The role of interleukin-18 and interleukin-18 binding protein in K/BxN serum transfer-induced arthritis.

K/BxN serum transfer-induced arthritis Still’s disease interleukin-18 interleukin-18 binding protein rheumatoid arthritis systemic juvenile idiopathic arthritis

Journal

Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960

Informations de publication

Date de publication:
2023
Historique:
received: 01 05 2023
accepted: 24 05 2023
medline: 10 7 2023
pubmed: 7 7 2023
entrez: 7 7 2023
Statut: epublish

Résumé

Interleukin-18 is a proinflammatory cytokine, the activity of which is regulated by its natural inhibitor, IL-18 binding protein (IL-18BP). Elevated circulating levels of IL-18 have been observed in patients with systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD), two conditions associated with dysregulated innate immune responses. This study examines the expression and function of IL-18 and IL-18BP in K/BxN serum transfer arthritis (STA), a model that is uniquely dependent on innate immune responses. Naïve and serum transfer-induced arthritis (STA) wild-type (WT) mice were used to examine the articular levels of IL-18 and IL-18BP mRNA by RT-qPCR. The cellular sources of IL-18BP in the joints were determined by using IL-18 and IL-18BP mRNA levels were significantly increased in arthritic as compared to normal joints. Synovial neutrophils, macrophages, and endothelial cells represented the cellular sources of IL-18BP in arthritic joints, whereas IL-18BP production was limited to endothelial cells in non-inflamed joints. The incidence and severity of arthritis were similar in IL-18BP KO and IL-18 KO compared to their WT littermates. Transcript levels of different inflammatory cytokines were not different in the two KO mouse lines compared to WT mice. Although IL-18 and IL-18BP levels were increased in arthritic joints, our results show that the IL-18/IL-18BP balance is not involved in the regulation of STA.

Sections du résumé

Background
Interleukin-18 is a proinflammatory cytokine, the activity of which is regulated by its natural inhibitor, IL-18 binding protein (IL-18BP). Elevated circulating levels of IL-18 have been observed in patients with systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD), two conditions associated with dysregulated innate immune responses. This study examines the expression and function of IL-18 and IL-18BP in K/BxN serum transfer arthritis (STA), a model that is uniquely dependent on innate immune responses.
Methods
Naïve and serum transfer-induced arthritis (STA) wild-type (WT) mice were used to examine the articular levels of IL-18 and IL-18BP mRNA by RT-qPCR. The cellular sources of IL-18BP in the joints were determined by using
Results
IL-18 and IL-18BP mRNA levels were significantly increased in arthritic as compared to normal joints. Synovial neutrophils, macrophages, and endothelial cells represented the cellular sources of IL-18BP in arthritic joints, whereas IL-18BP production was limited to endothelial cells in non-inflamed joints. The incidence and severity of arthritis were similar in IL-18BP KO and IL-18 KO compared to their WT littermates. Transcript levels of different inflammatory cytokines were not different in the two KO mouse lines compared to WT mice.
Conclusion
Although IL-18 and IL-18BP levels were increased in arthritic joints, our results show that the IL-18/IL-18BP balance is not involved in the regulation of STA.

Identifiants

pubmed: 37415987
doi: 10.3389/fimmu.2023.1215364
pmc: PMC10320286
doi:

Substances chimiques

Interleukin-18 0
interleukin-18 binding protein 0
Cytokines 0
RNA, Messenger 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1215364

Informations de copyright

Copyright © 2023 Fauteux-Daniel, Merlo Pich, Girard-Guyonvarc’h, Caruso, Rodriguez and Gabay.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Sebastien Fauteux-Daniel (S)

Division of Rheumatology, Department of Medicine, Geneva University Hospitals, Geneva, Switzerland.
Department of Pathology and Immunology, University of Geneva, Faculty of Medicine, Geneva, Switzerland.
Geneva Centre for Inflammation Research, Geneva, Switzerland.

Laura M Merlo Pich (LM)

Division of Rheumatology, Department of Medicine, Geneva University Hospitals, Geneva, Switzerland.
Department of Pathology and Immunology, University of Geneva, Faculty of Medicine, Geneva, Switzerland.
Geneva Centre for Inflammation Research, Geneva, Switzerland.

Charlotte Girard-Guyonvarc'h (C)

Division of Rheumatology, Department of Medicine, Geneva University Hospitals, Geneva, Switzerland.
Department of Pathology and Immunology, University of Geneva, Faculty of Medicine, Geneva, Switzerland.
Geneva Centre for Inflammation Research, Geneva, Switzerland.

Assunta Caruso (A)

Division of Rheumatology, Department of Medicine, Geneva University Hospitals, Geneva, Switzerland.
Department of Pathology and Immunology, University of Geneva, Faculty of Medicine, Geneva, Switzerland.
Geneva Centre for Inflammation Research, Geneva, Switzerland.

Emiliana Rodriguez (E)

Division of Rheumatology, Department of Medicine, Geneva University Hospitals, Geneva, Switzerland.
Department of Pathology and Immunology, University of Geneva, Faculty of Medicine, Geneva, Switzerland.
Geneva Centre for Inflammation Research, Geneva, Switzerland.

Cem Gabay (C)

Division of Rheumatology, Department of Medicine, Geneva University Hospitals, Geneva, Switzerland.
Department of Pathology and Immunology, University of Geneva, Faculty of Medicine, Geneva, Switzerland.
Geneva Centre for Inflammation Research, Geneva, Switzerland.

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Classifications MeSH