Abstract
Dendritic cells (DCs), the most important professional antigen-presenting cells (APC), play crucial role in both immunity and tolerance. It is well known that DCs are able to mount immune responses against foreign antigens and simultaneously tolerate self-antigens. Since DCs can be modulated depending on the surrounding microenvironment, they can act as a bridge between innate and adaptive immunity. However, the mechanisms that support this dual role are not entirely clear. Recent studies have shown that DCs can be manipulated ex vivo in order to trigger their tolerogenic profile, what can be a tool to be used in clinical trials aiming the treatment of various diseases and the prevention of transplant rejection. In this sense, the blockage of costimulatory molecules on DC, in the attempt of inhibiting the second signal in the immunological synapse, can be considered as one of the main strategies under development. This review brings an update on current therapies using tolerogenic dendritic cells modulated with costimulatory blockers with the aim of reducing transplant rejection. However, although there are current clinical trials using tolerogenic DC to treat allograft rejection, the actual challenge is to modulate these cells in order to maintain a permanent tolerogenic profile.
Highlights
The main goal of a successful transplant is to promote immune tolerance of the transplanted organ or tissue, allowing the reestablishment of normal physiological functions, without generating damage to the recipient or to the transplanted tissue
It is known that a successful transplant relies on a deep understanding of the immune system allied with the balance and maintenance of effector and regulatory immune mechanisms [1, 4]
In the attempt of modulating the activity of Dendritic cells (DCs) on the treatment of autoimmunity, hypersensibility, and transplant rejection, many researchers aim to develop therapies based on tolerogenic DC
Summary
The main goal of a successful transplant is to promote immune tolerance of the transplanted organ or tissue, allowing the reestablishment of normal physiological functions, without generating damage to the recipient or to the transplanted tissue. Thereby, the relationship between tolerance and immunity must be well balanced, since any alteration in one of the parts can cause pathophysiological modifications and, can trigger changes in the immune system that can lead to autoimmunity or graft rejection [3] In this context, it is known that a successful transplant relies on a deep understanding of the immune system allied with the balance and maintenance of effector and regulatory immune mechanisms [1, 4]. The handling of costimulatory molecules, aiming the application of DC for therapeutic purposes in immune disorders such as allergies and autoimmunities, as well as in vaccination and transplantation, has received extensive attention [15] In this sense, in the attempt of modulating the activity of DC on the treatment of autoimmunity, hypersensibility, and transplant rejection, many researchers aim to develop therapies based on tolerogenic DC (tol-DC). We focus our attention on current knowledge related to immunotherapeutic advances based on the use of tolerogenic DC through inhibition of the second signal, which contribute to increasing survival of transplanted organs and tissues and reducing the use of immunosuppressive drugs
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