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

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...

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Main Authors: Chakraborty, Sushmita (Author) , Gupta, Ranjan (Author) , Hieke-Kubatzky, Katharina (Author) , Kar, Santanu (Author) , Kraus, Franziska V. (Author) , Souto-Carneiro, Maria Margarida (Author) , Lorenz, Hanns-Martin (Author) , Kumar, Pankaj (Author) , Kumar, Vijay (Author) , Mitra, Dipendra Kumar (Author)
Format: Article (Journal)
Language:English
Published: December 2023
In: Clinical immunology
Year: 2023, Volume: 257, Pages: 1-13
ISSN:1521-7035
DOI:10.1016/j.clim.2023.109814
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.clim.2023.109814
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1521661623005776
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Author Notes:Sushmita Chakraborty, Ranjan Gupta, Katharina F. Kubatzky, Santanu Kar, Franziska V. Kraus, M. Margarida Souto-Carneiro, Hanns-Martin Lorenz, Pankaj Kumar, Vijay Kumar, Dipendra Kumar Mitra
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Summary: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.
Item Description:Online verfügbar 23 October 2023, Version des Artikels 29 October 2023
Gesehen am 15.01.2024
Physical Description:Online Resource
ISSN:1521-7035
DOI:10.1016/j.clim.2023.109814

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