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. 2021 Jun;37(6):520-527.
doi: 10.1002/kjm2.12356. Epub 2021 Jan 13.

Level of Foxp3, DNMTs, methylation of Foxp3 promoter region, and CD4 + CD25 + CD127low regulatory T cells in vulvar lichen sclerosus

Lin Wang, Jin-Ling Yi  1 , Hai-Yan Chen  1 , Pei-Liang Wang  1 , Yan-Li Shen  1
Affiliations

Level of Foxp3, DNMTs, methylation of Foxp3 promoter region, and CD4 + CD25 + CD127low regulatory T cells in vulvar lichen sclerosus

Lin Wang et al. Kaohsiung J Med Sci. 2021 Jun.

Abstract

This study is to investigate the pathogenesis of vulvar lichen sclerosus (VLS) by analyzing the level of Foxp3, DNMTs, methylation of Foxp3 promoter region, and CD4 + CD25 + CD127low Regulatory T cells (Tregs). This study enrolled 15 VLS patients and 25 controls. Lesional and extralesional vulvar skin tissues, normal vulvar skin tissues and peripheral blood were collected. Compared with the control group, Foxp3 protein in the lesional and extralesional skin of VLS group was significantly reduced. The levels of DNMT1 and DNMT3b proteins in lesional skin of VLS group were significantly increased. There was no difference in the total methylation rates of the promoter region of the Foxp3 gene. The methylation rates of CpG1, CpG4, CpG9, and CpG10 were significantly higher in lesional skin of VLS group than in control group. There was no correlation between the total methylation rates of 10 CpG sites and the level of Foxp3 and DNMT1 proteins; there was a positive correlation between Foxp3 and DNMT1 protein in lesional skin of VLS group (r = 0.675, p < 0.05), and a negative correlation (r = -0.665, p < 0.05) in extralesional skin of VLS group. However, there was no correlation of Foxp3 with DNMT3b. The number of CD4 + CD25 + CD127low Tregs VLS decreased significantly. The expression of Foxp3 protein and the quantity of CD4 + CD25 + CD127low Tregs in patients with VLS decreased, which may cause local or systemic abnormal immunosuppression of Tregs, leading to the occurrence of VLS. This may be related with methylation or DNMT1, which needs further verification.

Keywords: CD127; CD4 + CD25+ Treg; Foxp3; methylation; vulvar lichen sclerosus.

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Conflict of interest statement

All authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Analysis of methylation rates. (A) Total methylation rates in the promoter region of Foxp3 gene in the lesional skin and extralesional skin of VLS group, and the control group. (B) Methylation rates of 10 CpG sites in the promoter region of Foxp3 gene.*comparing with the control group, p < 0.05; # comparing with the extralesional skin of VLS group, p < 0.05. VLS, vulvar lichen sclerosus
FIGURE 2
FIGURE 2
Expression of Foxp3, DNMT1, and DNMT3b proteins. Western blot was performed to detect protein expressions in the lesional skin and extralesional skin of VLS group, and the control group. (A) Representative Western blot results. (B) Relative level of Foxp3 protein. (C) Relative level of of DNMT1 protein. (D) Relative level of DNMT3b. *p < 0.05. VLS, vulvar lichen sclerosus
FIGURE 3
FIGURE 3
Comparison of the quantity of CD4 + CD25 + CD127Low Tregs in peripheral blood between the VLS group and the control group. Flow cytometry was used to detect CD4 + CD25 + CD127Low Tregs in peripheral blood. (A) Representative flow cytometry results. The gating strategy was shown. (B) Quantitative flow cytometry results of CD4 + CD25 + CD127Low Tregs. *p < 0.05. VLS, vulvar lichen sclerosus
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