Innate immune memory is a vital mechanism of myeloid cell plasticity that occurs in response to environmental stimuli and alters subsequent immune responses. Two types of immunological imprinting can be distinguished—training and tolerance. These are epigenetically mediated and enhance or suppress subsequent inflammation, respectively. Whether immune memory occurs in tissue-resident macrophages in vivo and how it may affect pathology remains largely unknown. Here we demonstrate that peripherally applied inflammatory stimuli induce acute immune training and tolerance in the brain and lead to differential epigenetic reprogramming of brain-resident macrophages (microglia) that persists for at least six months. Strikingly, in a mouse model of Alzheimer's pathology, immune training exacerbates cerebral beta-amyloidosis and immune tolerance alleviates it; similarly, peripheral immune stimulation modifies pathological features after stroke. Our results identify immune memory in the brain as an important modifier of neuropathology. Overall design: mRNA was isolated from FACS-purified microglia and prepared for RNA-sequencing.
Innate immune memory in the brain shapes neurological disease hallmarks.
Sex, Specimen part, Treatment, Subject
View SamplesOsteoarthritic cartilage has largely been investigated, however supporting structures as the acetabular labrum are less investigated. In this studies we aimed to identify differences in gene expression between healthy and osteoarthritic labrum cells
Distinct dysregulation of the small leucine-rich repeat protein family in osteoarthritic acetabular labrum compared to articular cartilage.
Specimen part, Subject
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