From islet transplantation to beta-cell regeneration: an update on beta-cell-based therapeutic approaches in type 1 diabetes.

INTRODUCTION: Type 1 diabetes (T1D) mellitus is an autoimmune disease in which immune cells, predominantly effector T cells, destroy insulin-secreting beta-cells. Beta-cell destruction led to various consequences ranging from retinopathy and nephropathy to neuropathy. Different strategies have been developed to achieve normoglycemia, including exogenous glucose compensation, whole pancreas transplantation, islet transplantation, and beta-cell replacement. AREAS COVERED: The last two decades of experience have shown that indigenous glucose compensation through beta-cell regeneration and protection is a peerless method for T1D therapy. Tremendous studies have tried to find an unlimited source for beta-cell regeneration, on the one hand, and beta-cell protection against immune attack, on the other hand. Recent advances in stem cell technology, gene editing methods, and immune modulation approaches provide a unique opportunity for both beta-cell regeneration and protection. EXPERT OPINION: Pluripotent stem cell differentiation into the beta-cell is considered an unlimited source for beta-cell regeneration. Devising engineered pancreas-specific regulatory T cells using Chimeric Antigen Receptor (CAR) technology potentiates an effective immune tolerance induction for beta-cell protection. Beta-cell regeneration using pluripotent stem cells and beta-cell protection using pancreas-specific engineered regulatory T cells promises to develop a curative protocol in T1D.

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

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.