Regulatory T‐cell cytokines in patients with nonsegmental vitiligo

Abstract

In the etiopathogenesis of vitiligo, the role of suppressor cytokines, such as transforming growth factor-β (TGF-β) and interleukin-10 (IL-10), associated with regulatory T-cells (Treg) is not completely known. In this study, the role of Treg-cell functions in the skin of patients with nonsegmental vitiligo was investigated. Lesional and nonlesional skin samples from 30 adult volunteers ranging in age from 18 to 36 years with nonsegmental vitiligo were compared with normal skin area excision specimens of 30 benign melanocytic nevus cases as controls. All samples were evaluated staining for forkhead box P3 (Foxp3), TGF-β, and IL-10 using the standardized streptavidin-biotin immunoperoxidase immunohistochemistry method. Foxp3 expression was lower in lesional vitiligo skin specimens compared to controls; it was also lower in lesional vitiligo specimens than nonlesional vitiligo specimens. IL-10 levels were lower in lesional vitiligo specimens compared to the controls, whereas IL-10 expression was significantly lower in lesional specimens compared with nonlesional specimens. TGF-β expression was higher in both lesional and nonlesional skin specimens of patients with vitiligo compared to controls. TGF-β expression was lower in lesional skin specimens than nonlesional skin specimens. In addition, there was no significant correlation between Foxp3 expression with TGF-β and IL-10 expressions in lesional skin specimens in the vitiligo group. In this study, results supporting the contribution of Treg cells and IL-10 deficiency to the autoimmune process were obtained. Therefore, future studies are necessary to demonstrate the definitive role of Treg-cell functions in the etiopathogenesis of vitiligo.

Decreased suppression of CD8+ and CD4+ T cells by peripheral regulatory T cells in generalized vitiligo due to reduced NFATC1 and FOXP3 proteins

“…Previously, significantly reduced IL-10 and TGF-β mRNA and protein levels were reported in serum/skin of GV patients. [16,32,[39][40][41][42][43][44] Moreover, the ratio of pro-inflammatory cytokine to anti-inflammatory cytokine was found to be altered in the in vitro suppression assay. In particular, significantly increased ratio of IFN-γ:IL-10 and IFN-γ:TGF-β was observed in Treg:CD8 + T cells and Treg:CD4 + T cells' co-culture systems of GV patients ( Figure S7a-d), suggesting the crucial role of IL-10 and TGF-β deficiency in compromised suppressive capacity of Treg cells in GV ( Figure S13).…”

Altered expression of nuclear factor of activated T cells, forkhead box P3, and immune‐suppressive genes in regulatory T cells of generalized vitiligo patients

“…Recently, Zhang et al () have reported reduced serum levels of sCTLA4, IL10, and TGFB in vitiligo patients. The role of IL‐10 in the pathogenesis of vitiligo has been evidenced by several studies demonstrating the reduced levels of IL‐10 in serum (Ala, Pasha, Rao, Komaravalli, & Jahan, ; Tembhre et al, ), in lesional skin (Kidir, Karabulut, Ercin, & Atasoy, ), and in Tregs (Zhang et al, ) of vitiligo patients as compared to controls. The present study also found decreased IL10 transcript in Tregs and decreased IL‐10 protein level in plasma of GV patients as compared to controls (Figure a,b).…”

Mechanisms of melanocyte death in vitiligo

“…Discrepancies between studies about counts of Tregs might be attributed to (1) each sampling reflects merely a cross‐section of a developing disease progression, thus the panorama of changing Treg counts can't be obtained; (2) many other activated CD4 + cells also express FoxP3 and FoxP3 antibodies employed in the experiment can also bind to them 204 ; (3) racial and age factors 194 . Several studies illustrated the notably decreased levels of TGF‐β 195,201,205 and IL‐10 205,206 in the serum of vitiligo patients in contrast to controls. FoxP3 expression in serum and lesional skin, 201 FoxP3 mRNA expression in lesional and perilesional skin declined in vitiligo patients 207 .…”