Investigation of autophagy irregularity in regulator T lymphocytes of ALS patients

ABSTRACT Objective: Neuroinflammation is a hallmark of amyotrophic lateral sclerosis (ALS). Regulatory T cells (Tregs) are essential in immune tolerance and prevention of neuroinflammation. It has been shown that a significant decrease in regulatory T cell and FoxP3 protein expression is observed in ALS patients. The primary cause of FoxP3+ regulatory T cell loss in ALS is unknown. In this study, the role of autophagy dysregulation in FoxP3+ regulatory T cells in ALS was investigated. Method: A total of 23 ALS patients and 24 healthy controls were included in the study. Mononuclear cells (MNCs) were obtained from peripheral blood, then regulatory T cells were isolated. Isolated regulatory T cells were stained with FoxP3 and LC3 antibodies and analyzed by flow cytometry to determine autophagy levels in FoxP3+ regulatory T cells 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). No significant association between ALSFRS-R decay rate and autophagy level in patients was found. Additionally, there was no significant difference between the autophagy levels in FoxP3+ regulatory T cells in patients with rapidly progressing ALS and in patients with slowly progresing ALS. Conclusion: Excessive levels of the autophagy in FoxP3+regulatory T cells in ALS patients could potentially be an explanation for increased cell death, worsening of neuroinflammation and could potentially have been a contributing factor to the initiation of the disease. However, disease progression cannot be attributed to the level of autophagy in FoxP3+ regulatory T cells. Key words: ALS, Regulatory T Cells, Autophagy, Neuroinflamation