Macrophage migration inhibitory factor (MIF) is a protein that acts as a cytokine-, enzyme-, endocrine- and chaperon-like molecule. It binds to the cell-surface receptor CD74 in association with CD44, which activates the downstream signal transduction pathway. In addition, MIF acts also as a noncognate ligand for C-X-C chemokine receptor type 2 (CXCR2), type 4 (CXCR4), and type 7 (CXCR7). Recently, D-dopachrome tautomerase (D-DT), a second member of the MIF superfamily, was identified. From a pharmacological and clinical point of view, the nonredundant biological properties of MIF and D-DT anticipate potential synergisms from their simultaneous inhibition. Here, we focus on the role of MIF and D-DT in human immune-inflammatory, autoimmune, and chronic respiratory diseases, providing an update on the progress made in the identification of specific small-molecule inhibitors of these proteins.

巨噬细胞迁移抑制因子（MIF）是一种蛋白质，可作为细胞因子，酶，内分泌和分子伴侣样分子。它与CD44结合到细胞表面受体CD74上，从而激活下游信号转导途径。此外，MIF还充当CXC趋化因子受体2型（CXCR2），4型（CXCR4）和7型（CXCR7）的非同源配体。最近，发现了MIF超家族的第二个成员D-dopachrome互变异构酶（D-DT）。从药理学和临床的角度来看，MIF和D-DT的非冗余生物学特性可从其同时抑制中预见潜在的协同作用。在这里，我们重点介绍MIF和D-DT在人类免疫炎症，自身免疫和慢性呼吸系统疾病中的作用，