by University of Tsukuba

Uncovering the cause of regulatory T-cell dysfunction in elderly onset rheumatoid arthritis

Graphical abstract. Credit: Clinical Immunology (2024). DOI: 10.1016/j.clim.2024.110337

Researchers at Tsukuba University have discovered that the increase in regulatory T (Treg) cells, which typically suppress immune responses, does not adequately control elderly-onset rheumatoid arthritis. In the arthritic environment, Treg cells exhibit altered metabolic activity, reduced suppressive function, and increased PD-1 expression. Moreover, increased type I interferon signaling has been identified as a contributing factor to this dysfunction.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation of multiple joints, with regulatory T (Treg) cell dysfunction playing a key role in its development. The incidence of elderly-onset RA (EORA) is rising, and these patients often face additional complications, including inflammation in other organs, infections, and cancer due to aggressive treatments. However, the age-related functional changes in patients with RA have not been fully elucidated.

In a study published in Clinical Immunology, researchers examined T cells in patients with RA and discovered that although the proportion of Treg cells is higher in patients with EORA than in those with young-onset RA, their activity is decreased.

RNA sequencing analysis revealed distinct Treg cell clusters between young and old patients with RA, a difference not observed in healthy subjects. Using mouse models of arthritis, the researchers observed decreased inhibitory function and oxygen consumption rates in Treg cells from mice with old-onset arthritis.

Moreover, type I interferon (IFN) signaling was enhanced in Treg cells from both EORA patients and aged arthritic mice, with IFN-β further reducing the inhibitory function of aged Treg cells.

These findings suggest that enhanced type I IFN signaling in aged Treg cells, induced specifically in the arthritic environment, is associated with impaired Treg cell function and contributes to the pathology of EORA.

More information: Taihei Nishiyama et al, Mechanisms of age-related Treg dysfunction in an arthritic environment, Clinical Immunology (2024). DOI: 10.1016/j.clim.2024.110337

Journal information: Clinical Immunology 

Provided by University of Tsukuba