Meta-Analysis of Alterations in Regulatory T Cells’ Frequency and Suppressive Capacity in Patients with Vitiligo

Abstract

Vitiligo is a noncontagious autoimmune skin depigmenting disease. Regulatory T cells (Tregs) play a key role in maintaining peripheral tolerance; however, Tregs' number, suppressive function, and associated suppressive molecules (FOXP3, IL-10, and TGF- β ) are found to be reduced in vitiligo patients. Although, the role of Tregs in vitiligo pathogenesis is well established, there are several contrary findings which suggest a controversial role of Tregs in vitiligo. Therefore, to clarify the role of Tregs in vitiligo pathogenesis, we aimed to study Tregs' frequency, suppressive capacity, and associated suppressive molecules (FOXP3, IL-10, and TGF- β ) in vitiligo patients through meta-analysis approach. A total of 30 studies involving 1223 vitiligo patients and 1109 controls were included in the study. Pooled results from our meta-analysis suggested significantly reduced Treg cells' frequency in vitiligo patients ( p = 0.002). Interestingly, Tregs' suppressive capacity was also significantly reduced in vitiligo patients ( p = 0.0002); specifically, Treg-mediated suppression of CD8 + T cells was impaired in vitiligo patients ( p < 0.00001). Moreover, FOXP3, a key Tregs' transcription factor, was significantly reduced in blood and skin of vitiligo patients ( p < 0.00001). Intriguingly, the FOXP3 expression was significantly reduced in the lesional skin as compared to perilesional and nonlesional skin ( p = 0.007 and p = 0.04). Furthermore, the expression of key Treg-associated suppressive cytokines IL-10 and TGF- β were significantly reduced in vitiligo patients ( p = 0.0005 and p = 0.01). The disease activity-based analysis suggested for reduced Tregs' frequency and FOXP3 expression in active vitiligo patients ( p = 0.05 and p = 0.01). We also studied the effect of microRNA-based treatment, narrow band–UVB phototherapy, and Treg-associated treatments on Tregs' frequency, FOXP3, and IL-10 expression. Interestingly, we found increased Tregs' frequency, FOXP3, and IL-10 expression after the treatment ( p = 0.007, p < 0.0001, and p = 0.002). Overall, our meta-analysis suggests that the Tregs play a crucial role in pathogenesis and progression of vitiligo, and hence, Treg-based therapeutic interventions could be effective in vitiligo patients.

Beyond skin white spots: Vitiligo and associated comorbidities

“…Third, regulatory T cells (Tregs) play a critical role in the augmentation of peripheral immune tolerance, thereby protecting the human body from autoimmune damage (45). Accumulating data suggests that patients with vitiligo have a reduced number of Tregs; decreased Treg suppression; and reduced levels of Treg-associated suppressive cytokines, such as interleukin (IL)-10 and transforming growth factor-β (46,47). Likewise, quantitative and functional deficiencies in Tregs have been reported in a variety of autoimmune diseases, including RA, SLE, type 1 diabetes mellitus, multiple sclerosis, and myasthenia gravis, among others, which might contribute to the elevated frequency of various associated autoimmune diseases in patients with vitiligo (48).…”

Topical ruxolitinib: A new treatment for vitiligo

“…25 Moreover, it would be useful to determine the effect of topical ruxolitinib on skin-resident T cells during and after the discontinuation of treatment, in order to evaluate possible changes in the micro-environment and their effects on recurrent disease. 59 In the case of post-discontinuation depigmentation, further cycles of ruxolitinib may help to control the disease but it is also necessary to consider the risks of further AEs, increased costs, and reduced patient compliance.…”

Increased Expression of Long Noncoding RNA LOC100506314 in T cells from Patients with Nonsegmental Vitiligo and Its Contribution to Vitiligo Pathogenesis

“…As expected, the expression of LOC100506314 was elevated CD4+ T cells from patients with vitiligo and associated the severity of vitiligo. In addition, regulatory T cells (Tregs) play a crucial role in the pathogenesis of vitiligo, and patients with vitiligo had decreased Tregs frequency and function [39][40][41]. Inhibition of STAT3 phosphorylation via LOC100506314 might facilitate the differentiation of Tregs [42].…”