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Effect of narrow band-ultraviolet B on CD4(+) CD25(high) FoxP3(+) T-lymphocytes in the peripheral blood of vitiligo patients. Moftah Nayera H,El-Barbary Rasha A H,Ismail Mona A,Ali Nancy A M Photodermatology, photoimmunology & photomedicine BACKGROUND:It is widely believed that an imbalance between activated CD8(+) T cells and regulatory T cells (Tregs) exists in patients with vitiligo. Although there is evidence that narrow band ultraviolet (NB-UVB) irradiation can induce Tregs' number and activity, but up to our knowledge, none of the published studies involved the possible effect of NB-UVB on Tregs in vitiligo. OBJECTIVE:To evaluate the effect of NB-UVB on circulating CD4(+) CD25(high) FoxP3(+) regulatory T cells (FoxP3(+) Tregs) in vitiligo. METHODS:This prospective analytic study included 20 patients with active non-segmental vitiligo and 20 healthy controls. The patients were exposed to NB-UVB therapy three times per week for 30 sessions. Blood sampling before and after NB-UVB phototherapy was done to evaluate circulating CD4(+) CD25(high) Tregs and Foxp3(+) Tregs. RESULTS:The CD4(+) CD25(high) Tregs% and FoxP3(+) Tregs% were significantly higher in vitiligo patients compared with controls. NB-UVB therapy decreased both of them in patients, but they did not reach those of controls. Each of circulating CD4(+) CD25(high) Tregs% and FoxP3(+) Tregs% didn't correlate with either extent or activity of vitiligo before or after NB-UVB. CONCLUSION:Tregs functional defect is probably having an impact on NSV. NB-UVB may improve the function of Tregs. Understanding the mechanisms through which NB-UVB exert its effect on reducing the number of circulating Tregs would help open up the paths for future therapeutic options. 10.1111/phpp.12104
Circulating CD4(+) CD25(high) FoxP3(+) T-regulatory cells in patients with atopic dermatitis after narrowband-ultraviolet B phototherapy. El Samahy May H,Attia Enas A S,Saad Abeer A,Mahmoud Eman Y International journal of dermatology BACKGROUND:Previous studies showed controversial results regarding CD4(+) CD25(high) FoxP3(+) T-regulatory cells (Tregs) in atopic dermatitis (AD) and effect of therapy. METHODS:Circulating CD4(+) CD25(high) FoxP3(+) Tregs were assessed by flow cytometry in 20 controls and 20 patients with AD at baseline and after narrowband ultraviolet B with assessment of disease severity. RESULTS:Patients showed higher pretreatment T-effector cells (Teffs) (%) and lower pretreatment Tregs FoxP3 expression% than controls (P = 0.003 and 0.01, respectively). Mild AD showed a lower Tregs/Teffs ratio compared to controls (P = 0.013), while moderate group showed higher Teffs%, and lower Tregs FoxP3 expression% and Tregs/Teffs compared to controls (P = 0.016, 0.007, and 0.009 respectively). The severe group had higher Tregs% and Teffs%, yet with a lower Tregs FoxP3 expression% compared to controls (P < 0.001, P = 0.043, P = 0.044, respectively). There was significant reduction of severity after narrowband ultraviolet B (P = 0.007), with overall significant elevation of Tregs FoxP3 expression% in patients (P = 0.004). All patients' post-treatment laboratory findings were statistically matched to each other and to controls whatever their previous severity or therapeutic response. The improvement of severity score correlated with the change in both Tregs% and Tregs/Teffs. CONCLUSIONS:Significant reduction in AD disease severity is correlated with the change in Tregs% and Tregs/Teffs. 10.1111/ijd.12801
Epigenetic Variability of CD4+CD25+ Tregs Contributes to the Pathogenesis of Autoimmune Diseases. Shu Ye,Hu Qinghua,Long Hai,Chang Christopher,Lu Qianjin,Xiao Rong Clinical reviews in allergy & immunology Autoimmune diseases are characterized by aberrant immune responses against healthy cells and tissues. However, the exact mechanisms underlying the development of these conditions remain unknown. CD4+CD25+ regulatory T cells (Tregs) are a subset of mature T cells which have an important role in maintaining immune homeostasis and preventing autoimmune diseases. Forkhead box p3 (Foxp3), a member of the fork head transcription factor family, is recognized as a marker of CD4+CD25+ Tregs. The decreased number and/or function of CD4+CD25+ Tregs in peripheral blood and related tissues has been demonstrated in systemic lupus erythematosus, systemic sclerosis, and other autoimmune diseases, which are at least partially regulated by epigenetic mechanisms. Epigenetics refers to the study of potentially heritable alterations in gene expression without underlying changes of the nucleotide sequence, mainly including DNA methylation, histone modification, and microRNAs (miRNAs). For example, DNA methylation status of CpG islands on the Foxp3 gene, which may be affected by normal aging and regulated by environmental factors, plays an important role in modulating the homeostasis of Foxp3 expression in Tregs. Foxp3 gene in Tregs also shows distinct acetylation and trimethylation levels of histone H3 and H4 when compared with effector T cells, leading to an open chromatin structure. MicroRNAs such as miR-155, miR-126, and miR-10a also exert an important influence on the differentiation, development, and immunological functions of Tregs. Aberrant epigenetic modifications affecting Foxp3 and other key genes in Tregs contribute to disease activity and tissue inflammation in autoimmune diseases, which holds great potential for providing novel targets for epigenetic therapies. Advances in research into the epigenetic regulation of CD4+CD25+ Tregs may also lead to the identification of new epigenetic biomarkers for diagnosis and prognosis. 10.1007/s12016-016-8590-3