Center of Integrated Protein Science Munich, Division of Clinical Pharmacology, LMU Munich, Germany.
Cytokine. 2012 Jul;59(1):10-7. doi: 10.1016/j.cyto.2012.03.014. Epub 2012 Apr 14.
D-dopachrome tautomerase (D-DT) is a newly described cytokine and a member of the macrophage migration inhibitory factor (MIF) protein superfamily. MIF is a broadly expressed pro-inflammatory cytokine that regulates both the innate and the adaptive immune response. MIF activates the MAP kinase cascade, modulates cell migration, and counter-acts the immunosuppressive effects of glucocorticoids. For many cell types, MIF also acts as an important survival or anti-apoptotic factor. Circulating MIF levels are elevated in the serum in different infectious and autoimmune diseases, and neutralization of the MIF protein via antibodies or small molecule antagonists improves the outcome in numerous animal models of human disease. Recently, a detailed investigation of the biological role of the closely homologous protein D-DT, which is encoded by a gene adjacent to MIF, revealed an overlapping functional spectrum with MIF. The D-DT protein also is present in most tissues and circulates in serum at similar concentrations as MIF. D-DT binds the MIF cell surface receptor complex, CD74/CD44, with high affinity and induces similar cell signaling and effector functions. Furthermore, an analysis of the signaling properties of the two proteins showed that they work cooperatively, and that neutralization of D-DT in vivo significantly decreases inflammation. In this review, we highlight the similarities and differences between MIF and D-DT, which we propose to designate "MIF-2", and discuss the implication of D-DT/MIF-2 expression for MIF-based therapies.
D-多巴色素互变异构酶（D-DT）是一种新描述的细胞因子，属于巨噬细胞移动抑制因子（MIF）蛋白超家族的成员。MIF 是一种广泛表达的促炎细胞因子，调节先天和适应性免疫反应。MIF 激活 MAP 激酶级联反应，调节细胞迁移，并对抗糖皮质激素的免疫抑制作用。对于许多细胞类型，MIF 还作为重要的存活或抗细胞凋亡因子。在不同的感染性和自身免疫性疾病中，血清中循环 MIF 水平升高，通过抗体或小分子拮抗剂中和 MIF 蛋白可改善许多人类疾病动物模型的预后。最近，对紧密同源蛋白 D-DT 的生物学作用进行了详细研究，D-DT 由 MIF 附近的基因编码，其与 MIF 具有重叠的功能谱。D-DT 蛋白也存在于大多数组织中，并以与 MIF 相似的浓度在血清中循环。D-DT 以高亲和力结合 MIF 细胞表面受体复合物 CD74/CD44，并诱导类似的细胞信号转导和效应功能。此外，对两种蛋白质的信号转导特性的分析表明，它们协同作用，体内中和 D-DT 可显著减轻炎症。在这篇综述中，我们强调了 MIF 和 D-DT 之间的相似性和差异，我们建议将其命名为“MIF-2”，并讨论了 D-DT/MIF-2 表达对基于 MIF 的治疗的影响。
