Current advances in using tolerogenic dendritic cells as a therapeutic alternative in the treatment of type 1 diabetes

Abstract

Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing β-cells of the pancreatic islets by autoreactive T cells, leading to high blood glucose levels and severe long-term complications. The typical treatment indicated in T1D is exogenous insulin administration, which controls glucose levels; however, it does not stop the autoimmune process. Various strategies have been implemented aimed at stopping β-cell destruction, such as cellular therapy. Dendritic cells (DCs) as an alternative in cellular therapy have gained great interest for autoimmune disease therapy due to their plasticity to acquire immunoregulatory properties both in vivo and in vitro, performing functions such as anti-inflammatory cytokine secretion and suppression of autoreactive lymphocytes, which are dependent of their tolerogenic phenotype, displayed by features such as semimature phenotype, low surface expression of stimulatory molecules to prime T cells, as well as the elevated expression of inhibitory markers. DCs may be obtained and propagated easily in optimal amounts from peripheral blood or bone marrow precursors, such as monocytes or hematopoietic stem cells, respectively; therefore, various protocols have been established for tolerogenic (tol)DCs manufacturing for therapeutic research in the treatment of T1D. In this review, we address the current advances in the use of tolDCs for T1D therapy, encompassing protocols for their manufacturing, the data obtained from preclinical studies carried out, and the status of clinical research evaluating the safety, feasibility, and effectiveness of tolDCs.

Keywords: Type 1 diabetes, Dendritic cells, Autoimmunity, Immune tolerance, Cell therapy, Immunotherapy.

Core Tip: Autoimmunity in type 1 diabetes (T1D) is severe and leads to pancreatic dysfunction; therefore, therapies that can lessen this process are required. Cell therapy with tolerogenic dendritic cells (tolDCs) is a promising strategy. Various protocols have been implemented for tolDC generation, using stimuli such as cytokines, growth factors, and drugs. These cells are also subjected to treatments with antisense oligonucleotides, liposomes, toll-like receptor ligands, and peptides of the pancreatic islets, for optimization as T1D immunotherapy. Preclinical and clinical trials have demonstrated effectiveness of tolDC-based therapy. This review aims to give a detailed understanding of current advances in tolDC-based T1D treatment.