This study examined the biologic responses of transgenic mice expressing human leukocyte antigen (HLA)-DR3 and human CD4 molecules, in the absence of murine major histocompatibility complex (MHC) class II molecules (Ab(0)), to staphylococcal enterotoxins (SEs) and evaluated protective immunity of a nonsuperantigen form of SEB against wild-type holotoxin. HLA-DR3 transgenic mice responded to several log lower concentrations of SEs and secreted higher levels of proinflammatory cytokines than did wild-type mice. Vaccination of transgenic mice with a nonsuperantigenic form of SEB induced high levels of neutralizing anti-SEB antibodies, which protected the mice from a surge in proinflammatory cytokine secretion after SEB challenge. The humanlike responses of the transgenic mice to SEs support the hypothesis that these mice represent an appropriate model to examine vaccines and therapeutics against SEs. This is thought to be the first report of examination of a vaccine against SEB in the context of human MHC class II receptors.
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http://dx.doi.org/10.1086/340828 | DOI Listing |
Front Neurosci
December 2024
Institute of Reconstructive Neurobiology, Medical Faculty and University Hospital of Bonn, University of Bonn, Bonn, Germany.
Brain aging is a chronic process linked to inflammation, microglial activation, and oxidative damage, which can ultimately lead to neuronal loss. Sialic acid-binding immunoglobulin-like lectin-11 (SIGLEC-11) is a human lineage-specific microglial cell surface receptor that recognizes -2-8-linked oligo-/polysialylated glycomolecules with inhibitory effects on the microglial inflammatory pathways. Recently, the gene locus was prioritized as a top tier microglial gene with potential causality to Alzheimer's disease, although its role in inflammation and neurodegeneration remains poorly understood.
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
January 2025
Department of Psychology, University of Miami, Coral Gables, FL, United States.
The neuropeptide oxytocin (OXT) and its receptor (OXTR) have been shown to play an important role in glucose metabolism, and pancreatic islets express this ligand and receptor. In the current study, OXTR expression was identified in α-, β-, and δ-cells of the pancreatic islet by RNA hybridization, and OXT protein expression was observed only in β-cells. In order to examine the contribution of islet OXT/OXTR in glycemic control and islet β-cell heath, we developed a β-cell specific OXTR knock-out (β-KO) mouse.
View Article and Find Full Text PDFFront Neural Circuits
January 2025
Department of Molecular and Cellular Physiology, Shinshu University School of Medicine, Matsumoto, Japan.
Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social interaction and communication, along with restricted and repetitive behaviors. Both genetic and environmental factors contribute to ASD, with prenatal exposure to valproic acid (VPA) and nicotine being linked to increased risk. Impaired adult hippocampal neurogenesis, particularly in the ventral region, is thought to play a role in the social deficits observed in ASD.
View Article and Find Full Text PDFGBA is the major risk gene for Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB), two common α-synucleinopathies with cognitive deficits. We investigated the role of mutant GBA in cognitive decline by utilizing Gba (L444P) mutant, SNCA transgenic (tg), and Gba-SNCA double mutant mice. Notably, Gba mutant mice showed early cognitive deficits but lacked PD-like motor deficits or α-synuclein pathology.
View Article and Find Full Text PDFUnlabelled: The T cell receptor (TCR) repertoire of intestinal CD4+ T cells is enriched for specificity towards microbiome-encoded epitopes shared among many microbiome members, providing broad microbial reactivity from a limited pool of cells. These cells actively coordinate mutualistic host-microbiome interactions, yet many epitopes are shared between gut symbionts and closely related pathobionts and pathogens. Given the disparate impacts of these agents on host health, intestinal CD4+ T cells must maintain strain-level discriminatory power to ensure protective immunity while preventing inappropriate responses against symbionts.
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