Alteration in regulatory T cells and programmed cell death 1-expressing regulatory T cells in active generalized vitiligo and their clinical correlation

Tembhre, Manoj Kumar; Parihar, Anita Singh; Sharma, Vaishali; Sharma, Alpana; Chattopadhyay, Parthaprasad; Gupta, Somesh

doi:10.1111/bjd.13511

Cited by 57 publications

(61 citation statements)

References 55 publications

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“…They indicated that higher expression of Tim‐3 in patients with vitiligo may cause melanocytes destruction via Tim‐3/Gal‐9 involvement due to the alteration of peripheral cell‐mediated immunity . Later on, they revealed significant increasing of CD3 + /CD4 + /PD‐1 + and PD‐1 + Tregs in patients with vitiligo confirming the roles of these receptors in disease immunoregulation . In agreement with our study, up‐regulation of Tim‐3 mRNA has been reported in both CD4 + and CD8 + T cells of CNS‐resident cells during EAE .…”

Section: Discussionsupporting

confidence: 90%

See 1 more Smart Citation

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: 90%

“…Two studies by Tembhre et al. have studied the expression level of Tim‐3 and PD‐1 in patients with vitiligo . In their studies, more expression of Tim‐3 on peripheral CD4 + T cells has been reported in patients with generalized vitiligo.…”

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

Experimental Dermatology

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show abstract

“…In this issue of the BJD , the findings of Tembhre et al . support a role for Tregs in vitiligo pathogenesis.…”

mentioning

confidence: 79%

Programmed death 1 expressing regulatory T cells in vitiligo

Kemp

2015

Br J Dermatol

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“…Significant defects in the immunosuppressive function of CD4 + CD25 + Tregs in patients with vitiligo on CD4 + CD25 − T cells or CD8 + T cells have been shown by in vitro assays with TCR stimulation . In vitiligo skin, mRNA levels of molecules related to Treg function were decreased in Foxp3, CTLA‐4, TGF‐β, CCL21 (a ligand for chemokine receptor CCR7) and CCL22 (a ligand for CCR4) . Notably, GWAS using 4680 cases of vitiligo and 39 586 controls identified some associated loci related to immunoregulation, such as CTLA‐4, Eos (IKZF4) and CD80 (a binding partner of CTLA‐4 to inhibit T‐cell activation), indicating that a genetic background associated with Treg is involved in the pathogenesis of vitiligo.…”

Section: Vitiligomentioning

confidence: 99%