Recent studies highlight the implication of innate and adaptive immunity in pathophysiology Alzheimer's disease, foster immunotherapy as a promising strategy for its treatment. Vaccines targeting amyloid-β peptide provided encouraging results mouse models, but severe side effects attributed to T cell responses first clinical trial AN1792 underlined need better understanding disease. We previously showed that regulatory cells critically control amyloid-β-specific CD4 + both physiological...

We recently demonstrated that stromal cell-derived factor-1 (SDF-1/CXCL12) forms complexes with CXCR4, but also syndecan-4 expressed by human primary lymphocytes and macrophages, HeLa cells. suggested behaves as a SDF-1-signaling molecule. Here, we demonstrate SDF-1 strongly accelerates the shedding of ectodomains to lesser extent syndecan-1 from The fact this acceleration was not inhibited CXCR4 antagonist AMD3100, anti-CXCR4 mAb 12G5, gene silencing suggests its CXCR4-independence....

Objective Recent studies have underlined the effect of systemic inflammation on pathophysiology Alzheimer's disease (AD). Neutrophils are key components early innate immunity and contribute to uncontrolled if not tightly regulated. The aim our study was fully characterize human circulating neutrophils at different stages in AD. Methods We analyzed neutrophil phenotypes functions 42 patients with AD (16 mild cognitive impairment 26 dementia), compared them 22 age‐matched healthy subjects....

Abstract In addition to their physiologic effects in inflammation and angiogenesis, chemokines are involved cancer pathology. The aim of this study was determine whether the chemokine stromal cell–derived factor 1 (SDF-1) induces growth, migration, invasion human hepatoma cells. We show that SDF-1 G protein–coupled receptor, (C-X-C motif) receptor 4 (CXCR4), mRNA expressed Huh7 cells, which secrete bind SDF-1. This binding depends on CXCR4 glycosaminoglycans. associates with CXCR4,...

To better understand the functional state of circulating neutrophils in patients with ischemic stroke (IS) for planning future clinical trials.We analyzed by flow cytometry activation and distribution neutrophil peripheral subsets 41 acute IS less than 6 hours before admission compared them 22 age-matched healthy controls.Our results demonstrated continuous basal hyperactivation during IS, characterized lower l-selectin expression higher CD11b at cell surface, increased ROS production...

Abstract Background A dysregulated immune response is emerging as a key feature of critical illness in COVID-19. Neutrophils are components early innate immunity that, if not tightly regulated, contribute to uncontrolled systemic inflammation. We sought decipher the role neutrophil phenotypes, functions, and homeostasis COVID-19 disease severity outcome. Methods By using flow cytometry, this longitudinal study compares peripheral whole-blood neutrophils from 90 ICU patients with those 22...

Increasing evidence supports a key role for peripheral immune processes in the pathophysiology of Alzheimer's disease (AD), highlighting an intricate interplay between brain resident glial cells and both innate adaptive effectors. We previously showed that regulatory T (Tregs) have beneficial impact on progression AD-like pathology, notably by modulating microglial response associated with Aβ deposits mouse model amyloid pathology. Besides microglia, reactive astrocytes also play critical...

Stromal cell-derived factor-1 (SDF-1)/CXCL12, the ligand for CXCR4, induces signal transduction. We previously showed that CXCL12 binds to high- and low-affinity sites expressed by primary cells cell lines, forms complexes with CXCR4 as expected also a proteoglycan, syndecan-4, but does not form syndecan-1, syndecan-2, CD44 or beta-glycan. demonstrated occurrence of CXCL12-independent heteromeric complex between syndecan-4. However, our data ruled out glycosaminoglycan-dependent binding HeLa...

ABSTRACT Growing evidence highlights sex‐related differences in the pathogenesis of Alzheimer's disease (AD). Yet, early impact sex on neuronal activity and microglia hippocampus, a main site memory formation one most vulnerable brain areas AD, remains poorly understood. We thus assessed these issues by using APPPS1 mouse model AD‐like amyloid pathology at pre‐symptomatic stage (5–6 months). Our electrophysiological data point to opposite alterations hippocampal CA1 neurons' basal...

Alzheimer's disease (AD) is an incurable, age-related and progressive neurodegenerative characterized by cognitive impairments. Deficits in synaptic plasticity were reported various models of AD-like pathology are considered as early contributing factor impairment. However, the majority previous studies focused on overt, symptomatic stages assessed long-term potentiation (LTP), whereas depression (LTD) was much less investigated precise nature its involvement remains poorly defined. To...

