Downregulation of type I interferon signalling pathway by urate in primary human PBMCs.

Autor: Badii M; Department of Medical Genetics, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.; Department of Internal Medicine and Research Institute for Medical Innovation, Radboud University Medical Centre, Nijmegen, The Netherlands., Nica V; Department of Medical Genetics, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania., Straton AR; Department of Medical Genetics, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania., Kischkel B; Department of Internal Medicine and Research Institute for Medical Innovation, Radboud University Medical Centre, Nijmegen, The Netherlands., Gaal O; Department of Medical Genetics, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.; Department of Internal Medicine and Research Institute for Medical Innovation, Radboud University Medical Centre, Nijmegen, The Netherlands., Cabău G; Department of Medical Genetics, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania., Klück V; Department of Internal Medicine and Research Institute for Medical Innovation, Radboud University Medical Centre, Nijmegen, The Netherlands., Hotea I; Department of Medical Genetics, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania., Novakovic B; Murdoch Children's Research Institute and Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Parkville, Victoria, Australia., Pamfil C; Department of Rheumatology, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania., Rednic S; Department of Rheumatology, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania., Netea MG; Department of Internal Medicine and Research Institute for Medical Innovation, Radboud University Medical Centre, Nijmegen, The Netherlands., Popp RA; Department of Medical Genetics, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania., Joosten LAB; Department of Medical Genetics, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.; Department of Internal Medicine and Research Institute for Medical Innovation, Radboud University Medical Centre, Nijmegen, The Netherlands., Crișan TO; Department of Medical Genetics, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.; Department of Internal Medicine and Research Institute for Medical Innovation, Radboud University Medical Centre, Nijmegen, The Netherlands.
Jazyk: angličtina
Zdroj: Immunology [Immunology] 2024 Oct 01. Date of Electronic Publication: 2024 Oct 01.
DOI: 10.1111/imm.13858
Abstrakt: Type I interferons (IFN1s) mediate innate responses to microbial stimuli and regulate interleukin (IL)-1 and IL-1 receptor antagonist (Ra) production in human cells. This study explores interferon-stimulated gene (ISG) alterations in the transcriptome of patients with gout and stimulated human primary cells in vitro in relation to serum urate concentrations. Peripheral blood mononuclear cells (PBMCs) and monocytes of patients with gout were primed in vitro with soluble urate, followed by lipopolysaccharide (LPS) stimulation. Separately, PBMCs were stimulated with various toll-like receptor (TLR) ligands. RNA sequencing and IL-1Ra cytokine measurement were performed. STAT1 phosphorylation was assessed in urate-treated monocytes. Cytokine responses to IFN-β were evaluated in PBMCs cultured with or without urate and restimulated with LPS and monosodium urate (MSU) crystals. Transcriptomics revealed suppressed IFN-related signalling pathways in urate-exposed PBMCs or monocytes which was supported by diminishment of phosphorylated STAT1. The stimulation of PBMCs with IFN-β did not modify the urate-induced inflammation. Interestingly, in vivo, serum urate concentrations were inversely correlated to in vitro ISG expression upon stimulations with TLR ligands. These findings support a deficient IFN1 signalling in the presence of elevated serum urate concentrations, which could translate to increased susceptibility to infections.
(© 2024 The Author(s). Immunology published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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