Aberrant histone modification and inflammatory cytokine production of peripheral CD4+ T cells in patients with oral lichen planus.

Jun Shen,Cao Yin,Xiao Jiang,Xuan Wang,Shujuan Yang,Guangbao Song

doi:10.1111/jop.12790

Jun Shen, Cao Yin + Show 4 more

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https://doi.org/10.1111/jop.12790

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Abstract

BackgroundsTo investigate alterations in histone modification and histone deacetylases (HDACs) in patients with oral lichen planus (OLP), and to evaluate correlations with inflammatory cytokine production.MethodsGlobal histone H3/H4 acetylation and HDAC activity in CD4+ T cells from 23 patients with OLP and 10 healthy control subjects were examined using spectrophotometry. The mRNA levels of eight members of four classes of HDAC genes were measured by real‐time quantitative polymerase chain reaction. Forty cytokines involved in inflammation were examined with a cytokine array. The correlation between histone modification and cytokine production was analyzed.ResultsGlobal histone H3 hypo‐acetylation was observed in OLP patients. Patients with OLP had significantly higher HDACs activity,and higher HDAC6 and HDAC7 mRNA level compared with the controls. Of the 40 cytokines in the cytokine array, eight were significantly increased in OLP patients: interleukin (IL)‐4, IL‐8, IL‐1ra, tumor necrosis factor receptor II (TNFR II), macrophage inflammatory protein 1b (MIP‐1b), fibrosis‐associated tissue inhibitors of metalloproteinase 1 (TIMP)‐1, monocyte chemotactic protein 1 (MCP‐1), and eotaxin‐2. In the OLP group, the acetylation level of histone H3 was negatively correlated with IL‐4 and MCP‐1 production, and the expression of HDAC6 mRNA was positively correlated with MCP‐1 production. In the non‐erosive subgroup, acetylation of histone H3 was negatively correlated with IL‐4, IL‐16, and TIMP‐2 production. In the erosive OLP subgroup, the expression of HDAC7 mRNA was positively correlated with MIP‐1a production.ConclusionAberrant histone modification of CD4+ T cells in peripheral blood could occur in OLP patients, and possibly affects inflammatory cytokine production.

Highlights

| 141 been reported that histone modification is associated with several critical events in T cells, such as T cell development, activation, differentiation, and cytokine production.[18,19]
In patients with oral lichen planus (OLP), large numbers of T lymphocytes accumulate beneath the epithelium of the oral mucosa, contributing to the differentiation of the stratified epithelium, hyperkeratosis, and erythematous lesions
We showed for the first time that a histone of CD4+ T cells in peripheral blood was aberrantly modified and that the modification may be associated with the pathogenesis of OLP

Summary

| MATERIALS AND METHODS

Isolation of histones was performed using a Total Histone Extraction Kit (Epigentek, Brooklyn, New York City, NY). Global histone H3/H4 acetylation detection was performed using EpiQuikTM global histone H3/H4 acetylation assay kits according to the manufacturer's instructions (Epigentek). Isolation of nucleoprotein was performed using the EpiQuik Nuclear Extraction Kit (Epigentek). Nucleoprotein concentration was measured with the BCATM Protein Assay Kit (Pierce). Total RNA was isolated from CD4+ T cells using the RNeasy Mini kit (Tiangen Biotech Co., Ltd., Beijing, China) according to the manufacturer's instructions. Peripheral blood samples were collected from EOLP patients (n = 6) and NEOLP patients (n = 5), and age and sex matched to healthy controls (n = 5). The human cytokine antibody array (RayBiotech, Norcross, GA) capable of measuring 40 cytokines was used according to the manufacturer's instructions. The statistical significance was set at P ≤ 0.05

| RESULTS

Findings

| DISCUSSION