Expression of Th17‐ and Treg‐specific transcription factors in vitiligo patients

Abstract

Background Vitiligo is mainly considered an autoimmune skin disease as the number of IL‐17 producing Th17 cells, involved in the development of autoimmune and inflammatory pathologies, increased in vitiligo skin. T regulatory cells (Tregs) seem to be altered during the disease. Thus, there must be some upstream molecular factors that regulate the cellular response to apoptotic and inflammatory stimuli. Objectives To investigate the expression of Th17‐ and Treg‐specific transcription factors in PBMCs and to evaluate the correlation between these transcription factors and cytokines in vitiligo patients. Methods We investigated 30 active NSV patients for Th17‐ and Treg‐specific transcription factors RORγt (retinoic acid‐related orphan receptor gamma t), FOXP3 (forkhead/winged helix), HELIOS, EOS, and IRF4 (Interferon Regulatory Factor 4) as well as apoptotic marker NALP1 (NACHT‐leucine‐rich‐repeat protein 1) in PBMCs with RT‐qPCR. Immunostaining was done for transcription factors and cytokines on skin sections. Results The mRNA level of FOXP3 was significantly lower in patients (0.76 fold, P < 0.001), whereas RORγt was slight but not significantly increased (0.76 fold, P = 0.06). Furthermore, NALP1 in lymphocytes was found to be increased in patients (0.69 fold, P < 0.01). The immunostaining results revealed increased expression of RORγ, IL‐17A, NALP1, and IL‐1β in vitiligo skin when compared to normal healthy skin. Conclusion Reduced FOXP3/RORγt mRNA ratio suggests thriving of the Th17 cell population in PBMCs of vitiligo patients. Increased NALP1 levels indicate the existence of an apoptotic phenomenon which correlates with the increased expression of IL‐1β in vitiligo pathogenesis.

Effect of Narrow Band –UVB Phototherapy on Circulating T-Regulatory cells and Serum IL-17 Level in Egyptian Patients with Non-Segmental Vitiligo

“…In our study, the mean age of vitiligo onset was 26.5 ± 8.3 years. This is in accordance with the finding of Bhardwaj et al (15) who reported that the mean age at onset of vitiligo was 20.8 ± 10.0 years. On the contrary, Martins et al (16) have found that the average age of onset of nonsegmental vitiligo was 6.1 ± 3.1years.…”

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

“…Additionally, our meta-analysis suggested the role of decreased FOXP3 expression in disease activity of vitiligo (Figure S1a ). These results were in concordance with the previous studies [ 5 , 9 , 17 – 20 , 22 , 24 – 26 ]. The decreased FOXP3 protein and transcript levels in the blood may be due to the reduced Tregs' frequency in vitiligo patients; therefore, our meta-analysis further suggests for the role of decreased Tregs' frequency in vitiligo pathogenesis.…”

“…Forkhead box P3 (FOXP3) is a key transcription factor of Tregs; it regulates the production of Tregs' suppressive molecules such as TGF- β , CTLA-4, IL-10, and GITR [ 23 ]. However, FOXP3 expression has been found to be altered in vitiligo patients [ 5 , 9 , 17 – 20 , 22 , 24 – 26 ]. Additionally, IL-10 and TGF- β , the key immunosuppressive cytokines produced by Tregs, govern the development of iTreg cells and participate in peripheral tolerance preservation and peripheral Treg cell maintenance [ 27 ].…”

Antigen Specificity Enhances Disease Control by Tregs in Vitiligo

“…In turn, these innate immune cells and APCs recruit auto-reactive T cells to mediate specific destruction of melanocytes in vitiligo (10). The loss of tolerance to self-antigens also involves reduced cutaneous regulatory T cell (Treg) activity (11,12). Tregs are subsets of T cells responsible for peripheral tolerance via suppression of immune cells, including self-reactive, cytotoxic T cells, to maintain immune homeostasis (13).…”