1. IL-38 overexpression induces anti-inflammatory effects in mice arthritis models and in human macrophages in vitro
- Author
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Géraldine Bart, Benoit Le Goff, Pierre Layrolle, Cem Gabay, Frédéric Blanchard, Gaby Palmer, Aurélie Najm, Régis Brion, S Touchais, Valérie Trichet, Marie-Astrid Boutet, Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Equipe Labellisée LIGUE 2012 [Nantes], Service de rhumatologie [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Department of Pathology and Immunology [Geneva, Switzerland] (Clinical Pathology Division), University of Geneva [Switzerland]-Geneva University Hospitals - HUG [Switzerland], Division of Rheumatology [Geneva, Switzerland], Geneva University Hospital, Geneva-Department of Internal Medicine [Genève], This work was supported by Inserm and in part by the Arthritis Foundation and by the French Society of Rheumatology. M-AB was a recipient from a fellowship from the French Ministry of Research. CG is supported by grants from the Swiss National Science Foundation (310030_152638), the Rheumasearch Foundation, the Uniscientia Foundation and the Institute of Arthritis Research., maurice, sandrine, Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), and Université de Genève = University of Geneva (UNIGE)-Geneva University Hospitals - HUG [Switzerland]
- Subjects
Cartilage, Articular ,0301 basic medicine ,medicine.medical_treatment ,Arthritis ,Macrophages/immunology ,Interleukin-23 ,Arthritis, Rheumatoid ,Mice ,0302 clinical medicine ,Tumor Necrosis Factor-alpha/genetics/immunology ,Immunology and Allergy ,ddc:616 ,[SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system ,Interleukin-17 ,Synovial Membrane ,Interleukin ,Arthritis, Experimental/genetics/immunology ,Immunohistochemistry ,Interleukin-17/genetics/immunology ,3. Good health ,Synovial Membrane/cytology ,medicine.anatomical_structure ,Cytokine ,[SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system ,030220 oncology & carcinogenesis ,Rheumatoid arthritis ,Cytokines ,Tumor necrosis factor alpha ,Arthritis, Rheumatoid/immunology ,Blotting, Western ,Immunology ,Enzyme-Linked Immunosorbent Assay ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,In Vitro Techniques ,Real-Time Polymerase Chain Reaction ,Bone and Bones ,Interleukin-6/genetics/immunology ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,Proinflammatory cytokine ,03 medical and health sciences ,Rheumatology ,Fibroblasts/immunology ,medicine ,Animals ,Humans ,Th17 Cells/immunology ,[SDV.BC] Life Sciences [q-bio]/Cellular Biology ,Inflammation ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,business.industry ,Interleukins ,Macrophages ,Cartilage ,Bone and Bones/diagnostic imaging ,X-Ray Microtomography ,Fibroblasts ,Interleukins/genetics/immunology ,medicine.disease ,Arthritis, Experimental ,Cartilage, Articular/diagnostic imaging ,030104 developmental biology ,Interleukin-23/genetics/immunology ,Cell culture ,Culture Media, Conditioned ,Th17 Cells ,Transcriptome ,business - Abstract
International audience; OBJECTIVES:Interleukin (IL)-38 is a newly characterised cytokine that belongs to the IL-1 family. This cytokine is expressed in the rheumatoid arthritis (RA) synovial tissue and IL-38 deficient mice have exacerbated arthritis. Here, we analysed the effect of IL-38 overexpression in the joints of arthritic mice, in human macrophages and synovial fibroblasts in vitro.METHODS:Articular injections of an adeno-associated virus (AAV) 2/8 encoding IL-38 were performed in collagen-induced arthritis (CIA), K/BxN serum transfer-induced arthritis (STIA) and antigen-induced arthritis (AIA) in mice. The effect of IL-38 overexpression was evaluated through clinical scores, immunohistochemistry, microCT, Luminex and RT-qPCR analysis. THP-1 macrophages were transduced with a lentiviral vector to overexpress IL-38.RESULTS:Clinical inflammatory scores were significantly decreased after AAV IL-38 injection in joints of mice with CIA and STIA, but not AIA. This decrease was accompanied by reduced macrophage infiltration and a decreased expression of Th17 cytokines (IL-17, IL-23, IL-22) and TNFα. However, IL-38 overexpression had no effect on cartilage or bone destruction. In vitro, the THP-1 monocytic cell line expressed less IL-6, TNFα and IL-23 after IL-38 overexpression. Conditioned media from these cells, containing released IL-38, also exert an anti-inflammatory effect on human primary macrophages and synovial fibroblasts from patients with RA.CONCLUSIONS:This study shows for the first time that IL-38 overexpression attenuates the severity of experimental arthritis. IL-38 may exert its anti-inflammatory effects by decreasing the production of proinflammatory cytokines by macrophages and synovial fibroblasts. This effect can lead to the development of novel treatment strategies in arthritis.
- Published
- 2017