Delgado Mario
Instituto de Parasitologia y Biomedicina, Consejo Superior de Investigaciones Cientificas, Granada 18100, Spain.
Hum Immunol. 2009 May;70(5):300-7. doi: 10.1016/j.humimm.2009.01.020.
Induction of antigen-specific tolerance is critical to prevent autoimmunity, to maintain immune homeostasis, and to achieve transplant tolerance. In addition to their classic role as sentinels of the immune response, dendritic cells (DCs) play important roles in maintaining peripheral tolerance through the induction/activation of regulatory T (Treg) cells. The possibility of generating tolerogenic DCs opens new therapeutic perspectives in autoimmune and inflammatory diseases. Characterizing endogenous factors that contribute to the development of tolerogenic DCs is highly relevant. Some neuropeptides that are produced during the ongoing inflammatory response have emerged as endogenous anti-inflammatory agents that participate in the regulation of the processes that ensure self-tolerance. Here, we examine the latest research findings indicating that the role of these neuropeptides in immune tolerance is partially mediated through differential effects on DC functions, which depend on the differentiation and activation states. Importantly, neuropeptides such as vasoactive intestinal peptide, pituitary adenylate cyclase-activating polypeptide, and melanocyte-stimulating hormone have demonstrated an ability to induce tolerogenic DCs with the capacity to generate CD4 and CD8 Treg cells. The possibility of generating or expanding ex vivo tolerogenic DCs with neuropeptides indicates the therapeutic potential for autoimmune diseases and graft-versus-host disease after allogeneic transplantation in humans.
诱导抗原特异性耐受对于预防自身免疫、维持免疫稳态以及实现移植耐受至关重要。除了作为免疫反应哨兵的经典作用外，树突状细胞（DCs）在通过诱导/激活调节性T（Treg）细胞来维持外周耐受方面也发挥着重要作用。产生耐受性DCs的可能性为自身免疫性疾病和炎症性疾病开辟了新的治疗前景。确定促成耐受性DCs发育的内源性因素具有高度相关性。一些在持续炎症反应过程中产生的神经肽已成为参与确保自身耐受过程调节的内源性抗炎剂。在此，我们研究了最新的研究结果，这些结果表明这些神经肽在免疫耐受中的作用部分是通过对DC功能的不同影响介导的，而这取决于DC的分化和激活状态。重要的是，诸如血管活性肠肽、垂体腺苷酸环化酶激活多肽和促黑素细胞激素等神经肽已证明有能力诱导产生具有生成CD4和CD8 Treg细胞能力的耐受性DCs。利用神经肽在体外产生或扩增耐受性DCs的可能性表明其在人类自身免疫性疾病和异基因移植后移植物抗宿主病中的治疗潜力。
