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

Autor: Chakraborty S; Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, New Delhi 110029, India; Department of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg University, Im Neuenheimer Feld 324, Heidelberg 69120, Germany., Gupta R; Department of Rheumatology, All India Institute of Medical Sciences, New Delhi 110029, India., Kubatzky KF; Department of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg University, Im Neuenheimer Feld 324, Heidelberg 69120, Germany., Kar S; Department of Orthopaedics, All India Institute of Medical Sciences, New Delhi 110029, India., Kraus FV; Division of Rheumatology, Department of Internal Medicine 5 Hematology-Oncology-Rheumatology, Heidelberg University Hospital, Im Neuenheimer Feld 410, Heidelberg 69120, Germany., Souto-Carneiro MM; Division of Rheumatology, Department of Internal Medicine 5 Hematology-Oncology-Rheumatology, Heidelberg University Hospital, Im Neuenheimer Feld 410, Heidelberg 69120, Germany., Lorenz HM; Division of Rheumatology, Department of Internal Medicine 5 Hematology-Oncology-Rheumatology, Heidelberg University Hospital, Im Neuenheimer Feld 410, Heidelberg 69120, Germany., Kumar P; Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, New Delhi 110029, India., Kumar V; Department of Orthopaedics, All India Institute of Medical Sciences, New Delhi 110029, India., Mitra DK; Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, New Delhi 110029, India. Electronic address: salilmitra2@gmail.com.
Jazyk: angličtina
Zdroj: Clinical immunology (Orlando, Fla.) [Clin Immunol] 2023 Dec; Vol. 257, pp. 109814. Date of Electronic Publication: 2023 Oct 23.
DOI: 10.1016/j.clim.2023.109814
Abstrakt: 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.
Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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