CD22 modulation alleviates amyloid β-induced neuroinflammation

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: Feb. 5, 2025

Neuroinflammation is a crucial driver of multiple neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and Parkinson's (PD). Yet, therapeutic targets for diseases based on neuroinflammation still warrant investigation. CD22 has been implicated in neuroinflammatory namely AD. Specifically, plasma soluble (sCD22) level upregulated patients with Direct experimental evidence the role needed, as better understanding its impact microglia activation potential. Here we reported that sCD22 promotes both vivo vitro. activated via p38 ERK1/2 signaling pathway secretion TNFα, IL-6 CCL3. Moreover, sialic acid binding domain 2,6 linked glycan sCD22. The pivotal potential targeting was demonstrated Amyloid β (Aβ) induced-neuroinflammation hCD22 transgenic mice. Suciraslimab improved working memory resolved vivo. Further, membrane inhibited induced-NFκB mechanistic study delineated suciraslimab suppressed Aβ-induced IL-1β human PBMC. also IL-12 IL-23 reduced surface expression α4 integrin B cells. Intriguingly, discovered interact Aβ enhanced internalization CD22-Aβ complex microglia. Our data highlights importance driving dual mechanism to resolve inflammation promote phagocytosis.

Language: Английский

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Targeting macrophages in cancer immunotherapy: Frontiers and challenges

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Cancer immunotherapy has emerged as a groundbreaking approach in cancer treatment, primarily realized through the manipulation of immune cells, notably T cell adoption and checkpoint blockade. Nevertheless, cells encounters formidable hurdles. Macrophages, serving pivotal link between innate adaptive immunity, play crucial roles phagocytosis, cytokine secretion, antigen presentation. Consequently, macrophage-targeted therapies have garnered significant attention. We aim to provide most cutting-edge insights future perspectives for therapies, fostering development novel effective treatments. To date, forefront strategies macrophage targeting encompass: altering their plasticity, harnessing CAR-macrophages, phagocytosis checkpoints. Macrophages are characterized by remarkable diversity offering unique therapeutic target. In this context, we critically analyze innovative aimed at transforming macrophages from M2 (tumor-promoting) M1 (tumor-suppressing) phenotype. Furthermore, delve into design principles, developmental progress, advantages CAR-macrophages. Additionally, illuminate challenges encountered checkpoints on propose potential overcome these obstacles.

Language: Английский

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CD300LF⁺ microglia impede the neuroinflammation following traumatic brain injury by inhibiting STING pathway

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(7)

Published: July 1, 2024

The diversity in microglial phenotypes and functions following traumatic brain injury (TBI) is poorly characterized. aim of this study was to explore precise targets for improving the prognosis TBI patients from a perspective.

Language: Английский

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The dual role of microglia in intracerebral hemorrhage

Behavioural Brain Research, Journal Year: 2024, Volume and Issue: 473, P. 115198 - 115198

Published: Aug. 10, 2024

Language: Английский

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Pterostilbene improves neurological dysfunction and neuroinflammation after ischaemic stroke via HDAC3/Nrf1-mediated microglial activation

Cellular & Molecular Biology Letters, Journal Year: 2024, Volume and Issue: 29(1)

Published: Aug. 28, 2024

Stroke is a type of acute brain damage that can lead to series serious public health challenges. Demonstrating the molecular mechanism stroke-related neural cell degeneration could help identify more efficient treatment for stroke patients. Further elucidation factors regulate microglia and nuclear factor (erythroid-derived 2)-like 1 (Nrf1) may promising strategy treating neuroinflammation after ischaemic stroke. In this study, we investigated possible role pterostilbene (PTS) in Nrf1 regulation animal models ischaemia

Language: Английский

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CpG and Rutin Co‐Loaded DNA Tetrahedra for Targeted Therapy of Intracerebral Hemorrhage: Synergistic Hematoma Clearance and Neuroinflammation Inhibition

