Cytokines: the yin and yang of vitiligo pathogenesis

Singh, Mala; Kotnis, Ashwin; Jadeja, Shahnawaz D.; Mondal, Anushree; Mansuri, Mohmmad Shoab

doi:10.1080/1744666x.2019.1550358

Cited by 32 publications

(41 citation statements)

References 146 publications

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“…As a result, the expression of PD‐1 was increased to regulate the activation of T cells . Similar to other autoimmune diseases, disequilibrium between pro‐ and anti‐inflammatory cytokines has been demonstrated in vitiligo pathogenesis . In the present study, significant higher secretion of IFN‐γ and TNF‐α and lower production of IL‐4 were shown in stimulated PBMCs of patients with vitiligo compared with healthy controls.…”

Section: Discussionsupporting

confidence: 69%

Expression analysis of PD‐1 and Tim‐3 immune checkpoint receptors in patients with vitiligo; positive association with disease activity

Rahimi

Hossein-Nataj

Hajheydari

et al. 2019

Experimental Dermatology

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The contribution of immune checkpoint receptors in the immunopathogenesis of various autoimmune diseases has been addressed in previous reports. In this study, the expression profile of T‐cell immunoglobulin and mucin‐domain containing‐3 (Tim‐3) and programmed cell death‐1 (PD‐1) checkpoint molecules was investigated in CD8+ T cells of Vitiligo patients. The association of Tim‐3 and PD‐1 expression with disease activity was also explored. The frequency of Tim‐3+/PD‐1+/CD8+ T cells in 30 patients with vitiligo and 30 sex‐ and age‐matched controls was determined by flow cytometry. CD8+ T cells were then positively isolated by magnetic beads, and the mRNA expression of PD‐1 and Tim‐3 was determined by TaqMan‐based real‐time PCR. To measure the cytokines production, PBMCs were stimulated with PMA/ionomycin and concentrations of IL‐4, IFN‐γ and TNF‐α were measured in culture supernatants by ELISA. Disease activity of patients with vitiligo was determined using the Vitiligo Area Severity Index. Patients with vitiligo have significantly shown more expression of Tim‐3 and PD‐1 on their CD8+ T cells compared with controls. Expression analysis of Tim‐3 mRNA, but not PD‐1, confirmed the results obtained from flow cytometry. While the production levels of TNF‐α and IFN‐γ were found higher by patients with vitiligo, IL‐4 production was lower in patients compared with controls. A direct association was observed between the Tim‐3 and PD‐1 expression and also the production of pro‐inflammatory cytokines with disease activity of patients with vitiligo. Our results indicate that Tim‐3 and PD‐1 are involved in immune dysregulation mechanisms of CD8+ T cells in vitiligo and may introduce as potential biomarkers for disease progression and targeted immunotherapy.

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Section: Discussionsupporting

confidence: 69%

Expression analysis of PD‐1 and Tim‐3 immune checkpoint receptors in patients with vitiligo; positive association with disease activity

Rahimi

Hossein-Nataj

Hajheydari

et al. 2019

Experimental Dermatology

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“…Vitiligo is a common autoimmune hypo-pigmentary skin disorder, caused by selective destruction of melanocytes (28). Recent study demonstrated enhanced Th17 response in peripheral blood of patients with vitiligo (5).…”

Section: Discussionmentioning

confidence: 99%

“…TYR and TRP-1 are critical for the synthesis of melanin, the loss of which contributes to the development of vitiligo (32). Recent study has shown that cytokine imbalance in systemic and skin microenvironments is closely associated with melanocyte biology and vitiligo pathogenesis (28). IL-6 secreted by adjacent keratinocytes in epidermal melanin unit inhibits the growth and proliferation of melanocytes in a paracrine manner (33).…”

Section: Discussionmentioning

confidence: 99%

Critical role of metabotropic glutamate receptor 4 in bone marrow-derived dendritic cells in the Th17 cell differentiation and the melanogenesis of B16 cells

