Regulatory T cells in autoimmune skin diseases

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.

Section: Discussionmentioning

confidence: 99%

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

“…Accordingly, they suggested that ST18 gene may increase susceptibility to PV among the selected population . ST18 gene encodes a zinc‐finger DNA‐binding protein which is involved in apoptosis, inflammation regulation, as well as regulatory T cells, as two processes which are involved in PV pathogenesis . In another study on Chinese population, no association was reported between ST18 gene and PV, more in favour of population‐specific manner susceptibility hypothesis .…”

Section: Introductionmentioning

confidence: 99%

“…[10] ST18 gene encodes a zinc-finger DNA-binding protein which is involved in apoptosis, inflammation regulation, [11] as well as regulatory T cells, as two processes which are involved in PV pathogenesis. [12][13][14] In another study on Chinese population, no association was reported between ST18 gene and PV, more in favour of population-specific manner susceptibility hypothesis. [15] Recently, PV-associated variants within ST18 promoter region were discovered to increase ST18 transcription which subsequently induced inflammatory cytokines and contributed to PV pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

The association betweenST18 gene polymorphism and severe pemphigus disease among Iranian population

Etesami

Hassan

Ghandi

et al. 2018

Recently, ST18 polymorphism has played a role in increasing the risk of pemphigus among some populations such as Egyptian and Jewish. In addition, a variant within the ST18 promoter gene was shown to induce ST18 upregulation and cytokine secretion leading to keratinocyte susceptibility to anti-desmoglein antibodies. Thus, the present study aimed to assess the ST18 single nucleotide polymorphisms (SNP) relationship with pemphigus, disease severity and family history among Iranian population. A total of 111 pemphigus patients and 201 healthy controls were genotyped for three ST18 SNPs rs2304365, rs10504140 and rs4074067 by using TETRA-ARMS PCR method. The results indicated that risk allele A in rs2304365 was significantly higher in pemphigus patients, compared with the amount in the control group (OR = 2.43 CI = 1.49-3.975, P < 0.001). Thus, A allele represents a risk factor for pemphigus. Further, the patients carrying the risk allele had a more severe disease and a higher age of disease onset while no relationship was observed between the number of relapses and positive family history of pemphigus with the risk allele. Finally, dominant model was regarded as the strongest inheritance model for the associated risk. The present study confirmed the relationship between ST18 gene with pemphigus disease, a more severe disease, and a higher age of disease onset.

“…The exact mechanism of action of the immune‐modulating effect in DPCP is unclear, but to date it is generally assumed that it acts on different pathways to inhibit inflammation in alopecic areas which is achieved mainly by suppression of inflammatory cells, such as CD4+ and CD8+ T cells, restoration of equilibrium between Th1 and Th2 responses, or involvement of regulatory T cells . In our study, post‐treatment levels of serum Th1 type cytokines IFN‐γ and IL‐12 were significantly decreased, and levels of serum Th2 type cytokines IL‐4 and IL‐10 were increased in the responder group, which was different from the non‐responder group.…”

Section: Discussionmentioning

confidence: 48%

Serum level of IL‐4 predicts response to topical immunotherapy with diphenylcyclopropenone in alopecia areata

Gong

Zhang

et al. 2018

Potentially, elevated pre-treatment serum levels of IL-4 and IL-12 can be used as unfavorable and favorable predictors of DPCP therapeutic effect, respectively. In addition, pre-treatment elevated serum total IgE may predict increased risk for severe adverse side-effects to DPCP application. Whether serum cytokine expression levels can be used as predictors of response to other forms of treatment is unknown, but it may warrant investigation in the development of personalized treatments for AA.