Type 1 diabetes and tolerogenic dendritic cells: toward the prevention and cure of the disease

Type 1 Diabetes (T1D) is an autoimmune disease characterized by beta cell destruction leading to high blood glucose. Type 1 Diabetes (T1D) results from poorly defined interactions between susceptibility genes, the environment, and the immune system. It is initiated by a combination of susceptibility genes that create a setting in which an environmental trigger can launch the autoimmune process. The immune system attacks and destroys the insulin-producing beta cells of the pancreas, causing the complete loss of insulin production. Dendritic cells are a specialized lineage of cells for presenting antigen to naive or quiescent cells, having immunomodulatory properties. Dendritic cells are derived from hemopoietic bone marrow progenitor cells. These progenitor cells initially transform into immature dendritic cells. These cells are characterized by high endocytic activity and low T-cell activation potential. Immature dendritic cells constantly sample the surrounding environment for pathogens. This is probably done through many molecular pathways like the pattern recognition receptors (PRRs) and the Toll-like receptors (TLRs). Once they have come into contact with a presentable antigen, they become activated into mature dendritic cells and present the antigen at their cell surface using MHC molecules. Simultaneously, they upregulate cell-surface receptors that act as coreceptors in T-cell activation such as CD80, CD86 and others, enhancing their ability to activate T-cells. Modulating dendritic cell function can modulate the immune system balance. Inducing tolerogenic dendritic cells can be a way to prevent and/or cure immune disorders. Tolerogenic dendritic cells are less effective in T cell activation. A lower T cell response to specific antigens may be the key to cure some diseases, type 1 Diabetes included. The balance of the immune system is a complex mechanism involving many molecules and cells, some of them probably still unknown. In a well functioning immune system there are not only T cells able to fight against antigens but also T cells able to regulate the activity of the other T cell subsets, the regulatory T cells. Tolerogenic dendritic cells have less power to activate T cells against antigens, while having the power to stimulate regulatory T cells making them instrumental in the balance of tolerance in two ways: lowering T cell stimulation and stimulating higher T cell suppression by the regulatory T cells. This leads to a lower immune response to antigens. Indeed, the generation of tolerogenic dendritic cells may be a key for the prevention and cure in Type 1 Diabetes. Many chemicals (aspirin, vitamin D, Aloe Vera) are able to modulate dendritic cells activity and their T cells interaction. PDL1, the Programmed Death Ligand 1 or B7H1 is a new member of the B7 family that can interact with PD1, a putative negative regulator for immune function, encoded by Pdcd1. PDL1 may be a key in Type 1 Diabetes. Pathogenesis of Type 1 Diabetes involves genetic, environmental and immunological factors. As many factors are involved, many points could be targets for therapy. Targets involved in blocking and/or modulating the immune response should be explored for the protection of the residual beta cell mass and the regeneration of the insulin producing cells. Many studies have been performed focusing on individual pathogenetic steps by many scientists around the world. While it is extremely useful to study each step separately for a better understanding of the mechanisms of the disease, only a combo therapy having as targets each one of the altered mechanisms could lead to a cure for Type 1 Diabetes. So, as Type 1 Diabetes is a complex disease involving many different altered molecular mechanisms, only a combo therapy could have significance in finding a cure for Type 1 Diabetes.