MOLECULAR AND CELLULAR MECHANISMS MEDIATED BY DENDRITIC CELLS INVOLVED IN THE INDUCTION OF TOLERANCE

Abstract

Autoimmune diseases and complications after transplantation operations are major public health problem, as they often lead to deterioration in the quality of life, reduce work capacity and disability in the population. To date, the induction of antigen-specific tolerance is the promising method of therapy. During this process dendritic cells play important role. In this review current data of tolerogenic dendritic cells characterization, of factors inducing tolerogenic properties in dendritic cells, development of central and peripheral tolerance by dendritic cells, role of tolerogenic dendritic cells in the formation of regulatory B cells, molecular and cellular mechanisms that are involved in the formation of an immunological tolerance depending on tolerogenic dendritic cells were analyzed. Tolerogenic dendritic cells play a key role in maintaining of immune homeostasis by inducing immunological tolerance mechanisms which are associated with the generation of regulatory T cells, induction of anergy or apoptosis of T cells. Formation of tolerogenic properties in dendritic cells is occurred by various factors that regulate the maturation and differentiation of dendritic cells and induce anti-inflammatory agents synthesis of them. Because of their ability to induce natural and peripheral regulatory T cells, dendritic cells contribute to the development of the central and peripheral tolerance in the organism. Analysis of the results of experimental work demonstrates that in addition to induction of regulatory T cells tolerogenic dendritic cells participate in generating of regulatory B cells that play a role in the formation of tolerance and have the ability to affect the population of regulatory T cells. However, the mechanisms that lead to the formation of B cell population by tolerogenic dendritic cells have not been completely established yet. Review of published data showed that the molecular and cellular mechanisms of immunological tolerance induction by tolerogenic dendritic cells and other regulatory cell subpopulations interacting with each other are similar to a large extent. Currently, the role of tolerogenic dendritic cells in maintaining of immune tolerance is determined generally, however, some aspects require further investigation. Subsequent experimental studies will lead to a better understanding of the signaling mechanisms and the realization of immunological functions of tolerogenic dendritic cells, which provide additional information for application approaches development of tolerogenic dendritic cells for the control of autoimmune diseases and transplant complications.

Keywords

• tolerogenic dendritic cells
• immunological tolerance
• central tolerance
• peripheral tolerance
• regulatory t cells
• regulatory b cells