DNA Methylation of T Lymphocytes as a Therapeutic Target: Implications for Rheumatoid Arthritis Etiology.

Jianan Zhao,Ping Jiang,Kai Wei,Dongyi He,Shicheng Guo,Lingxia Xu,Steven J Schrodi,Cen Chang

doi:10.3389/fimmu.2022.863703

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease that can cause joint damage and disability. Epigenetic variation, especially DNA methylation, has been shown to be involved in almost all the stages of the pathology of RA, from autoantibody production to various self-effector T cells and the defects of protective T cells that can lead to chronic inflammation and erosion of bones and joints. Given the critical role of T cells in the pathology of RA, the regulatory functions of DNA methylation in T cell biology remain unclear. In this review, we elaborate on the relationship between RA pathogenesis and DNA methylation in the context of different T cell populations. We summarize the relevant methylation events in T cell development, differentiation, and T cell-related genes in disease prediction and drug efficacy. Understanding the epigenetic regulation of T cells has the potential to profoundly translate preclinical results into clinical practice and provide a framework for the development of novel, individualized RA therapeutics.

Highlights

Rheumatoid arthritis (RA) is a chronic and systemic inflammatory illness that causes persistent synovial inflammation and bone and joint damage
There are several unresolved issues regarding the role of DNA methylation in RA
There may be several mechanisms by which DNA methylation yields effects, and these effects may be substantially different across cell types

Summary

INTRODUCTION

Rheumatoid arthritis (RA) is a chronic and systemic inflammatory illness that causes persistent synovial inflammation and bone and joint damage. The biological roles of the majority of the differential genes were shown to be associated with T cell development and activation by assessing gene expression and DNA methylation of CD4+ T cells in RA patients and healthy individuals [11]. Pathway analysis revealed that two of the top five were linked to T cells and cytokines [12] This suggests that the differential expression of RA genes may be partly driven by DNA methylation and are linked to variants of disease susceptibility genes that contribute to disease progression [11]. RA patient CD4+ T cells exhibit hypermethylated genes, including JUN, STAT1, PTEN, and CD44, compared to healthy controls, whereas hypomethylated genes include KRAS and ALB.

Potential association with RA

THE DEFECTS OF DNA METHYLATION IN TREG CELLS PROMOTE INFLAMMATION

CONCLUSION

Findings

AUTHOR CONTRIBUTIONS