Active immunization against Aβ was reported to have a therapeutic effect in murine models of Alzheimer's disease. Clinical vaccination trial AN1792 interrupted due the development 6 % patients meningoencephalitis likely involving pro-inflammatory CD4+ T cells. However, potential implication auto-aggressive anti-Aβ CD8+ cells has been poorly investigated. Potential MHC-I-restricted Aβ-derived epitopes were first analyzed for their capacity recruit functional cell responses mouse models. Their...

In prion diseases, PrPc, a widely expressed protein, is transformed into pathogenic form called PrPSc, which in itself infectious. Antibodies directed against PrPc have been shown to inhibit PrPSc conversion vitro and protect vivo from disease. Other effectors with potential eliminate PrPSc-producing cells are cytotoxic T PrP-derived peptides but their ability or induce deleterious autoimmune reactions not known. The natural tolerance makes difficult raise efficient adaptive responses. To...

Several hurdles must be overcome in order to achieve efficient and safe immunotherapy against conformational neurodegenerative diseases. In prion diseases, the main difficulty is that protein tolerated as a self protein, which prevents powerful immune responses. Passive antibody therapy effective only during early, asymptomatic disease, well before diagnosis made. If of diseases achieved, it crucial understand precisely how tolerance can effector pathways may delay disease progression. To...

Background Acute ischemic stroke is a neurologic emergency associated with severe disability and death. There growing evidence that neutrophil extracellular traps (NETs) contribute to the pathogenesis of acute stroke. By mechanical removal occluding thrombus from patient's vasculature, endovascular thrombectomy enables collection material for immunohistologic analysis. The aim our study was strengthen association NET content in thrombi clinical outcome guide future therapeutics. Methods We...

There is to date no effective way of preventing or curing neurodegenerative diseases such as Alzheimer disease transmissible spongiform encephalopathies. The idea treating those conditions by immunological approaches has progressively emerged over the last ten years. Encouraging results have been reported in and peripheral forms mouse prion following passive injection Abs active immunization against peptides proteins presumably at origin disorders. Still, major difficulties persist due some...

Vaccines targeting amyloid-beta (Abeta) peptide represent promising therapeutic options for the treatment of Alzheimer's disease (AD). Active immunization against Abeta has emerged as a potential strategy that can prevent deposition and reverse cognitive decline in murine models. However, an vaccination trial (AN1792) human AD patients was prematurely interrupted due to occurrence meningoencephalitides 6% cases, supposedly related inappropriate activation Abeta-specific T cells. In contrast,...

Abstract Background Chronic innate neuroinflammation mediated by microglia and astrocytes in response to Aβ pathological Tau species is a cardinal feature of AD that contributes disease pathogenesis. Accumulating evidence now also highlight an instrumental role T cells peripheral‐central immune crosstalk the pathophysiology AD. Both preclinical clinical reports suggest potential therapeutic interest peripheral immunomodulatory approaches aimed at amplifying regulatory (Tregs), e.g. through...

Recent studies highlight the implication of innate and adaptive immunity in pathophysiology Alzheimer's disease (AD), foster immunotherapy as a promising strategy for its treatment. Vaccines targeting amyloid-beta (Abeta) peptide provided encouraging results mouse models, but severe side effects attributed to T cell responses first clinical trial AN1792 underlined need better understanding AD. We previously showed that regulatory cells (Tregs) critically control Abeta-specific CD4+T both...

Vaccines targeting beta-amyloid represent promising strategies for the treatment of AD. Immunization approaches provided encouraging results in mouse models and a subsequent human clinical trial (AN1792). Whereas preclinical studies murine did not show evidence T cell-related side effects, AN1792 had to be interrupted due development meningoencephalitis attributed pro-inflammatory cell responses 6% patients. Several reports also suggest that -specific CD4 + cells may implicated...

Abstract Background Increasing evidence support a key role of peripheral immune processes in the pathophysiology Alzheimer’s disease (AD), highlighting an intricate interplay between brain resident glial cells and both innate adaptive effectors. We previously showed that regulatory T (Tregs) have beneficial impact on progression AD‐like pathology, notably by modulating microglial response associated with Ab deposits mouse model amyloid pathology. Besides microglia, reactive astrocytes also...