Adorini Luciano, Penna Giuseppe, Giarratana Nadia, Roncari Andrea, Amuchastegui Susana, Daniel Kenn C, Uskokovic Milan
BioXell, Via Olgettina 58, I-20132 Milano, Italy.
J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):437-41. doi: 10.1016/j.jsbmb.2004.03.013.
Vitamin D receptor (VDR) ligands, in addition to controlling calcium metabolism, exert important effects on the growth and differentiation of many cell types and possess pronounced pro-tolerogenic immunoregulatory activities. VDR ligands can act directly on T cells, but antigen-presenting cells (APCs), and in particular dendritic cells (DCs), appear to be primary targets for their tolerogenic properties. The capacity of VDR ligands to target APCs and T cells is mediated by VDR expression in both cell types and by the presence of common targets in their signal transduction pathways, such as the nuclear factor NF-kB that is down-regulated in APCs and in T cells. VDR ligands can induce in vitro and in vivo tolerogenic DCs able to enhance CD4(+)CD25(+) suppressor T cells that, in turn, inhibit Th1 cell responses. These mechanisms of action can explain some of the immunoregulatory properties of VDR ligands, and are potentially relevant for the treatment of Th1-mediated autoimmune diseases and allograft rejection.
维生素D受体（VDR）配体除了控制钙代谢外，还对多种细胞类型的生长和分化发挥重要作用，并具有显著的促耐受性免疫调节活性。VDR配体可直接作用于T细胞，但抗原呈递细胞（APC），尤其是树突状细胞（DC），似乎是其耐受性特性的主要靶点。VDR配体靶向APC和T细胞的能力是由两种细胞类型中的VDR表达以及它们信号转导途径中共同靶点的存在介导的，例如在APC和T细胞中下调的核因子NF-κB。VDR配体可在体外和体内诱导耐受性DC，这些DC能够增强CD4(+)CD25(+)抑制性T细胞，而后者又会抑制Th1细胞反应。这些作用机制可以解释VDR配体的一些免疫调节特性，并且可能与Th1介导的自身免疫性疾病和同种异体移植排斥反应的治疗相关。
