Interleukin (IL)‐33, a member of the IL‐1 cytokine family, is an important modulator of the immune system associated with several immune‐mediated disorders. High levels of IL‐33 are expressed by the central nervous system (CNS) suggesting a potential role of IL‐33 in autoimmune CNS diseases. We have investigated the expression and function of IL‐33 in the development of experimental autoimmune encephalomyelitis (EAE) in mice. We report here that IL‐33 and its receptor ST2 (IL‐33Rα) are highly expressed in spinal cord tissue, and ST2 expression is markedly increased in the spinal cords of mice with EAE. Furthermore, ST2‐deficient (ST2^−/−) mice developed exacerbated EAE compared with wild‐type (WT) mice while WT, but not ST2^−/− EAE mice treated with IL‐33 developed significantly attenuated disease. IL‐33‐treated mice had reduced levels of IL‐17 and IFN‐γ but produced increased amounts of IL‐5 and IL‐13. Lymph node and splenic macrophages of IL‐33‐treated mice showed polarization toward an alternatively activated macrophage (M2) phenotype with significantly increased frequency of MR⁺PD‐L2⁺ cells. Importantly, adoptive transfer of these IL‐33‐treated macrophages attenuated EAE development. Our data therefore demonstrate that IL‐33 plays a therapeutic role in autoimmune CNS disease by switching a predominantly pathogenic Th17/Th1 response to Th2 activity, and by polarization of anti‐inflammatory M2 macrophages.

Significant advances have been made in developing microfluidic polymerase chain reaction (PCR) devices in the last two decades. More recently, microfluidic microdroplet technology has been exploited to perform PCR in droplets because of its unique features. For example, it can prevent crossover contamination and PCR inhibition, is suitable for single-cell and single-molecule analyses, and has the potential for system integration and automation. This review will therefore focus on recent developments on droplet-based continuous-flow microfluidic PCR, and the major research challenges. This paper will also discuss a new way of on-chip flow control and a rational design simulation tool, which are required to underpin fully integrated and automated droplet-based microfluidic systems. We will conclude with a scientific speculation of future autonomous scientific discoveries enabled by microfluidic microdroplet technologies.

Interleukin-33 (IL-33) is a well-recognized immunomodulatory cytokine which plays critical roles in tissue function and immune-mediated diseases. The abundant expression of IL-33 in brain and spinal cord prompted many scientists to explore its unique role in the central nervous system (CNS) under physiological and pathological conditions. Indeed emerging evidence from over a decade's research suggests that IL-33 acts as one of the key molecular signaling cues coordinating the network between the immune and CNS systems, particularly during the development of neurological diseases. Here, we highlight the recent advances in our knowledge regarding the distribution and cellular localization of IL-33 and its receptor ST2 in specific CNS regions, and more importantly the key roles IL-33/ST2 signaling pathway play in CNS function under normal and diseased conditions.

Recent research findings have provided convincing evidence indicating a role for Interleukin-33 (IL-33) signalling pathway in a number of central nervous system (CNS) diseases including multiple sclerosis (MS) and Alzheimer’s disease. However, the exact function of IL-33 molecule within the CNS under normal and pathological conditions is currently unknown. In this study, we have mapped cellular expression of IL-33 and its receptor ST2 by immunohistochemistry in the brain tissues of MS patients and appropriate controls; and investigated the functional significance of these findings in vitro using a myelinating culture system. Our results demonstrate that IL-33 is expressed by neurons, astrocytes and microglia as well as oligodendrocytes, while ST2 is expressed in the lesions by oligodendrocytes and within and around axons. Furthermore, the expression levels and patterns of IL-33 and ST2 in the lesions of acute and chronic MS patient brain samples are enhanced compared with the healthy brain tissues. Finally, our data using rat myelinating co-cultures suggest that IL-33 may play an important role in MS development by inhibiting CNS myelination.

Interleukin‐33 (IL‐33) is associated with several important immune‐mediated disorders. However, its role in uveitis, an important eye inflammatory disease, is unknown. Here, we investigated the function of IL‐33 in the development of experimental autoimmune uveitis (EAU). IL‐33 and IL‐33 receptor (ST2) were expressed in murine retinal pigment epithelial (RPE) cells in culture, and IL‐33 increased the expression of Il33 and Mcp1 mRNA in RPE cells. In situ, IL‐33 was highly expressed in the inner nuclear cells of the retina of naïve mice, and its expression was elevated in EAU mice. ST2‐deficient mice developed exacerbated EAU compared with WT mice, and administration of IL‐33 to WT mice significantly reduced EAU severity. The attenuated EAU in IL‐33‐treated mice was accompanied by decreased frequency of IFN‐γ⁺ and IL‐17⁺ CD4⁺ T cells and reduced IFN‐γ and IL‐17 production but with increased frequency of IL‐5⁺ and IL‐4⁺ CD4 T cells and IL‐5 production in the draining lymph node and spleen. Macrophages from the IL‐33‐treated mice show a significantly higher polarization toward an alternatively activated macrophage phenotype. Our results therefore demonstrate that the endogenous IL‐33/ST2 pathway plays an important role in EAU, and suggest that IL‐33 represents a potential option for treatment of uveitis.