Rheumatology Group, Centre for Inflammatory Diseases, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia.
Centre for Molecular Innovation, The Feinstein Institute for Medical Research, Manhasset, NY, USA.
Trends Immunol. 2019 May;40(5):447-462. doi: 10.1016/j.it.2019.03.002. Epub 2019 Apr 5.
Produced by many cell types, macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine with critical and supporting roles in many disease states and conditions. Its disease associations, myriad functions, receptors, and downstream signaling have been the subject of considerable research, yet many questions remain. Moreover, the relevance of MIF's partially functionally redundant family member, D-dopachrome tautomerase (D-DT), also remains to be further characterized. Here, we discuss recent discoveries demonstrating direct roles of MIF in supporting NLR Family Pyrin Domain-Containing 3 (NRLP3) inflammasome activation, as well as acting as a molecular chaperone for intracellular proteins. These findings may offer new clues to understanding MIF's multiple functions, and assist the development of putative MIF-targeting therapeutics for a variety of pathologies.
由多种细胞类型产生的巨噬细胞移动抑制因子（MIF）是一种多效细胞因子，在许多疾病状态和情况下具有关键和支持作用。其与疾病的关联、众多功能、受体和下游信号转导一直是相当多研究的主题，但仍有许多问题存在。此外，MIF 的部分功能冗余家族成员 D-多巴色素互变异构酶（D-DT）的相关性也有待进一步阐明。在这里，我们讨论了最近的发现，这些发现表明 MIF 在支持 NOD、LRR 和富含亮氨酸重复蛋白 3（NLRP3）炎性体激活以及作为细胞内蛋白的分子伴侣方面发挥直接作用。这些发现可能为理解 MIF 的多种功能提供新的线索，并有助于开发针对多种病理的潜在 MIF 靶向治疗药物。
