Tsukuba, Japan—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 this study, 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.
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This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology and Japan Society for the Promotion of Science (grant number 21H02959) and by JST, the establishment of university fellowships towards the creation of science technology innovation (grant number JPMJFS2106).
Title of original paper:
Mechanisms of age-related Treg dysfunction in an arthritic environment
Journal:
Clinical Immunology
DOI:
10.1016/j.clim.2024.110337
Professor MATSUMOTO, Isao
Institute of Medicine, University of Tsukuba
NISHIYAMA, Taihei
Doctoral Program in Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba
Clinical Immunology
Mechanisms of age-related Treg dysfunction in an arthritic environment
5-Aug-2024