The severity of experimental arthritis is independent of IL-36 receptor signaling

Céline Lamacchia,Cem Gabay,Jennifer E Towne,Christian A Seemayer,Gaby Palmer,Dominique Talabot-Ayer,Emiliana Rodriguez,Solenne Vigne,Praxedis Martin

doi:10.1186/ar4192

Abstract

IntroductionInterleukin (IL)-36 refers to three related IL-1 family cytokines, IL-36α, IL-36β, and IL-36γ, 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.MethodsCollagen-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.ResultsIL-36R, IL-36Ra and IL-36γ 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.ConclusionsThe development and severity of experimental arthritis are independent of IL-36R signaling.

Highlights

Interleukin (IL)-36 refers to three related IL-1 family cytokines, IL-36a, IL-36b, and IL-36g, that bind to the IL-36 receptor (IL-36R)
IL-36R, IL-36g and IL-36Ra mRNA levels did not correlate with disease severity, but were comparable to those found in normal skin, a tissue in which IL-36 has been previously reported to play a pathogenic role [11]
In agreement with previously published data, IL-1RI, IL-1b and IL-1 receptor antagonist (IL-1Ra) mRNAs were present in inflamed joints of mice with Collagen-induced arthritis (CIA) (Figure 1D-F) with a significant correlation between IL-1b mRNA levels and the severity of arthritis [31]

Summary

Introduction

Interleukin (IL)-36 refers to three related IL-1 family cytokines, IL-36a, IL-36b, and IL-36g, that bind to the IL-36 receptor (IL-36R). Seven novel IL-1 family members have been identified on the basis of their sequence homology, three-dimensional protein structure, gene location and receptor binding profile [1,2,3,4,5,6,7]. These proteins are termed IL-36Ra, IL-36a, IL-36b, IL-36g, IL-37, IL-38 and IL-33 (previously known as IL-1F5, IL1F6, IL-1F8, IL-1F9, IL-1F7, IL-1F10 and IL-1F11, respectively) [8].

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