Transforming Growth Factor-β1 in the Skin and Serum of Patients with Non-segmental Vitiligo

Ghanem, Bothaina Mahrous; Sallam, Manar; El-Hawary, Amira Kamal; EL-Tantawy, Dina; Ahmed, Rehab-Allah; Darwish, Mohamed

doi:10.3923/ajd.2017.1.6

Cited by 3 publications

(5 citation statements)

References 24 publications

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“…Interestingly, the meta-analysis suggested significant decrease in TGF- β levels in vitiligo patients ( Figure 4(b) ). These results corroborate with the previous studies [ 5 , 20 – 22 , 28 , 29 , 31 , 32 ]; however, these results contrast with few reports [ 24 , 36 , 37 ]. The contrasting results may be due to differences in sample size and methodology used for TGF- β detection, i.e., differences in ELISA kits with varying sensitivities and differences in antibodies used for detection of TGF- β .…”

Section: Discussionsupporting

confidence: 92%

“…Although the previous studies strongly suggest the key role of Treg cells in vitiligo pathogenesis [8,14,[17][18][19][20][21], the role of Tregs in vitiligo patients' peripheral immunological tolerance is still being contested, as few findings suggest increased or unaltered Treg cells' frequency [33][34][35], Tregs' suppressive function [14], FOXP3 [14,33], and TGF-β [24,36,37] expression in vitiligo patients. Therefore, to overcome such contradiction, our current meta-analysis assessed the role of Treg cells in vitiligo pathogenesis by (i) investigating Treg cells' frequency in vitiligo patients; (ii) assessing Treg cells' suppressive capacity in vitiligo patients; (iii) determining FOXP3 expression levels in blood and skin of vitiligo patients; (iv) determining the expression levels of Tregs' suppressive cytokines: IL-10 and TGF-β in blood and skin of vitiligo patients; (v) carrying out disease activity-based analysis for Treg cells' frequency, FOXP3, IL-10, and TGF-β expression in vitiligo patients; and (vi) evaluating the effect of different therapeutic interventions on Treg cells' frequency, FOXP3, and IL-10 expression in vitiligo mice model and vitiligo patients through metaanalysis.…”

Section: Introductionmentioning

confidence: 99%

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

Giri

Mistry

Dwivedi

2022

Journal of Immunology Research

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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.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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

Giri

Mistry

Dwivedi

2022

Journal of Immunology Research

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“…Interestingly, we found significant decrease in IL‐10 levels between active and stable GV patients' Tregs, before and after calcium treatment; however, there was no significant difference found for TGF‐β levels between active and stable GV patients, suggesting that IL‐10 might play a crucial role in the disease activity. A previous study also reported that TGF‐β levels did not differ between active and stable vitiligo patients, both in skin and blood samples [25]. However, the study suggested there may be a possible defect in TGF‐β mediated suppression activity either due to defective TGF‐β signalling pathway or existence of TGF‐β inhibitory effector molecules.…”

Section: Discussionmentioning

confidence: 82%

“…However, the study suggested there may be a possible defect in TGF-β mediated suppression activity either due to defective TGF-β signalling pathway or existence of TGF-β inhibitory effector molecules. Hence, future detailed studies are required to assess the role of TGF-β signalling pathway and TGF-β inhibitory effector molecules in GV disease activity [25,26]. Additionally, this calcium treated Tregs with enhanced immunosuppressive function effectively suppressed the proliferation of CD8 + and CD4 + T-cells and resulted into decreased IFN-γ production by these cells (Figure 6).…”

Section: Discussionmentioning

confidence: 99%

Calcium controlled NFATc1 activation enhances suppressive capacity of regulatory T cells isolated from generalized vitiligo patients

Giri

Bharti²,

Begum

et al. 2022

Immunology

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NFATs and FOXP3 are linked with impaired regulatory T-cells (Tregs) in generalized vitiligo (GV). To elucidate calcium mediated NFATc1 signalling pathway and its effect on Treg suppressive capacity in GV. Calcium levels, calcineurin, NFATc1 and GSK-3β activity and cell proliferation were assessed in 52 GV patients and 50 controls by calcium assay kit, calcineurin phosphatase assay kit, TransAM NFATc1 kit, GSK-3β ELISA and BrdU cell proliferation assay. Transcripts (CNB, CAM, GSK3B, DYRK1A and calcium channel genes) and protein (IFN-γ, IL-10 and TGF-β) expressions were assessed by qPCR and ELISA, respectively. Reduced plasma and intracellular Tregs calcium levels and ORAI1 transcripts suggested altered calcium homeostasis in GV Tregs (p = 0.00387, p = 0.0048, p < 0.0001), which led to decreased calcineurin and NFATc1 activity in GV Tregs (p = 0.0299, p < 0.0001). CNB and CAM transcripts were reduced in GV Tregs (p < 0.0001, p = 0.0004). GSK-3β activity, GSK3B and DYRK1A transcripts significantly

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“…In contrast, Zhou et al (14) demonstrated an elevated level of TGF-β1 in patients with active non segmental vitiligo as compared to race-, gender-and age-matched healthy subjects. Moreover the level of serum TGF-β1 in 38 vitiligo patients showed no significant difference in comparison to control group as established by Ghanem et al (15) .So TGF-β1 might play a role in the pathogenesis of vitiligo related to the suppressive function of Tregs.…”

Section: Discussionmentioning

confidence: 77%

Estimate the Serum Level of IL-17A and TGF-?1 1 in Iraqi Generalized Vitiligo Patients

Shatha F. Tariq

2020

Indian Journal of Forensic Medicine & Toxicology

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Vitiligo is an acquired idiopathic skin disease characterized by white macules result from the destruction of melanocytes. Several cytokines have been implicated in the pathogenesis of vitiligo, keeping this in view the current study aimed to evaluate the serum levels of IL-17A and TGF-β1 in 25 patients with generalized vitiligo and compared them with healthy individuals in order to investigate whether these cytokines imbalances plays a role in the pathogenesis of this depigmentary disorder. Results of the present study showed that the serum level of IL-17A in vitiligo patients was increased significantly (p≤ 0.05) while the serum level of TGF-β1 was decreased significantly (p≤ 0.05) as compared with healthy control. According to the gender of patients, males had a slightly non-significant increased (p<0.05) in the level of IL-17A and TGF-β1 as compared with females. Patients with early onset vitiligo had non-significant increased (p<0.05) in the level of IL-17A and TGF-β1 as compared with late onset vitiligo patients. No significant differences (p<0.05) were detected in the levels of IL-17A and TGF-β1 in patients regarding the clinical types of vitiligo, family history and Koebner phenomenon. Patients with active disease had a significant increase (p≤0.05) in the level of IL-17A, though a significant decrease (p≤0.05) in the level of TGF-β1 was noticed as compared with both patients with stable disease and healthy control groups. Serum levels of both IL-17A and TGF-β1 have been shown to be negatively correlated with the disease duration (r=-0.174, p=0.405) and (r=-0.057, p=0.788) respectively.

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Transforming Growth Factor-β1 in the Skin and Serum of Patients with Non-segmental Vitiligo

Cited by 3 publications

References 24 publications

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

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

Calcium controlled NFATc1 activation enhances suppressive capacity of regulatory T cells isolated from generalized vitiligo patients

Estimate the Serum Level of IL-17A and TGF-?1 1 in Iraqi Generalized Vitiligo Patients

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