Immunosenescence of T cells: a key player in rheumatoid arthritis

Age‐related genes USP2 and ARG2 are involved in the reduction of immune cell infiltration in elderly patients with rheumatoid arthritis

“…Compared with age-matched healthy patients, RA patients show abnormally accelerated immunosenescence, especially T cell aging. 3,13 Congruously, we found that levels of Th1, Th2, Th17 and CD8 + T cells and TCR pathway were significantly reduced in established EPRA, but not in early EPRA. Abnormal TCR signaling and the loss of costimulatory molecule CD28 can affect the proliferation and activation of naive T cells and aggravate T cell aging and progression of disease.…”

“…23 Metabolic reprogramming of immune cells is associated with the senescent phenotype and tissue invasive ability. 13 Overall, with the progression of RA, the impact of age and immunosenescence gradually accumulated, inducing chronic synovial inflammation, tissue damage and the occurrence of complications. T cell senescence and related metabolic pathways may be a therapeutic target for improving RA.…”

“…Next, we used four online miRNA databases to search for miRNAs that might regulate these six hub genes and constructed a regulatory network including 25 miRNAs and six mRNAs (Figure 5C). USP2 was regulated by the most miRNAs (13), while miR-24-3p had the most target genes (three) and the other seven miRNAs had two target genes. Pathway enrichment analysis of the eight miRNAs indicated that they were mainly enriched in glycosphingolipid and glycosaminoglycan biosynthesis, fatty acid biosynthesis and metabolism, which was partly similar to the pathway enrichment of age-related DEGs (Figure 5D).…”

“…11 However, with the onset of immunosenescence in EPRA, T cell diversity, costimulatory control signals and the B cell response to primary antigen attack are lost, and dendritic cell function becomes abnormal. 12,13 Therefore, changes in immune cell infiltration in EPRA may be responsible for fewer rheumatoid factors and positivity for antibodies against cyclic citrullinated peptides (ACPA), poorer functional outcomes, different pro-inflammatory cytokine profiles and different treatment outcomes compared with those of YPRA. 8,14 Uncovering the mechanisms behind immunosenescence may help illuminate the pathogenesis of YPRA and inform treatment strategies for EPRA.…”

“…The synovial membrane is the main pathological tissue of RA, and the infiltration of mononuclear cells dominated by synovio‐tropic T cells and macrophages is the main characteristic of RA 11 . However, with the onset of immunosenescence in EPRA, T cell diversity, costimulatory control signals and the B cell response to primary antigen attack are lost, and dendritic cell function becomes abnormal 12,13 . Therefore, changes in immune cell infiltration in EPRA may be responsible for fewer rheumatoid factors and positivity for antibodies against cyclic citrullinated peptides (ACPA), poorer functional outcomes, different pro‐inflammatory cytokine profiles and different treatment outcomes compared with those of YPRA 8,14 .…”