title: Deficiency in IL-1 Receptor Type 2 Aggravates K/BxN Serum Transfer-Induced Arthritis in Mice but Has No Impact on Systemic Inflammatory Responses.
abstract: The biological activity of IL-1 is tightly regulated by the specific receptor antagonist (IL-1Ra) and the decoy receptor IL-1 receptor type 2 (IL-1R2). The role of IL-1Ra has been well demonstrated in IL-1Ra-deficient mice. In contrast, the role of endogenous IL-1R2 remains widely unknown. To define the functional role of endogenous IL-1R2 in the K/BxN serum transfer arthritis model and in IL-1β- or LPS-induced systemic inflammation in vivo, IL-1R2-/-mice were created and compared with wild type mice. IL-1R2-/-mice bred habitually and exhibited a normal phenotype. IL-1R2 deficiency aggravated arthritis severity and increased mRNA levels for key cytokines and chemokines such as IL-6, IL-1β, Cxcl-1, and Cxcl-2 significantly in ankles. There was no effect of IL-1R2 deficiency on the cell-autonomous cytokine response to IL-1β in the tested cell types, i.e., neutrophils, macrophages, and fibroblasts, but IL-1R2 deficiency on neutrophils increased the IL-1-induced response of fibroblasts in trans. Furthermore, IL-1β induced shedding of IL-1R2 in vivo. Inflammatory responses to IL-1β and LPS-induced mortality were not different in IL-1R2-/-compared with wild type mice. Our data demonstrate that the decoy receptor IL-1R2 plays an important inhibitory role in local IL-1- and neutrophil-dependent tissue inflammation as shown in the K/BxN serum transfer arthritis model. In contrast to IL-1Ra, IL-1R2 appears to be less crucial for systemic responses to acute administration of IL-1 or LPS.
authors.affiliation: Department of Pathology and Immunology, School of Medicine, University of Geneva, 1211 Geneva 4, Switzerland.|Division of Rheumatology, University Hospital of Geneva, 1211 Geneva 4, Switzerland; and.
authors.forename: Praxedis
authors.initials: P
authors.lastname: Martin
authors.affiliation: Department of Pathology and Immunology, School of Medicine, University of Geneva, 1211 Geneva 4, Switzerland.|Division of Rheumatology, University Hospital of Geneva, 1211 Geneva 4, Switzerland; and.
authors.forename: Gaby
authors.initials: G
authors.lastname: Palmer
authors.affiliation: Department of Pathology and Immunology, School of Medicine, University of Geneva, 1211 Geneva 4, Switzerland.|Division of Rheumatology, University Hospital of Geneva, 1211 Geneva 4, Switzerland; and.
authors.forename: Emiliana
authors.initials: E
authors.lastname: Rodriguez
authors.affiliation: Global Clinical Science and Epidemiology, Actelion Pharmaceuticals Ltd., 4123 Allschwil, Switzerland.
authors.forename: Christian Alexander
authors.initials: CA
authors.lastname: Seemayer
authors.affiliation: Department of Pathology and Immunology, School of Medicine, University of Geneva, 1211 Geneva 4, Switzerland.|Division of Rheumatology, University Hospital of Geneva, 1211 Geneva 4, Switzerland; and.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Palomo
authors.affiliation: Department of Pathology and Immunology, School of Medicine, University of Geneva, 1211 Geneva 4, Switzerland.|Division of Rheumatology, University Hospital of Geneva, 1211 Geneva 4, Switzerland; and.
authors.forename: Dominique
authors.initials: D
authors.lastname: Talabot-Ayer
authors.affiliation: Department of Pathology and Immunology, School of Medicine, University of Geneva, 1211 Geneva 4, Switzerland; cem.gabay@hcuge.ch.|Division of Rheumatology, University Hospital of Geneva, 1211 Geneva 4, Switzerland; and.
authors.forename: Cem
authors.identifier: 0000-0001-6853-3063
authors.initials: C
authors.lastname: Gabay
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D053574:Receptors, Interleukin-1 Type II / Q000276:immunology*
chemical_list: D053574:Receptors, Interleukin-1 Type II