SenNet recommendations for detecting senescent cells in different tissues

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(12), P. 1001 - 1023

Published: June 3, 2024

Language: Английский

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p16-dependent increase of PD-L1 stability regulates immunosurveillance of senescent cells

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(8), P. 1336 - 1345

Published: Aug. 1, 2024

The accumulation of senescent cells promotes ageing and age-related diseases, but molecular mechanisms that use to evade immune clearance accumulate in tissues remain be elucidated. Here we report p16-positive upregulate the checkpoint protein programmed death-ligand 1 (PD-L1) chronic inflammation. We show p16-mediated inhibition cell cycle kinases CDK4/6 induces PD-L1 stability via downregulation its ubiquitin-dependent degradation. p16-expressing alveolar macrophages elevate promote an immunosuppressive environment can contribute increased burden cells. Treatment with activating anti-PD-L1 antibodies engaging Fcγ receptors on effector leads elimination Our study uncovers a mechanism p16-dependent regulation reveals potential targeting improve immunosurveillance ameliorate senescence-associated

Language: Английский

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Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 7, 2025

Abstract Macrophages are immune cells belonging to the mononuclear phagocyte system. They play crucial roles in defense, surveillance, and homeostasis. This review systematically discusses types of hematopoietic progenitors that give rise macrophages, including primitive progenitors, erythro-myeloid stem cells. These have distinct genetic backgrounds developmental processes. Accordingly, macrophages exhibit complex diverse functions body, phagocytosis clearance cellular debris, antigen presentation, response, regulation inflammation cytokine production, tissue remodeling repair, multi-level regulatory signaling pathways/crosstalk involved homeostasis physiology. Besides, tumor-associated a key component TME, exhibiting both anti-tumor pro-tumor properties. Furthermore, functional status is closely linked development various diseases, cancer, autoimmune disorders, cardiovascular disease, neurodegenerative metabolic conditions, trauma. Targeting has emerged as promising therapeutic strategy these contexts. Clinical trials macrophage-based targeted drugs, immunotherapies, nanoparticle-based therapy were comprehensively summarized. Potential challenges future directions targeting also been discussed. Overall, our highlights significance this versatile cell human health which expected inform research clinical practice.

Language: Английский

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The neuroimmune connectome in health and disease

Nature, Journal Year: 2025, Volume and Issue: 638(8050), P. 333 - 342

Published: Feb. 12, 2025

Language: Английский

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Psychedelic control of neuroimmune interactions governing fear

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: April 23, 2025

Language: Английский

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Senescent brain cell types in Alzheimer's disease: Pathological mechanisms and therapeutic opportunities

Neurotherapeutics, Journal Year: 2025, Volume and Issue: 22(3), P. e00519 - e00519

Published: Jan. 6, 2025

Cellular senescence is a cell state triggered by programmed physiological processes or cellular stress responses. Stress-induced senescent cells often acquire pathogenic traits, including toxic secretome and resistance to apoptosis. When form faster than they are cleared the immune system, accumulate in tissues throughout body contribute age-related diseases, neurodegeneration. This review highlights evidence of brain their role Alzheimer's disease (AD), leading cause dementia older adults. We also discuss progress challenges senotherapies, pharmacological strategies clear mitigate effects, which hold promise as interventions for AD related dementias (ADRD).

Language: Английский

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Long-term outcome and prognosis of mixed histiocytosis (Erdheim-Chester disease and Langerhans Cell Histiocytosis)

EClinicalMedicine, Journal Year: 2024, Volume and Issue: 73, P. 102658 - 102658

Published: May 27, 2024

Language: Английский

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Macrophage-derived PDGF-BB modulates glycolytic enzymes expression and pyroptosis in nucleus pulposus cells via PDGFR-β/TXNIP pathway

Osteoarthritis and Cartilage, Journal Year: 2024, Volume and Issue: 32(10), P. 1245 - 1260

Published: May 12, 2024

Language: Английский

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A Trisomy 21-linked Hematopoietic Gene Variant in Microglia Confers Resilience in Human iPSC Models of Alzheimer’s Disease

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 14, 2024

SUMMARY While challenging, identifying individuals displaying resilience to Alzheimer’s disease (AD) and understanding the underlying mechanism holds great promise for development of new therapeutic interventions effectively treat AD. Down syndrome (DS), or trisomy 21, is most common genetic cause Interestingly, some people with DS, despite developing AD neuropathology, show cognitive decline. Furthermore, DS are at an increased risk myeloid leukemia due somatic mutations in hematopoietic cells. Recent studies indicate that cells may lead neurodegeneration. Microglia, derived from lineages, play a central role etiology. We therefore hypothesize microglia carrying associated impart Using CRISPR-Cas9 gene editing, we introduce 21-linked hotspot CSF2RB A455D mutation into human pluripotent stem cell (hPSC) lines both healthy individuals. Employing hPSC-based vitro culture vivo chimeric mouse brain models, response pathological tau, suppresses microglial type-1 interferon signaling, independent 21 background. This reduces neuroinflammation enhances phagocytic autophagic functions, thereby ameliorating senescent dystrophic phenotypes microglia. Moreover, promotes unique subcluster tissue repair properties. Importantly, provide protection neuronal function, such as neurogenesis synaptic plasticity brains where largely repopulate hippocampus. When co-transplanted same brains, phagocytize replace wildtype following tau treatment. Our findings suggest hPSC-derived could be employed develop effective replacement therapy other age-related neurodegenerative diseases, even without need deplete endogenous diseased prior transplantation.

Language: Английский

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Aging and neurodegeneration: when systemic dysregulations affect brain macrophage heterogeneity

The Journal of Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

Microglia, the major population of brain resident macrophages, differentiate from yolk sac progenitors in embryo and play multiple nonimmune roles organization throughout development life. Various microglia subtypes have been described by transcriptomic proteomic signatures, involved metabolic pathways, morphology, intracellular complexity, time residency, ontogeny, both disease settings. Such macrophage heterogeneity increases with aging or neurodegeneration. Monocytes' infiltration differentiation into monocyte-derived macrophages (MDMs) contribute to this diversity. Microbiota's role diseases has recently highlighted, revealing how microbial signals, such as metabolites, influence MDMs. In brief review, we describe these signals can through their sensome shape MDMs bone marrow brain. Monocytes could then be a crucial player constitution dysbiotic gut-brain axis neurodegenerative aging.

Language: Английский

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