The role of interleukin-18 and interleukin-18 binding protein in K/BxN serum transfer-induced arthritis
BackgroundInterleukin-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...
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1215364/full |
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| author | Sebastien Fauteux-Daniel Sebastien Fauteux-Daniel Sebastien Fauteux-Daniel Laura M. Merlo Pich Laura M. Merlo Pich Laura M. Merlo Pich Charlotte Girard-Guyonvarc’h Charlotte Girard-Guyonvarc’h Charlotte Girard-Guyonvarc’h Assunta Caruso Assunta Caruso Assunta Caruso Emiliana Rodriguez Emiliana Rodriguez Emiliana Rodriguez Cem Gabay Cem Gabay Cem Gabay |
| author_facet | Sebastien Fauteux-Daniel Sebastien Fauteux-Daniel Sebastien Fauteux-Daniel Laura M. Merlo Pich Laura M. Merlo Pich Laura M. Merlo Pich Charlotte Girard-Guyonvarc’h Charlotte Girard-Guyonvarc’h Charlotte Girard-Guyonvarc’h Assunta Caruso Assunta Caruso Assunta Caruso Emiliana Rodriguez Emiliana Rodriguez Emiliana Rodriguez Cem Gabay Cem Gabay Cem Gabay |
| author_sort | Sebastien Fauteux-Daniel |
| collection | DOAJ |
| description | BackgroundInterleukin-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.MethodsNaïve 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 Il18bp-tdTomato reporter knock-in mice. The incidence and severity of arthritis, including mRNA levels of different cytokines, were compared in IL-18BP or IL-18 knock-out (KO) mice and their WT littermates.ResultsIL-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.ConclusionAlthough 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. |
| first_indexed | 2024-03-13T04:05:09Z |
| format | Article |
| id | doaj.art-4a6d6914ddc34728996710f63811959e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-13T04:05:09Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-4a6d6914ddc34728996710f63811959e2023-06-21T08:00:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-06-011410.3389/fimmu.2023.12153641215364The role of interleukin-18 and interleukin-18 binding protein in K/BxN serum transfer-induced arthritisSebastien Fauteux-Daniel0Sebastien Fauteux-Daniel1Sebastien Fauteux-Daniel2Laura M. Merlo Pich3Laura M. Merlo Pich4Laura M. Merlo Pich5Charlotte Girard-Guyonvarc’h6Charlotte Girard-Guyonvarc’h7Charlotte Girard-Guyonvarc’h8Assunta Caruso9Assunta Caruso10Assunta Caruso11Emiliana Rodriguez12Emiliana Rodriguez13Emiliana Rodriguez14Cem Gabay15Cem Gabay16Cem Gabay17Division of Rheumatology, Department of Medicine, Geneva University Hospitals, Geneva, SwitzerlandDepartment of Pathology and Immunology, University of Geneva, Faculty of Medicine, Geneva, SwitzerlandGeneva Centre for Inflammation Research, Geneva, SwitzerlandDivision of Rheumatology, Department of Medicine, Geneva University Hospitals, Geneva, SwitzerlandDepartment of Pathology and Immunology, University of Geneva, Faculty of Medicine, Geneva, SwitzerlandGeneva Centre for Inflammation Research, Geneva, SwitzerlandDivision of Rheumatology, Department of Medicine, Geneva University Hospitals, Geneva, SwitzerlandDepartment of Pathology and Immunology, University of Geneva, Faculty of Medicine, Geneva, SwitzerlandGeneva Centre for Inflammation Research, Geneva, SwitzerlandDivision of Rheumatology, Department of Medicine, Geneva University Hospitals, Geneva, SwitzerlandDepartment of Pathology and Immunology, University of Geneva, Faculty of Medicine, Geneva, SwitzerlandGeneva Centre for Inflammation Research, Geneva, SwitzerlandDivision of Rheumatology, Department of Medicine, Geneva University Hospitals, Geneva, SwitzerlandDepartment of Pathology and Immunology, University of Geneva, Faculty of Medicine, Geneva, SwitzerlandGeneva Centre for Inflammation Research, Geneva, SwitzerlandDivision of Rheumatology, Department of Medicine, Geneva University Hospitals, Geneva, SwitzerlandDepartment of Pathology and Immunology, University of Geneva, Faculty of Medicine, Geneva, SwitzerlandGeneva Centre for Inflammation Research, Geneva, SwitzerlandBackgroundInterleukin-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.MethodsNaïve 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 Il18bp-tdTomato reporter knock-in mice. The incidence and severity of arthritis, including mRNA levels of different cytokines, were compared in IL-18BP or IL-18 knock-out (KO) mice and their WT littermates.ResultsIL-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.ConclusionAlthough 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1215364/fullStill’s diseaseK/BxN serum transfer-induced arthritisinterleukin-18interleukin-18 binding proteinrheumatoid arthritissystemic juvenile idiopathic arthritis |
| spellingShingle | Sebastien Fauteux-Daniel Sebastien Fauteux-Daniel Sebastien Fauteux-Daniel Laura M. Merlo Pich Laura M. Merlo Pich Laura M. Merlo Pich Charlotte Girard-Guyonvarc’h Charlotte Girard-Guyonvarc’h Charlotte Girard-Guyonvarc’h Assunta Caruso Assunta Caruso Assunta Caruso Emiliana Rodriguez Emiliana Rodriguez Emiliana Rodriguez Cem Gabay Cem Gabay Cem Gabay The role of interleukin-18 and interleukin-18 binding protein in K/BxN serum transfer-induced arthritis Frontiers in Immunology Still’s disease K/BxN serum transfer-induced arthritis interleukin-18 interleukin-18 binding protein rheumatoid arthritis systemic juvenile idiopathic arthritis |
| title | The role of interleukin-18 and interleukin-18 binding protein in K/BxN serum transfer-induced arthritis |
| title_full | The role of interleukin-18 and interleukin-18 binding protein in K/BxN serum transfer-induced arthritis |
| title_fullStr | The role of interleukin-18 and interleukin-18 binding protein in K/BxN serum transfer-induced arthritis |
| title_full_unstemmed | The role of interleukin-18 and interleukin-18 binding protein in K/BxN serum transfer-induced arthritis |
| title_short | The role of interleukin-18 and interleukin-18 binding protein in K/BxN serum transfer-induced arthritis |
| title_sort | role of interleukin 18 and interleukin 18 binding protein in k bxn serum transfer induced arthritis |
| topic | Still’s disease K/BxN serum transfer-induced arthritis interleukin-18 interleukin-18 binding protein rheumatoid arthritis systemic juvenile idiopathic arthritis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1215364/full |
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