Pathogenic Microglia Orchestrate Neurotoxic Properties of Eomes-Expressing Helper T Cells.

In addition to disease-associated microglia (DAM), microglia with MHC-II and/or IFN-I signatures may form additional pathogenic subsets that are relevant to neurodegeneration. However, the significance of such MHC-II and IFN-I signatures remains elusive. We demonstrate here that these microglial subsets play intrinsic roles in orchestrating neurotoxic properties of neurotoxic Eomes Th cells under the neurodegeneration-associated phase of experimental autoimmune encephalomyelitis (EAE) that corresponds to progressive multiple sclerosis (MS).

FMRP, FXR1 protein and Dlg4 mRNA, which are associated with fragile X syndrome, are involved in the ubiquitin-proteasome system.

The ubiquitin-proteasome system (UPS) is a proteolytic pathway that is essential for life maintenance and vital functions, and its disruption causes serious impairments, e.g., disease development.

Characterization of Astrocytes in the Minocycline-Administered Mouse Photothrombotic Ischemic Stroke Model.

Astrocytes, together with microglia, play important roles in the non-infectious inflammation and scar formation at the brain infarct during ischemic stroke. After ischemia occurs, these become highly reactive, accumulate at the infarction, and release various inflammatory signaling molecules. The regulation of astrocyte reactivity and function surrounding the infarction largely depends on intercellular communication with microglia.

Eggshell membrane modulates gut microbiota to prevent murine pre-cachexia through suppression of T helper cell differentiation.

Background: Cachexia is a life-threatening condition observed in several pathologies, such as cancer or chronic diseases. Interleukin 10 (Il10) gene transfer is known to improve cachexia by downregulating Il6. Here, we used an IL10-knockout mouse model to simulate cachexia and investigate the effects of eggshell membrane (ESM), a resistant protein, on general pre-cachexia symptoms, which is particularly important for the development of cachexia therapeutics.

Immune-mediated neurodegenerative trait provoked by multimodal derepression of long-interspersed nuclear element-1.

Neurodegeneration is a process involving both cell autonomous and non-cell autonomous neuron loss, followed by a collapse of neural networks, but its pathogenesis is poorly understood. We have previously demonstrated that Eomes-positive helper T (Eomes + Th) cells recognizing LINE-1(L1)-derived prototypic antigen ORF1 mediate neurotoxicity associated with the neurodegenerative pathology of experimental autoimmune encephalomyelitis (EAE). Here, we show that Eomes + Th cells accumulate in the CNS of mouse models of authentic neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD), and secrete the neurotoxic granzyme B after encounter with ORF1 antigen.