Lamacchia, C, Palmer, G, Rodriguez, E, Martin, P, Vigne, S, Seemayer, CA, Talabot-Ayer, D, Towne, JE and Gabay, C (2013) The severity of experimental arthritis is independent of IL-36 receptor signaling - art. no. R38. ARTHRITIS RESEARCH & THERAPY.

Abstract

Introduction: Interleukin (IL)-36 refers to three related IL-1 family cytokines, IL-36 alpha, IL-36 beta, and IL-36 gamma, that bind to the IL-36 receptor (IL-36R). IL-36 exerts proinflammatory effects in skin and lung and stimulates T cell responses. In the present study, we examined the expression and function of IL-36R and its ligands in experimental arthritis.Methods: Collagen-induced arthritis (CIA), antigen-induced arthritis (AIA), and K/BxN serum transfer-induced arthritis were induced according to standard protocols. Messenger RNA levels for IL-36R and its ligands in the joints of mice with CIA were determined by RT-qPCR. Mice with CIA were injected with a blocking monoclonal anti-IL-36R, a blocking anti-IL-1RI, or their isotype-matched control antibodies at the time of arthritis onset. Anti-IL-36R or control antibodies were also injected at the time of AIA induction. Finally, IL-36R-deficient mice were examined in AIA and serum transfer-induced arthritis. The development and severity of arthritis were assessed by clinical and histological scoring.Results: IL-36R, IL-36Ra and IL-36 gamma mRNA were detected in the joints of mice with CIA, but their levels did not correlate with arthritis severity. As opposed to anti-IL-1RI antibody treatment, the injection of an anti-IL-36R antibody was devoid of effect on the development and severity of CIA. The severity of joint inflammation and structural damage in AIA was also unaltered by anti-IL-36R antibody treatment. Finally, the severity of AIA and K/BxN serum transfer-induced arthritis was similar in IL-36R-deficient and wild-type mice.Conclusions: The development and severity of experimental arthritis are independent of IL-36R signaling

Item Type:	Article
Additional Information:	pubid: 230 nvp_institute: NIBR contributor_address: Univ Hosp Geneva, Dept Internal Med, Div Rheumatol, CH-1211 Geneva 14, Switzerland, Univ Geneva, Sch Med, Dept Pathol Immunol, CH-1211 Geneva 14, Switzerland Cem.Gabay@hcuge.ch; Novartis Pharma AG, Translat Med, NIBR, CH-4002 Basel, Switzerland ; Amgen Inc, Dept Inflammat Res, Seattle, WA 98119 USA ; Univ Hosp Geneva, Dept Internal Med, Div Rheumatol, CH-1211 Geneva 14, Switzerland; Univ Geneva, Sch Med, Dept Pathol Immunol, CH-1211 Geneva 14, Switzerland; Gabay, C; Univ Hosp Geneva, Dept Internal Med, Div Rheumatol, 26 Ave Beau Sejour, CH-1211 Geneva 14, Switzerland
Date Deposited:	13 Oct 2015 13:12
Last Modified:	13 Oct 2015 13:12
URI:	https://oak.novartis.com/id/eprint/22039