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

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.

Keywords:

• ALS
• regulatory T cells
• autophagy
• neuroinflammation

Acknowledgment

The authors thank the patients who participated in this research.

Authors’ contribution

AA designed the study, had a major role in data acquisition and preparation, interpreted the data and drafted the manuscript for intellectual content. URG had a major role in data acquisition. HU had a major role in clinical assessment and revised the manuscript for intellectual content. SK had a major role major role in data acquisition and interpretation. UB had a major role in statistical evaluation of the data and revised the manuscript for intellectual content. AEM designed and conceptualized the study and revised the manuscript for intellectual content.

Declaration of interest

All authors declare that they have no conflicts of interest.

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was supported by The Scientific and Technological Research Council of Turkey (TÜBİTAK) under Grant number 120S781; Akdeniz University, scientific research projects unit (BAP) under Grant TDK-2019-4715.