Autophagy dysregulation plays a crucial role in regulatory T-cell loss and neuroinflammation in amyotrophic lateral sclerosis (ALS)


Azad A., Gökmen Ü. R., UYSAL H., KÖKSOY S., BİLGE U., MANGUOĞLU A. E.

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, vol.25, no.3-4, pp.336-344, 2024 (SCI-Expanded) identifier identifier

Abstract

Objective: Neuroinflammation is the hallmark of amyotrophic lateral sclerosis (ALS) disease. Regulatory T cells (Tregs) are essential in immune tolerance and neuroinflammation prevention. It has been shown that a significant decrease in Treg and FoxP3 protein expression is observed in ALS patients. The main reason for the FoxP3+ Treg loss in ALS is unknown. In this study, the role of autophagy dysregulation in FoxP3+ Tregs in ALS was investigated. Methods: Twenty-three ALS patients and 24 healthy controls were recruited for the study. Mononuclear cells (MNCs) were obtained from peripheral blood, and then Tregs were isolated. Isolated Tregs were stained with FoxP3 and LC3 antibodies and analyzed in flow cytometry to determine autophagy levels in FoxP3+ Tregs in patients and controls. Results: The mean of FoxP3+ LC3+ cells, were 0.47 and 0.45 in patients and controls, respectively. The mean of FoxP3+ LC3− cells was 0.15 in patients and 0.20 in controls, p = 0.030 (p < 0.05). There is no significant correlation between ALSFRS-R decay rate and autophagy level in patients. Also, there is no significant difference between autophagy levels in FoxP3+ Tregs in patients with rapidly progressing ALS and slow-progressing ALS. Conclusion: Excessive autophagy levels in FoxP3+ Tregs in ALS patients can potentially be an explanation for an increased cell death and result in worsened neuroinflammation and disease onset. However, the disease progress is not attributable to autophagy levels in FoxP3+ Tregs.