Vasoactive Intestinal Peptide:The Dendritic Cell → Regulatory T Cell Axis

摘要

Tolerogenic dendritic cells (tDCs) play an important role in maintaining peripheral tolerance through the induction/activation of regulatory T cells (Treg). Endogenous factors contribute to the func-tional development of tDCs. In this article, we present evidence that two known immunosuppressive neuropeptides, the vasoactive intestinal peptide (VIP) and the pituitary adenylate cyclase-activating polypeptide (PACAP), contribute to the development of bone marrow-derived tDCs. The VIP/PACAP-generated DCs are CD11c~(low) CD45RB~(high), do not upregulate CD80, CD86, and CD40 following lipopolysaccharide (LPS) stimulation, and secrete high amounts of IL-10. The VIP/PACAP-generated DCs induce functional Treg in vitro and in vivo. VIP/DCs induce antigen-specific tolerance in vivo, suppress delayed-type hypersensitivity (DTH), and T cells from VIP/DC-inoculated mice transfer the suppression to naive hosts. The effect of VIP/PACAP on the DC-Treg axis represents an additional mechanism for their general anti-inflammatory role, particularly in anatomical sites that exhibit immune deviation or privilege.