Alzheimer's disease as an auto-innate immune pathology with potential cell trans-differentiation and enhanced trained immunity in 3xTg-AD mouse model DOI

Fatma Saaoud,

Lu Liu,

Keman Xu

et al.

Journal of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: unknown

Published: April 15, 2025

Background Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory impairment. Neuroinflammatory processes, mediated glial and immune cells, contribute to neuronal damage. Emerging evidence implicates innate mechanisms, including trained immunity cell trans-differentiation, in AD pathogenesis, though their roles remain unclear. Objective To investigate transcriptomic changes the 3xTg-AD mouse model, focusing on trans-differentiation mechanisms. Methods RNA-sequencing was performed brain tissue (cortex plus hippocampus) from 11-month-old female wild-type mice (n = 3/group). Differentially expressed genes (fold change > 1.5, p < 0.05) were identified followed bioinformatics knowledge-based profiling. Public datasets also analyzed. Results exhibited 316 upregulated 412 downregulated genes. Downregulated included those for blood-brain barrier protein, while related cerebrospinal fluid. Increased expression of proinflammatory markers, as well differentiation, proliferation, activation, adhesion. Upregulation associated with migration suggests potential role inflammation cellular plasticity. Additionally, involved inflammasome pathways, immunometabolism, upregulated. Mechanistically, these modulated knockdown promoter SET-7, overexpression inhibitor IL-37, knockout IL-1 receptor, caspase-1, pattern recognition receptor CD36. Conclusions The finding underscore AD, revealing mechanistic framework which danger-associated molecular patterns drive responses, plasticity offering therapeutic targets neuroinflammation reprograming.

Language: Английский

The role of immune checkpoints PD-1 and CTLA-4 in cardiovascular complications leading to heart failure DOI Creative Commons
Song Huang, Yu Kang, Ting Liu

et al.

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

Published: April 4, 2025

Immune checkpoints, such as PD-1 and CTLA-4, are crucial regulators of immune responses, acting gatekeepers to balance immunity against foreign antigens self-tolerance. These checkpoints play a key role in maintaining cardiac homeostasis by preventing immune-mediated damage critical organs like the heart. In this study, we explored involvement CTLA-4 cardiovascular complications, particularly atherosclerosis myocarditis, which can lead heart failure. We conducted comprehensive analysis using animal models clinical data assess effects checkpoint inhibition on function. Our findings indicate that disruption pathways exacerbates myocardial inflammation, accelerates atherosclerotic plaque formation, promotes development Additionally, observed these led increased infiltration T lymphocytes, higher levels pro-inflammatory cytokines, enhanced tissue damage. results suggest preserving health, their result severe toxicity. study emphasizes need for careful monitoring health patients undergoing inhibitor therapies.

Language: Английский

Citations

0
Alzheimer's disease as an auto-innate immune pathology with potential cell trans-differentiation and enhanced trained immunity in 3xTg-AD mouse model DOI

Fatma Saaoud,

Lu Liu,

Keman Xu

et al.

Journal of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: unknown

Published: April 15, 2025

Background Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory impairment. Neuroinflammatory processes, mediated glial and immune cells, contribute to neuronal damage. Emerging evidence implicates innate mechanisms, including trained immunity cell trans-differentiation, in AD pathogenesis, though their roles remain unclear. Objective To investigate transcriptomic changes the 3xTg-AD mouse model, focusing on trans-differentiation mechanisms. Methods RNA-sequencing was performed brain tissue (cortex plus hippocampus) from 11-month-old female wild-type mice (n = 3/group). Differentially expressed genes (fold change > 1.5, p < 0.05) were identified followed bioinformatics knowledge-based profiling. Public datasets also analyzed. Results exhibited 316 upregulated 412 downregulated genes. Downregulated included those for blood-brain barrier protein, while related cerebrospinal fluid. Increased expression of proinflammatory markers, as well differentiation, proliferation, activation, adhesion. Upregulation associated with migration suggests potential role inflammation cellular plasticity. Additionally, involved inflammasome pathways, immunometabolism, upregulated. Mechanistically, these modulated knockdown promoter SET-7, overexpression inhibitor IL-37, knockout IL-1 receptor, caspase-1, pattern recognition receptor CD36. Conclusions The finding underscore AD, revealing mechanistic framework which danger-associated molecular patterns drive responses, plasticity offering therapeutic targets neuroinflammation reprograming.

Language: Английский

Citations

0