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Review
. 2015 Mar;20(3):263-72.
doi: 10.1007/s10495-015-1090-8.

How apoptotic β-cells direct immune response to tolerance or to autoimmune diabetes: a review

Marta Vives-Pi  1 , Silvia Rodríguez-Fernández, Irma Pujol-Autonell
Affiliations
Review

How apoptotic β-cells direct immune response to tolerance or to autoimmune diabetes: a review

Marta Vives-Pi et al. Apoptosis. 2015 Mar.

Abstract

Type 1 diabetes (T1D) is a metabolic disease that results from the autoimmune attack against insulin-producing β-cells in the pancreatic islets of Langerhans. Currently, there is no treatment to restore endogenous insulin secretion in patients with autoimmune diabetes. In the last years, the development of new therapies to induce long-term tolerance has been an important medical health challenge. Apoptosis is a physiological mechanism that contributes to the maintenance of immune tolerance. Apoptotic cells are a source of autoantigens that induce tolerance after their removal by antigen presenting cells (APCs) through a process called efferocytosis. Efferocytosis will not cause maturation in dendritic cells, one of the most powerful APCs, and this process could induce tolerance rather than autoimmunity. However, failure of this mechanism due to an increase in the rate of β-cells apoptosis and/or defects in efferocytosis results in activation of APCs, contributing to inflammation and to the loss of tolerance to self. In fact, T1D and other autoimmune diseases are associated to enhanced apoptosis of target cells and defective apoptotic cell clearance. Although further research is needed, the clinical relevance of immunotherapies based on apoptosis could prove to be very important, as it has translational potential in situations that require the reestablishment of immunological tolerance, such as autoimmune diseases. This review summarizes the effects of apoptosis of β-cells towards autoimmunity or tolerance and its application in the field of emerging immunotherapies.

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Figures

Fig. 1
Fig. 1
Schematic representation of β-cells apoptosis and efferocytosis in type 1 diabetes. β-cells that undergo apoptosis are recognized and phagocytosed by APCs, leading to physiologic tolerance induction. However, an increase in the rate of β-cells apoptosis rate and/or defects in efferocytosis result in the activation of APCs, contributing to inflammation, to the lack of tolerance to self and to autoimmune disease. Strategies of immunointervention based on apoptosis, such as apoptotic cell administration or tolDCs-pulsed with apoptotic β-cells- could help to the reestablishment of immunological tolerance to β-cells autoantigens, lost in type 1 diabetes
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