Is T-cell senescence associated with inflammatory arthritis and disease burden? A systematic review

Abstract

Musculoskeletal and rheumatic diseases, such as rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), and psoriatic arthritis (PsA), are prevalent and are increasingly common worldwide. The aetiology of these diseases varies; some are linked to mechanical stress (e.g., osteoarthritis), while others, like RA and axSpA, are associated with autoimmune processes. Despite their different origins, these conditions share a common feature in elevated inflammatory profiles compared to healthy populations. In autoimmune diseases, immune cells-particularly T-cells-are chronically activated, and the regulatory system is unable to control this. Chronic activation and proliferation often lead to a state known as cellular senescence. Senescent T-cells develop distinct characteristics, including resistance to apoptosis and the adoption of a pro-inflammatory senescence-associated secretory phenotype (SASP). This phenotype contributes to disease progression by driving the release of pro-inflammatory cytokines and elevating circulating levels of inflammatory markers. This systematic review summarises the results from 20 studies, out of 3203 that were initially picked up by the search phrase, to investigate whether levels of senescent T-cells are correlated with disease burden in the three mentioned conditions (RA, axSpA, and PsA). Our findings indicate that the level of senescent T-cells (T-helper CD4 cells and cytotoxic CD8 T-cells) is higher in patients when compared to healthy populations, and with their altered characteristics, these senescent cells could mechanistically contribute to disease progression, hence symptom burden. However, further investigation is needed in this field to show whether this increased level is associated with disease burden or not.

Keywords: Axial spondyloarthritis; CD28; CD4; CD8; Psoriatic arthritis; Rheumatoid arthritis; T-lymphocytes.