Potential Applications of Vasoactive Intestinal Peptide-Based Therapies on Transplantation

Luciana      Souza-Moreira; Virginia      Delgado-Maroto; Mario      Delgado

doi:10.2174/187153012803832567

Abstract

Vasoactive intestinal peptide (VIP) is a well-known immunoregulatory neuropeptide produced by the immune system in response to inflammation, autoimmunity or alloantigens as a natural endogenous mechanism of induction of tolerance. VIP has been proven therapeutically effective in various experimental models of autoimmune disorders and recently in human sarcoidosis. Numerous studies clearly show that VIP exerts its immunomodulatory effects by downregulating both inflammatory and Th1 responses. Recent evidences suggest that new actors enter in scene to play a role in this scenario of tolerance. By inducing antigen-specific regulatory T cells and tolerogenic dendritic cells, VIP seems to reinforce/reinstall immune tolerance, especially under autoimmune conditions. Transplantation is also a condition where VIP-related therapies emerge as promising tools for clinical application. Induction of alloantigen-specific tolerance is critical to achieve organ transplant tolerance and to avoid graft-versus-host responses following allogeneic hematopoietic transplantation. This review will focus on describing the capacity of VIP to induce suppressive/regulatory immune cells and how we can manage this cell-based therapeutic strategy to induce transplant tolerance in subjects free of immunosuppressive drugs.

Keywords: Dendritic cell, neuropeptide, regulatory T cells, tolerance, transplantation, transcriptional repressor FoxP3, cytotoxic T-lymphocyte antigen 4 (CTLA4), myeloid-derived suppressive cells (MDSCs), tolerogenic dendritic cells (tolDCs), Regulatory T cells (Treg), organ transplantation, immunointervention.