Tu134 - Functional Alterations of Regulatory T Cells in Elderly-onset Arthritis

Abstract Text: [Objective] To clarify age-related alterations of regulatory T cells (Tregs) in rheumatoid arthritis (RA) patients and GPI-induced arthritis (GIA) mice.
[Method] 1) RNA-seq of Tregs from aged and young healthy subjects (HC) and untreated RA patients was performed.
2) GIA was induced in young and old mice after Treg depletion, and the arthritis scores were compared.
3) Tregs were isolated from young and aged GIA and naïve mice, and their inhibitory functions were evaluated by suppression assay and cell metabolism assay.
4) CD4+ T cells were isolated from inguinal lymph nodes of GIA and control young and aged mice, and single cell RNA-seq was performed to find specific DEGs in Treg clusters.
5) Functional changes in young and aged Tregs induced by interferon (IFN)-β were evaluated by suppression assay and qPCR.
[Results] 1) Aged Tregs were less activated than young ones in RA, and this difference was not detected in HC. In addition, pathway analysis of genes that varied between young and aged RA Tregs showed that IFN-related pathways were enriched.
2) The arthritis was significantly worsened only in the young mice.
3) Aged Tregs showed lower inhibitory function and OCR under GIA.
4) Treg clusters from aged mice showed enhanced type I IFN signaling.
5) Treatment with IFN-β resulted in decreased suppressive function of aged Tregs and increased expression of PD-1.
[Conclusion] It was suggested that in elderly-onset arthritis, type I IFN signaling in aged Tregs was enhanced and PD-1 expression was elevated, leading to the impaired Treg function.