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J Immunol. 2017 Apr 1;198(7):2916-2926. doi: 10.4049/jimmunol.1600855. Epub 2017 Feb 24.

Deficiency in IL-1 Receptor Type 2 Aggravates K/BxN Serum Transfer-Induced Arthritis in Mice but Has No Impact on Systemic Inflammatory Responses.

Author information

1
Department of Pathology and Immunology, School of Medicine, University of Geneva, 1211 Geneva 4, Switzerland.
2
Division of Rheumatology, University Hospital of Geneva, 1211 Geneva 4, Switzerland; and.
3
Global Clinical Science and Epidemiology, Actelion Pharmaceuticals Ltd., 4123 Allschwil, Switzerland.
4
Department of Pathology and Immunology, School of Medicine, University of Geneva, 1211 Geneva 4, Switzerland; cem.gabay@hcuge.ch.

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.

PMID:
28235865
DOI:
10.4049/jimmunol.1600855
[Indexed for MEDLINE]
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