IL‐33 attenuates EAE by suppressing IL‐17 and IFN‐γ production and inducing alternatively activated macrophages

Abstract

Interleukin (IL)- [26] and is a proinflammatory cytokine in CIA [14,27]. Recent studies have also shown that the IL-33/ST2 pathway plays a significant role in the amplification of M2 polarization and chemokine production, which contribute to innate and antigen-induced airway inflammation [28] and protect against obesity-related metabolic events [29].Interestingly, the highest levels of IL-33 expression in naïve mice are found in the brain and spinal cord [15], indicating that IL-33 may have CNS-specific functions in addition to its role in immune modulation. Astrocytes express both and the expression of IL-33 in the CNS was increased in response to inflammatory stimuli [31]. Recently, it was also reported that IL-33 levels were elevated in the periphery and CNS of MS patients, implicating IL-33 in the pathogenesis of MS [32]. However, the precise role of IL-33 and its receptor in CNS under healthy and inflammatory conditions remain unclear.In the present study, we show that ST2 1C). Quantitative PCR analysis confirmed the upregulation of ST2 expression in Fig. 1B as it clearly shows the enhanced expression of ST2 mRNA in the CNS of mice with EAE compared with that of the naïve mice (Fig. 1D). ST2 −/− mice developed exacerbated EAETo identify an endogenous role of IL-33 in EAE, we next investigated the development of EAE in ST2 −/− mice. EAE was induced in C57BL/6 WT and ST2 −/− mice, Fig. 2A shows that the ST2 −/− mice developed more severe EAE than that in the WT mice. In agreement with many previous reports, BALB/c mice are resistant to the induction of EAE. However ST2 −/− BALB/c mice developed a mild but clearly detectable EAE while the WT BALB/c controls did not (Fig. 2B), the observation was further confirmed by histological analysis of the CNS tissues at day 19 after immunization ( Fig. 2C). Minimal leukocyte infiltration was found in the CNS of WT BALB/c mice whereas significant leukocyte infiltration was found in the submeningeal infiltration in the CNS tissues of ST2 −/− BALB/c mice ( Fig. 2C). IL-33 treatment attenuates EAE developmentWe next investigated the effect of exogenous IL-33 in the development of EAE. C57BL/6 mice were immunized as described in was injected intraperitoneally to each mouse daily from day 12 to day 20 after immunization. Both groups of mice developed similar degree of EAE from day 10 to day 15. However, from day 15, mice treated with IL-33 recovered significantly faster than the control mice treated with PBS ( Fig. 3A). In induced experimental autoimmune diseases, disease severity could vary between experiments even with the same protocol. Analysis using multiple comparisons suggests that the effect of IL-33 treatment on the outcome of EAE mice could be time revealed marked reduction of infiltrating cells in the spinal cord tissues of IL-33-treated mice (Fig. 3B). Importantly, IL-33 had no effect on the disease development in ST2 −/− C57BL/6 mice ( Fig. 3C) demonstrating the specificity of the IL-33 effect. IL-33 alters the cytokine production of EAE miceTo investigate the i...

Soluble ST2 as a marker of disease activity in systemic juvenile idiopathic arthritis

“…In this study, serum sST2 levels in patients with s-JIA were elevated not only in the active phase but also in the inactive phase. These findings indicate that sST2 may have a role in resolving inflammatory responses by promoting monocyte differentiation into M2 macrophages through Th2 immune responses in the pathogenesis of s-JIA, as previously reported [16,28].…”

Protection in antibody- and T cell-mediated autoimmune diseases by antiinflammatory IgG Fcs requires type II FcRs

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Nitric Oxide–Induced Regulatory T Cells Inhibit Th17 but Not Th1 Cell Differentiation and Function

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