Zhao

Zhou

Liu

et al. 2020

Braz J Med Biol Res

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Vitiligo is an acquired pigmentary disorder resulting from selective destruction of melanocytes. Emerging studies have suggested that T helper cell 17 (Th17) is potentially implicated in vitiligo development and progression. It was recently discovered that metabotropic glutamate receptor 4 (mGluR4) can modulate Th17-mediated adaptive immunity. However, the influence of mGluR4 on melanogenesis of melanocytes has yet to be elucidated. In the present study, we primarily cultured mouse bone marrow-derived dendritic cells (BMDC) and then knocked down and over-expressed mGluR4 using transfection. Transduced BMDC were co-cultured with CD4 + T cells and the expression of Th17-related cytokines were measured. The morphology and melanogenesis of B16 cells were observed after being treated with co-culture medium of CD4 + T cells and transduced BMDC. We found that mGluR4 knockdown did not affect the co-stimulatory CD80 and CD86 upregulation after lipopolysaccharide stimulation but did increase the expression of Th17-related cytokines, and further down-regulated the expression of microphthalmia-associated transcription factor (MITF) and the downstream genes, decreased melanin production, and destroyed the morphology of B16 cells. Conversely, over-expression of mGluR4 reduced the expression of CD80 and CD86, suppressed the production of Th17-related cytokines, increased the expression of MITF, and did not destroy the morphology of B16 cells. Our study confirmed that mGluR4 modulated the Th17 cell polarization and resulted in the alteration of melanogenesis and morphology of B16 cells. Collectively, these findings suggest mGluR4 might be a potent target involved in the immune pathogenesis of vitiligo.

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“…In this complex autoimmune process, IL-10, though anti-inflammatory by nature, is known to play a pathogenic role in the development of the vitiligo. 44,45 IL-13, a Th2 anti-inflammatory cytokine, which was once believed to have a significant role in allergy, is now known to mediate anti-inflammatory processes in susceptibility and progression of various autoimmune diseases. 46 Previous studies have demonstrated increased expression of inflammatory cytokines in skin and circulation among vitiligo patients.…”

Section: Discussionmentioning

confidence: 99%

Lack of association of IL-10 (rs1800896) and IL-13 (rs1800925) with non-segmental vitiligo susceptibility in South Indian population

Rajendiran

Rajappa

Chandrashekar

et al. 2020

Indian J Dermatol Venereol Leprol

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Background:Vitiligo is an autoimmune depigmentation disorder caused by multiple etiologies. Genetic polymorphisms in cytokine genes influence their expression and augment disease development. Analyzing the influence of genetic polymorphisms will help in better understanding of the complex etiopathogenesis of vitiligo. Aim: To study the influence of interleukin IL-10 (rs1800896) and IL-13 (rs1800925) polymorphisms on vitiligo risk in South Indian population. Methods: Two hundred and sixty-four vitiligo patients and 264 controls were recruited in this study. Genotyping was done by quantitative PCR and plasma cytokine levels were measured by ELISA. Results: Allele frequencies of IL-10 (rs1800896) and IL-13 (rs1800925) SNPs were observed to be equal in the groups. Mutant allele G of IL-10 (rs1800896) enhanced the familial inheritance of vitiligo (P < 0.0001, OR-25.1, 95% CI-7.64-82.7) and influenced the development of vulgaris type of vitiligo (P = 0.034, OR-1.83, 95% CI-1.07-3.13). Ancestral allele A of IL-10 (rs1800896) conferred protection against development of acrofacial vitiligo (P = 0.04, OR-0.56, 95% CI-0.33-0.95). Circulatory IL-10 levels in vitiligo patients were higher than controls (P < 0.0001). Individuals with genotype GG of IL-10 (rs1800896) had the highest circulatory levels of IL-10 (P < 0.0001). Among the genotypes of IL-13 (rs1800925) variant, none influenced the phenotype of nonsegmental vitiligo such as gender, family history, age of onset and types of vitiligo (P > 0.05). In addition, no difference was noted in the circulatory levels of IL-13 between patients and controls (P = 0.48). Within patients, CC genotype of IL-13 (rs1800925) was observed to enhance the circulatory IL-13 levels (P < 0.0001). Limitation: Replication group analysis in a larger multicentric cohort in future would validate further understanding of vitiligo susceptibility in South Indian ethnics. Conclusion: IL-10 (rs1800896) and IL-13 (rs1800925) polymorphisms did not confer risk to develop vitiligo in South Indian population.

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Cytokines: the yin and yang of vitiligo pathogenesis

Cited by 32 publications

References 146 publications

Expression analysis of PD‐1 and Tim‐3 immune checkpoint receptors in patients with vitiligo; positive association with disease activity

Expression analysis of PD‐1 and Tim‐3 immune checkpoint receptors in patients with vitiligo; positive association with disease activity

Critical role of metabotropic glutamate receptor 4 in bone marrow-derived dendritic cells in the Th17 cell differentiation and the melanogenesis of B16 cells

Lack of association of IL-10 (rs1800896) and IL-13 (rs1800925) with non-segmental vitiligo susceptibility in South Indian population

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