Review: Transcriptional Regulation of CD4+ T Cell Differentiation in Experimentally Induced Arthritis and Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic inflammation of the joint synovium and infiltration by activated inflammatory cells. CD4+ T cells form a large proportion of the inflammatory cells invading the synovial tissue, and are involved in the RA pathologic process. In general, CD4+ T cells differentiate into various T helper cell subsets and acquire the functional properties to respond to specific pathogens, and also mediate some autoimmune disorders such as RA. Because the differentiation of T helper cell subsets is determined by the expression of specific transcription factors in response to the cytokine environment, these transcription factors are considered to have a role in the pathology of RA. Treg cells control an excess of T cell-mediated immune response, and the transcription factor FoxP3 is critical for the differentiation and function of Treg cells. Treg cell dysfunction can result in the development of systemic autoimmunity. In this review, we summarize how the expression of transcription factors modulates T helper cell immune responses and the development of autoimmune diseases, especially in RA. Understanding the role of transcription factors in the pathogenesis of autoimmunity may lead to novel therapeutic strategies to control the differentiation and function of both T helper cells and Treg cells.

Figure 1

Regulation of transcription factors involved in the pathogenesis of experimentally induced autoimmune arthritis. The potential relationships among various transcription factors involved in the pathology of rheumatoid arthritis (left) and experimentally induced autoimmune arthritis (right) are shown. APC = antigen‐presenting cell; IL‐6R = interleukin‐6 receptor; RORγt = retinoic acid receptor–related orphan nuclear receptor γt; IFNγR = interferon‐γ receptor; SOCS3 = suppressor of cytokine signaling 3; Ahr = aryl hydrocarbon receptor.