Abstract
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.
Highlights
The active and extensive communication between the immune and central nervous system (CNS) is essential in maintaining homeostasis of the CNS and mediating the pathogenesis of neurological diseases
Extensive staining in naïve mouse brain tissue demonstrates that within the corpus callosum (CC) region, ST2 is surprisingly expressed by some astrocytes, with lower expression level observed in neuron cell bodies and microglia (Figure 4A)
IL-33 deficient mice have an uncontrolled surge of neuronal aging due to failed repair at middle age and develop neurodegeneration and late-onset Alzheimer’s disease (AD)-like symptoms in old age [18]. This is characterized by Tau deposition and heavy neuronal loss in both the cerebral cortex and the hippocampus and accompanied with cognition and memory impairment. These findings indicate a critical role for IL-33 in the maintenance and repair of aging and stressed neurons
Summary
The active and extensive communication between the immune and central nervous system (CNS) is essential in maintaining homeostasis of the CNS and mediating the pathogenesis of neurological diseases. Around 33% of isolated brain cells of naïve mouse are IL-33 positive [12] and its mRNA expression level is higher than any other tissues and organs tested [1] These findings together with the recent evidence of ST2 expression by CNS resident cells [13, 14] indicate a unique role for the IL-33/ST2 signaling pathway within the CNS. The expression pattern and cellular distribution of ST2 in CNS remains understudied and somewhat disputed, there has been some exciting progress in recent years identifying IL-33 target cells This has provided new insights into the functional mechanisms of the signaling pathway in CNS. Extensive staining in naïve mouse brain tissue demonstrates that within the CC region, ST2 is surprisingly expressed by some astrocytes, with lower expression level observed in neuron cell bodies and microglia (Figure 4A). In the inflammatory spinal cord of experimental autoimmune encephalomyelitis (EAE) mice, mRNA of St2 is shown to be increased [29] and the upregulation is predominantly in the lesion area in the white matter [29, 37]
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