Delgado Mario, Gonzalez-Rey Elena, Ganea Doina
Department of Biological Sciences, Rutgers University, Newark, NJ, USA.
Ann N Y Acad Sci. 2006 Jul;1070:233-8. doi: 10.1196/annals.1317.020.
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 functional 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 CD11clowCD45RBhigh, 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 naïve 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.
耐受性树突状细胞（tDCs）通过诱导/激活调节性T细胞（Treg）在维持外周耐受性方面发挥重要作用。内源性因素有助于tDCs的功能发育。在本文中，我们提供证据表明两种已知的免疫抑制性神经肽，即血管活性肠肽（VIP）和垂体腺苷酸环化酶激活多肽（PACAP），有助于骨髓来源的tDCs的发育。VIP/PACAP产生的树突状细胞为CD11clowCD45RBhigh，在脂多糖（LPS）刺激后不上调CD80、CD86和CD40，且分泌大量白细胞介素-10。VIP/PACAP产生的树突状细胞在体外和体内均可诱导功能性Treg。VIP/树突状细胞在体内诱导抗原特异性耐受性，抑制迟发型超敏反应（DTH），并且来自接种VIP/树突状细胞小鼠的T细胞将这种抑制作用传递给未致敏宿主。VIP/PACAP对树突状细胞-Treg轴的作用代表了它们发挥一般抗炎作用的另一种机制，特别是在表现出免疫偏离或免疫特惠的解剖部位。
