Negative impact of Interleukin-9 on synovial regulatory T cells in rheumatoid arthritis

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2023-12, Vol.257, p.109814-109814, Article 109814
• Main Authors: Chakraborty, Sushmita, Gupta, Ranjan, Kubatzky, Katharina F., Kar, Santanu, Kraus, Franziska V., Souto-Carneiro, M. Margarida, Lorenz, Hanns-Martin, Kumar, Pankaj, Kumar, Vijay, Mitra, Dipendra Kumar
• Format: Article
• Language: English
• Subjects: Arthritis, Rheumatoid - metabolism; Cytokines; Humans; Inflammation; Inflammatory cytokines; Interleukin −9; Interleukin-9 - metabolism; Regulatory T cells; Rheumatoid arthritis; Synovial Fluid; Synovial Membrane; T-Lymphocytes, Regulatory - metabolism
• ISSN: 1521-6616; 1521-7035; 1521-7035
• DOI: 10.1016/j.clim.2023.109814

In Rheumatoid Arthritis (RA), regulatory T cells (Tregs) have been found to be enriched in the synovial fluid. Despite their accumulation, they are unable to suppress synovial inflammation. Recently, we showed the synovial enrichment of interleukin-9 (IL-9) producing helper T cells and its positive correlation with disease activity. Therefore, we investigated the impact of IL-9 on synovial Tregs in RA. Here, we confirmed high synovial Tregs in RA patients, however these cells were functionally impaired in terms of suppressive cytokine production (IL-10 and TGF-β). Abrogating IL-9/ IL-9 receptor interaction could restore the suppressive cytokine production of synovial Tregs and reduce the synovial inflammatory T cells producing IFN-γ, TNF-α, IL-17. However, blocking these inflammatory cytokines failed to show any effect on IL-9 producing T cells, highlighting IL-9's hierarchy in the inflammatory network. Thus, we propose that blocking IL-9 might dampen synovial inflammation by restoring Tregs function and inhibiting inflammatory T cells. •Interleukin 9 (IL-9) negatively influences the immunosuppressive cytokine production by regulatory T cell.•Blocking IL-9 interaction with its receptor could restore immunosuppressive cytokine production by synovial fluid-derived regulatory T cells and inhibit synovial inflammatory T cells.•Blocking the IL-9 may constitute a novel therapeutic approach for inhibiting synovial inflammation in RA.