Aging is associated with increased prevalence of axonal injuries characterized by poor regeneration and disability. However, the underlying mechanisms remain unclear. In our experiments, RNA sequencing of sciatic dorsal root ganglia (DRG) revealed significant aging-dependent enrichment in T cell signaling both before and after sciatic nerve injury (SNI) in mice. Lymphotoxin activated the transcription factor NF-κB, which induced expression of the chemokine CXCL13 by neurons. This in turn recruited CXCR5CD8 T cells to injured DRG neurons overexpressing major histocompatibility complex class I. CD8 T cells repressed the axonal regeneration of DRG neurons via caspase 3 activation. CXCL13 neutralization prevented CXCR5CD8 T cell recruitment to the DRG and reversed aging-dependent regenerative decline, thereby promoting neurological recovery after SNI. Thus, axonal regeneration can be facilitated by antagonizing cross-talk between immune cells and neurons.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1126/science.abd5926 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Insights and Interventions in Age-Associated Inflammation.
Curr Opin Genet Dev
January 2025
National Clinical Research Center for Geriatric Disorders, Aging Translational Medicine Center, International Center for Aging and Cancer, Xuanwu Hospital Capital Medical University, Beijing 100053, China; University of Chinese Academy of Sciences, Beijing, 100049, China; Aging Biomarker Consortium (ABC), Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, 100101, China; Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. Electronic address:
Aging is a systemic, complex, and heterogeneous process characterized by a progressive decline in physiological functions, rendering it a major risk factor for various chronic diseases. Chronic inflammation has emerged as both a hallmark and a driver in this complicated process. This persistent inflammatory state arises from a spectrum of stimuli, ranging from external pathogens to internal cellular remnants, to metabolic dysregulation, and to chronic stress.
View Article and Find Full Text PDFThe role of CXCL12/CXCR4/CXCR7 axis in cognitive impairment associated with neurodegenerative diseases.
Brain Behav Immun Health
February 2025
Pediatric and Urology and Regenerative Medicine Research Center, Gene, Cell and Tissue Research Institute, Children Medical Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Neurodegenerative diseases, including Alzheimer's Disease (AD), Parkinson's Disease (PD), Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS), are characterized by progressive neuronal loss and cognitive impairment (CI). The: Cysteine-X-cysteine chemokine ligand 12(CXCL12)/CXC chemokine receptor type 4 (CXCR4)/CXC chemokine receptor type 7 (CXCR7) axis has emerged as a critical molecular pathway in the development of CI in these disorders. This review explores the role of this axis in the pathogenesis of CI across these neurodegenerative diseases, synthesizing current evidence and its implications for targeted therapies.
View Article and Find Full Text PDFKIF9 Ameliorates Neuropathology and Cognitive Dysfunction by Promoting Macroautophagy in a Mouse Model of Alzheimer's Disease.
Aging Cell
January 2025
Growth, Development, and Mental Health of Children and Adolescence Center, Pediatric Research Institute, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder affecting the elderly. The imbalance of protein production and degradation processes leads to the accumulation of misfolded and abnormally aggregated amyloid-beta (Aβ) in the extracellular space and forms senile plaques, which constitute one of the most critical pathological hallmarks of AD. KIF9, a member of the kinesin protein superfamily, mediates the anterograde transport of intracellular cargo along microtubules.
View Article and Find Full Text PDFThe 2024 American Association for Thoracic Surgery expert consensus document: Current standards in donor lung procurement and preservation.
J Thorac Cardiovasc Surg
February 2025
Division of Thoracic Surgery, University of Toronto, Toronto, Ontario, Canada. Electronic address:
Background: Donor lung procurement and preservation is critical for lung transplantation success. Unfortunately, the large variability in techniques impacts organ utilization rates and transplantation outcomes. Compounding this variation, recent developments in cold static preservation and new technological advances with machine perfusion have increased the complexity of the procedure.
View Article and Find Full Text PDFNeuromodulatory Treatment for Dizziness and Chronic Neurological Dysfunction in an Elderly Patient Using Radio Electric Asymmetric Conveyer (REAC) Neuro Psycho Physical Optimization (NPPO) Gamma Brain Wave Optimization (BWO-G): A Case Report.
Cureus
January 2025
Department of Research, Department of Regenerative Medicine, Rinaldi Fontani Foundation, Florence, ITA.
An 88-year-old woman presented with a longstanding history of dizziness, tremors, and progressive mental and physical decline, significantly impairing her mobility and autonomy. Recently discharged from an ICU, the patient required extensive support for daily activities. Diagnostic evaluations, including EEG and analysis, revealed irregular frequency peaks and altered cortical activity, particularly in the frontal and prefrontal regions.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!