Project description:The role of IL-5 in brain neuroimmunity remains unknown. We investigated the role of IL-5 in cognitive function in aged mice. We examined the transcriptomes of sorted microglia and brain T cells from aged mice treated with PBS or IL-5.
Project description:Spinal cord injured mice were treated with IL-13, IL-4 or PBS. Populations of macrophages and microglia were sorted and analyzed separately.
Project description:ILC2 are potent producers of IL-5 and IL-13 and Th2 cytokines have been found to promote neurogenesis and cognitive functions. We report microglia, brain T cells and ILC2 have a range of differentially expressed genes in IL-33 treated aged mice. Brain ILC2 upregulated a range of neuroprotective genes.
Project description:Microglia are important immune cells in the brain. Microglia undergo a series of alterations during aging and increase the susceptibility to brain dysfunctions. However, the characteristics of microglia during the aging process are not fully understood. In this study, we mapped transcriptional and epigenetic profiles of microglia from 3- to 24-month-old mice. We observed unexpected gender divergences and identified age-dependent microglia (ADEM) genes in the aging process. We then compared characteristics between microglial aging and activation. To dissect the function of aged microglia excluding the influence from other aged brain cells, we established an accelerated microglial turnover model without directly affecting other brain cells. By this model, we achieved aged microglia in non-aged brains and confirmed that aged microglia per se contribute to cognitive decline. Collectively, we provide a comprehensive resource to decode the aging process of microglia, shedding light on how microglia maintain brain functions.
Project description:Aging is the predominant risk factor for neurodegenerative diseases. One key phenotype as brain ages is the aberrant innate immune response characterized by proinflammation. However, the molecular mechanisms underlying aging-associated proinflammation are poorly defined. Whether chronic inflammation plays a causal role in cognitive decline in aging and neurodegeneration has not been established. Here we established a mechanistic link between chronic inflammation and aging microglia, and demonstrated a causal role of aging microglia in neurodegenerative cognitive deficits. Expression of microglial SIRT1 reduces with the aging of microglia. Genetic reduction of microglial SIRT1 elevates IL-1β selectively, and exacerbates cognitive deficits in aging and in transgenic mouse models of frontotemporal dementia (FTD). Interestingly, the selective activation of IL-1β transcription by SIRT1 deficiency is likely mediated through hypomethylating the proximal promoter of IL-1β. Consistent with our findings in mice, selective hypomethylation of IL-1β at two CpG sites are found in normal aging humans and demented patients with tauopathy. Our findings reveal a novel epigenetic mechanism in aging microglia that contributes to cognitive deficits in neurodegenerative diseases. Study of changes related to alterations of SIRT1 levels in microglia of young and aged animals and in models of neurodegenerative dementia
Project description:The experiment is to demonstrate the global m6A methylation signatures and their correlation with mRNA expression patterns in microglia stimulated by LPS. The results also identified m6A modifiers with significantly altered expression, which reveals the key one that regulate the m6A modifications in microglia.
Project description:ILC2 are potent producers of IL-5 and IL-13 and Th2 cytokines. We have found that they promote neurogenesis and cognitive functions in aged mice . We report that CP and meningeal ILC2 from IL-33 treated aged mice have differential expression of Th2 cytokines as well as genes involved in metabolism through scRNA-sequencing.
Project description:Aging induces cognitive decline and Th2 cytokines have been found to promote neurogenesis and cognitive functions. ILC2 are potent producers of IL-5 and IL-13. The role of ILC2 in cognitive function in the context of aging has not been investigated. We report tissue resident ILC2 accumulate in the choroid plexus of the brain in aged mice. They are long-lived and can switch between cellular dormancy and proliferation in response to replication stress. ILC2 play a direct role in promoting the cognitive functions in aged mice, through producing IL-5. IL-5 has neuroprotective functions including neurogenesis and reducing pro-inflammatory functions of microglia in aged mice.