Rubio Serina, Somers Veerle, Fraussen Judith
Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, Hasselt, 3500, Belgium.
Eur J Immunol. 2024 Dec;54(12):e2451333. doi: 10.1002/eji.202451333. Epub 2024 Nov 3.
Traumatic spinal cord injury (SCI) is a severe condition leading to long-term impairment of motor, sensory, and autonomic functions. Following the initial injury, a series of additional events is initiated further damaging the spinal cord. During this secondary injury phase, both an inflammatory and immune modulatory response are triggered that have damaging and anti-inflammatory properties, respectively. The proinflammatory cytokine macrophage migration inhibitory factor (MIF) and its receptor CD74 have been extensively studied in traumatic SCI. MIF expression is increased in spinal cord tissue after experimental SCI, mainly in astrocytes and microglia, as well as in the plasma of SCI patients. Functionally, MIF and CD74 were shown to regulate astrocyte viability, proliferation and cholesterol metabolism, microglia migration, and neuronal viability. Moreover, inhibition of the MIF/CD74 axis improved the functional recovery of SCI animals. We provide a detailed overview of studies analyzing the role of MIF and CD74 in traumatic SCI. We describe results from animal studies, using rat and mouse models for SCI, and human studies. Furthermore, we propose a new path for investigation, focused on B cells, that might lead to a better understanding of how MIF and CD74 contribute to the secondary injury cascade following traumatic SCI.
创伤性脊髓损伤（SCI）是一种严重疾病，会导致运动、感觉和自主神经功能的长期损害。在初始损伤后，会引发一系列额外事件，进一步损害脊髓。在这个继发性损伤阶段，会分别触发具有损伤性和抗炎性的炎症和免疫调节反应。促炎细胞因子巨噬细胞移动抑制因子（MIF）及其受体CD74在创伤性SCI中已得到广泛研究。实验性SCI后，脊髓组织中MIF表达增加，主要存在于星形胶质细胞和小胶质细胞中，在SCI患者的血浆中也有增加。在功能上，MIF和CD74被证明可调节星形胶质细胞的活力、增殖和胆固醇代谢、小胶质细胞迁移以及神经元活力。此外，抑制MIF/CD74轴可改善SCI动物的功能恢复。我们详细概述了分析MIF和CD74在创伤性SCI中作用的研究。我们描述了使用大鼠和小鼠SCI模型的动物研究以及人体研究的结果。此外，我们提出了一条以B细胞为重点的新研究途径，这可能有助于更好地理解MIF和CD74如何在创伤性SCI后的继发性损伤级联反应中发挥作用。
