The Search for the Pathogenic T Cells in the Joint of Rheumatoid Arthritis: Which T-Cell Subset Drives Autoimmune Inflammation?

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disorder affecting systemic synovial tissues, leading to the destruction of multiple joints. Its etiology is still unknown, but T-cell-mediated autoimmunity has been thought to play critical roles, which is supported by experimental as well as clinical observations. Therefore, efforts have been made to elucidate the functions and antigen specificity of pathogenic autoreactive T cells, which could be a therapeutic target for disease treatment. Historically, T-helper (Th)1 and Th17 cells are hypothesized to be pathogenic T cells in RA joints; however, lines of evidence do not fully support this hypothesis, showing polyfunctionality of the T cells. Recent progress in single-cell analysis technology has led to the discovery of a novel helper T-cell subset, peripheral helper T cells, and attracted attention to the previously unappreciated T-cell subsets, such as cytotoxic CD4 and CD8 T cells, in RA joints. It also enables a comprehensive view of T-cell clonality and function. Furthermore, the antigen specificity of the expanded T-cell clones can be determined. Despite such progress, which T-cell subset drives inflammation is yet known.

Molecular mechanism of Xiaohuoluo wan for rheumatoid arthritis by integrating in vitro and in vivo chemomics and network pharmacology

“…T‐lymphocytes are an important compound of the immune system, and their activation can resist the attack of tumor cells and pathogenic organisms but also cause autoimmune diseases due to overactivation. TH17 cells generated from T‐lymphocyte differentiation discriminate corresponding cell subpopulations and secrete various inflammatory factors under various environmental stimuli, which in turn affect osteoclast activity and lead to RA (Yamada, 2023). For example, IL‐17 can be produced by Th17 cells, and IL‐17 can directly inhibit matrix synthesis by chondrocytes and produce enzymes that degrade cartilage matrix (Geboes et al, 2009; van den Berg & Miossec, 2009), triggering cartilage and bone inflammation and bone destruction.…”

Chikungunya-virus-specific CD4+T cells are associated with chronic chikungunya viral arthritic disease in humans

“…Another prevalent hypothesis in the field to explain CD4 + T cell pathogenicity is the idea of T cell- mediated autoimmunity, which is also a mechanism associated with rheumatoid arthritis (RA) 46–49 . Our findings are more in accordance with the latter hypothesis as we observed an enrichment of CCR6 + CXCR3 - , which are associated with Th17 cells, in the symptomatic group, while the recovered group exhibited a significantly higher CCR6 - CXCR3 + , which are associated with Th1 phenotype 34 .…”

Crosstalk between Inflammation and Atherosclerosis in Rheumatoid Arthritis and Systemic Lupus Erythematosus: Is There a Common Basis?

“…In RA joints, Tph cells and PD-1high CD4 T cells exhibit antibody-stimulating and proinflammatory functions. They can produce TNF-α, IFN-γ and GM-CSF, as well as IL-21 and CXCL13 [104].…”