Sera of Neuromyelitis Optica Patients Increase BID-Mediated Apoptosis in Astrocytes

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(13), P. 7117 - 7117

Published: June 27, 2022

Neuromyelitis optica (NMO) is a rare disease usually presenting with bilateral or unilateral optic neuritis simultaneous sequential transverse myelitis. Autoantibodies directed against aquaporin-4 (AQP4-IgG) are found in most patients. They believed to cross the blood−brain barrier, target astrocytes, activate complement, and eventually lead astrocyte destruction, demyelination, axonal damage. However, it still not clear what primary pathological event is. We hypothesize that interaction of AQP4-IgG astrocytes leads DNA damage apoptosis. studied effect sera from seropositive NMO patients healthy controls (HCs) on astrocytes’ immune gene expression viability. led higher apoptosis-related genes, including BH3-interacting domain death agonist (BID), which significant differentiating (p < 0.0001), triggered more apoptosis compared HCs. Furthermore, increased immunological genes interact BID (TLR4 NOD-1). Our findings suggest might cause astrocytic It may be one mechanisms implicated provide new avenues for therapeutic intervention.

Language: Английский

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Immune–stem cell crosstalk in the central nervous system: how oligodendrocyte progenitor cells interact with immune cells

Immunology and Cell Biology, Journal Year: 2022, Volume and Issue: 101(1), P. 25 - 35

Published: Nov. 25, 2022

The interaction between immune and stem cells has proven essential for homeostasis regeneration in a wide range of tissues. However, because the central nervous system was long considered an immune-privileged organ, its immune-stem cell axis not deeply investigated until recently. Research shown that oligodendrocyte progenitor (OPCs), highly abundant population adult brain cells, establish bidirectional interactions with system. Here, we provide overview OPCs have tissue-resident recruited paying particular attention to role they play myelin neuroinflammation. We highlight described as key active players neuroinflammation, overriding previous concept are mere recipients signals. Understanding mechanisms behind this holds great potential development novel therapeutic approaches limiting neuroinflammation promoting repair. A better understanding system's will also be tackling two important features shared across neurodegenerative diseases, loss.

Language: Английский

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Targeting CNS myeloid infiltrates provides neuroprotection in a progressive multiple sclerosis model

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 122, P. 497 - 509

Published: Aug. 23, 2024

Demyelination and axonal injury in chronic-progressive Multiple Sclerosis (MS) are presumed to be driven by a neurotoxic bystander effect of meningeal-based myeloid infiltrates. There is an unmet clinical need attenuate disease progression such forms CNS-compartmentalized MS. The failure systemic immune suppressive treatments has highlighted the for neuroprotective repair-inducing strategies. Here, we examined whether direct targeting CNS cells modulating their toxicity may prevent irreversible tissue chronic immune-mediated demyelinating disease. To that end, utilized experimental autoimmune encephalomyelitis (EAE) model Biozzi mice, clinically relevant MS model. We continuously delivered intracerebroventricularly (ICV) retinoic acid receptor alpha agonist (RARα), as potent regulator cells, phase EAE. assessed severity performed pathological evaluations, functional analyses single-cell RNA sequencing on isolated spinal CD11b+ cells. Although initiating treatment disease, RARα successfully improved outcomes prevented loss. ICV inhibited pro-inflammatory pathways shifted toward phenotypes without affecting peripheral infiltrating cell phenotypes, or immunity. regulated cell-death across multiple populations suppressed apoptosis, resulting paradoxically marked increased neuroinflammatory infiltrates, consisting mainly microglia / border-associated macrophages. This work establishes notion neurotoxicity infiltrates Furthermore, it shows compartmentalized neuroinflammation selective regulation survival reduces injury, serve novel disease-modifying approach.

Language: Английский

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Repair what is lost: Neuroprotection through neural stem cells in progressive MS

Cell Reports Medicine, Journal Year: 2023, Volume and Issue: 4(3), P. 100985 - 100985

Published: March 1, 2023

Genchi et al.1 report the first phase 1 trial of neural stem cell transplantation in multiple sclerosis showing a reduction gray matter atrophy. Results give hope for new era induced neuroprotection, especially progressive sclerosis.

Language: Английский

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A protective effect of lower MHC-II expression in MOGAD

Journal of Neuroimmunology, Journal Year: 2024, Volume and Issue: 391, P. 578351 - 578351

Published: April 26, 2024

Language: Английский

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