segmental vitiligo is sustained by persistent autoimmune responses involving tissue-resident memory T (TRM) cells, impaired regulatory T-cell (Treg) function, and chronic cytokine-mediated inflammation. Although fractional carbon dioxide (CO2) laser and narrowband ultraviolet B (NB-UVB) phototherapy are widely used to induce repigmentation, their immunomodulatory mechanisms remain incompletely understood. In this prospective, non-randomized exploratory study, 19 patients with stable non-segmental vitiligo received either monthly fractional CO2 laser monotherapy or fractional CO2 laser combined with NB-UVB phototherapy for 6 months. Serum IL-15 and IL-17A concentrations were quantified by ELISA at baseline, 3 months, and 6 months. Double immunofluorescence was performed to evaluate cutaneous TRM- and Treg-associated markers (CD4, CD8, CD25, CD49a, CD69, CD103, FOXP3) together with melanocyte-associated markers (MITF and c-KIT). Longitudinal differences between treatment groups were assessed using linear mixed-effects models with treatment-by-time interactions. Serum IL-15 and IL-17A concentrations decreased significantly over time in both treatment groups. At 6 months, IL-15 concentrations did not differ significantly from those in healthy controls in either group, whereas IL-17A concentrations did not differ significantly from healthy-control values in the fractional CO2 laser monotherapy group but remained significantly higher in the combination-treatment group. Cutaneous analyses demonstrated longitudinal changes in selected TRM- and Treg-associated markers and melanocyte-associated markers, with MITF showing the most pronounced increase. Several cutaneous immune markers remained significantly different from healthy-control values after 6 months. No statistically significant treatment-by-time interactions were detected for IL-15, IL-17A, or the evaluated dermal and epidermal markers. Fractional CO2 laser monotherapy and fractional CO2 laser combined with NB-UVB were both associated with longitudinal changes in circulating inflammatory cytokines and selected cutaneous immune- and melanocyte-associated markers in patients with stable non-segmental vitiligo. Persistent abnormalities in several cutaneous immune markers suggest that treatment did not fully restore the cutaneous immune-marker profile within the 6-month observation period. Given the small sample size and non-randomized exploratory design, the absence of statistically significant treatment-by-time interactions should not be interpreted as evidence of therapeutic equivalence, non-inferiority, or absence of an additional effect of NB-UVB.