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: unknown

Published: April 26, 2024

Abstract Intracerebral hemorrhage (ICH) presents a formidable challenge due to its high mortality and disability rates, primarily attributed cerebral hematoma formation ensuing neuroinflammation. Swift removal is paramount for prognosis, yet existing interventions carry risks limitations. Notably, elevated CD47 expression on hematoma‐associated RBC triggers “don't eat me” signal, impeding clearance, while microglial/macrophage erythrophagocytosis exacerbates oxidative stress the lysate evokes To address this conundrum, multifunctional nanomedicine (TD‐CFR), employing DNA tetrahedra (TD) as carrier ICH treatment introduced. The investigations reveal that CpG enhances phagocytosis of CD47‐expressing by microglia/macrophages via lipid metabolism modulation. Integration into TD preserves pro‐phagocytic efficacy, TD's double‐stranded region enables efficient encapsulation Rutin, potent anti‐inflammatory antioxidant flavonoid. Capitalizing disrupted blood‐brain barrier integrity at site, TD‐CFR achieves robust enrichment within post‐intravenous administration, augmented folate receptor‐mediated targeting microglia/macrophages. Efficacy assessments in mouse rabbit models confirm TD‐CFR's therapeutic benefits, including neuroinflammation suppression, brain function restoration. Leveraging biosafety profile dual active ingredient loading capacity, study unveils promising drug paradigm ICH.

Language: Английский

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Extracellular Vesicles From Bone Marrow‐Derived Macrophages Enriched in ARG1 Enhance Microglial Phagocytosis and Haematoma Clearance Following Intracerebral Haemorrhage

Journal of Extracellular Vesicles, Journal Year: 2025, Volume and Issue: 14(1)

Published: Jan. 1, 2025

ABSTRACT Microglial phagocytosis of haematomas is crucial for neural functional recovery following intracerebral haemorrhage (ICH), a process regulated by various factors from within and outside the central nervous system (CNS). Extracellular vesicles (EVs), significant mediators intercellular communication, have been demonstrated to play pivotal role in pathogenesis progression CNS diseases. However, regulatory endogenous EVs on phagocytic capacity microglia post‐ICH remains elusive. Utilising multi‐omics analysis brain tissue‐derived proteomics single‐cell RNA sequencing, this study identified that bone marrow‐derived macrophages (BMDMs) potentially enhance microglial via ICH. By blocking BMDMs reducing ARG1 BMDM‐derived EVs, we facilitate erythrophagocytosis delivering post‐ICH. EVs‐carried was found augment promoting RAC1‐dependent cytoskeletal remodelling microglia. Collectively, research uncovers an communication pathway mediated This provides novel paradigm EV‐mediated mechanisms suggests promising therapeutic potential treatment

Language: Английский

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CD22 exacerbates brain injury in subarachnoid hemorrhage by inhibiting microglial phagocytic function

Neurological Research, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 11

Published: Feb. 15, 2025

Introduction Subarachnoid hemorrhage (SAH) is a neurological emergency with high mortality rate. The phagocytic and homeostatic functions of microglial cells play crucial role after SAH. This study aims to investigate the mechanism CD22-mediated abnormal phagocytosis in brain injury caused by

Language: Английский

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Immune cells in intracerebral hemorrhage

Brain Hemorrhages, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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A new perspective on the regulation of neuroinflammation in intracerebral hemorrhage: mechanisms of NLRP3 inflammasome activation and therapeutic strategies

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 27, 2025

Intracerebral hemorrhage (ICH), a specific subtype within the spectrum of stroke disorders, is characterized by its high mortality and significant risk long-term disability. The initiation progression neuroinflammation play central critical role in pathophysiology ICH. NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, protein complex involved initiating inflammation, focus this article. Microglia astrocytes roles inflammatory damage process associated with neuroinflammation. NLRP3 inflammasome expressed both types glial cells, activation drives these cells toward pro-inflammatory phenotype, which exacerbates brain. However, regulatory relationship between two cell remains to be explored. Targeting inflammasomes microglia or may provide an effective approach mitigate following This article first provides overview composition mechanisms inflammasome. Subsequently, it summarizes recent research findings on novel signaling pathways that regulate activity. Finally, we reviewed progress inhibitors, highlighting clinical translation potential certain candidates. These inhibitors hold promise as innovative strategies for managing inflammation

Language: Английский

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