Abstract
IntroductionInterleukin (IL)-33 is a cytokine of the IL-1 family, which signals through the ST2 receptor. Previous work suggested implication of the IL-33/ST2 axis in the pathogenesis of human and mouse arthritis. Here, we directly investigated the role of endogenous IL-33 in K/BxN serum transfer-induced arthritis by using IL-33 knockout (KO) mice.MethodsArthritis was induced by injection of complete K/BxN serum or purified IgG. Disease severity was monitored by clinical and histological scoring.ResultsK/BxN serum transfer induced pronounced arthritis with similar incidence and severity in IL-33 KO and wild-type (WT) mice. In contrast, disease development was significantly reduced in ST2 KO mice. IL-33 expression in synovial tissue was comparable in arthritic WT and ST2 KO mice, and absent in IL-33 KO mice. Transfer of purified arthritogenic IgG instead of complete K/BxN serum also resulted in similar arthritis severity in IL-33 KO and WT mice, excluding a contribution of IL-33 contained in the serum of donor mice to explain this result. We investigated additional potential confounding factors, including purity of genetic background, but the mechanisms underlying reduced arthritis in ST2 KO mice remained unclear.ConclusionsThe data obtained with IL-33 KO mice indicate that endogenous IL-33 is not required for the development of joint inflammation in K/BxN serum transfer-induced arthritis. On the contrary, arthritis severity was reduced in ST2 KO mice. This observation might relate to IL-33 independent effects of ST2, and/or reveal the existence of confounding variables affecting the severity of joint inflammation in these KO strains.
Highlights
Interleukin (IL)-33 is a cytokine of the IL-1 family, which signals through the ST2 receptor
On day 6 after induction of arthritis, serum IL-33 levels were similar in WT and ST2 KO mice (WT, mean: 310 ± 192 pg/ml, range < 1.61 to 1258 pg/ml; ST2KO, 447 ± 287 pg/ml, range < 1.61 to 2142 pg/ml) and comparable to IL-33 levels measured in naïve WT C57BL/6 mice (n = 17; 294 ± 191 pg/ml, range < 1.61 to 3062 pg/ml) housed in our conventional mouse facility
Our results indicate that, IL-33 is expressed in the synovium during K/BxN serum transfer-induced arthritis, IL-33 KO mice display similar arthritis severity as compared to WT controls, suggesting that endogenous IL-33 is not required for the development of joint inflammation in this experimental model
Summary
Interleukin (IL)-33 is a cytokine of the IL-1 family, which signals through the ST2 receptor. Interleukin (IL)-33 is the most recently discovered member of the IL-1 cytokine family (see [1] for review). IL-33, like IL-1a, is a dual-function protein, displaying both nuclear and extracellular effects. The latter are mediated by its binding to an IL-1 receptor family member called ST2 (IL1RL1). The long signaling ST2 receptor isoform (ST2l) is expressed in many hematopoietic cells, including a number of innate immune cells, which are involved in T helper 2 (Th2)-type response. Injection of recombinant IL-33 induces or amplifies type 2 immune effects in different mouse models [4,5,6].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
