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.

Th17 cell pathogenicity and plasticity in rheumatoid arthritis

“…Accordingly, Th17 cells, which not only elicited synovial inflammation and pannus formation, but also promoted articular cartilage and bone destruction, have been implicated in RA. In addition, distinct effector subsets of CD4 + Th cells were also involved in the pathology of RA . Hence, further studies on the interaction between Th17 and other Th cells contributed to revealing the immunologic mechanism of RA.…”

Clinical Impact of Interferon-γ in Anti-Citrullinated Protein Antibody-Positive Rheumatoid Arthritis

“…Helper T cells (cluster of differentiation [CD] 4 + T cells) are important elements in adaptive immune systems and can be divided into several subtypes [6]. In in amed RA synovium, CD4 + T cells are predominant [7], suggesting that CD4 + T cells may be cornerstone immune cells in RA pathogenesis.…”

“…Type 17 helper T cells (Th17 cells) have been identi ed in RA [8,9], and before identifying Th17 cells, interferon (IFN)-γ-secreting Th1 cells have been thought as major pathologic cells in RA development [10]. IFN-γ is the main cytokine produced by Th1 cells [6], and autoreactive Th1 cells are increased in the peripheral blood and synovial uid of patients with RA [11,12]. However, the effects of IFN-γ in animal models are unclear [13][14][15].…”

Interpretable factor models of single-cell RNA-seq via variational autoencoders

“…The study of the regulatory architecture of cells has revealed numerous examples of co-regulation of transcription of large numbers of genes (Jang et al, 2017;Kondo et al, 2018), and this has been used to link the organization of cells to their distinct functions in response to developmental or external stimuli (Romero et al, 2012). While studies of cells in bulk have led to interesting population-level insights about the relationships between genes (Thompson et al, 2015), the study of individual cells via single-cell RNA-seq has led to questions about how the relationships between genes depend on cell type (Lindgren et al, 2017).…”