Centre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Nantes, France.
Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France.
Front Immunol. 2019 Sep 9;10:2131. doi: 10.3389/fimmu.2019.02131. eCollection 2019.
Corticosteroids (CS) are standard therapy for the treatment of Duchenne's muscular dystrophy (DMD). Even though they decrease inflammation, they have limited efficacy and are associated with significant side effects. There is therefore the need for new protolerogenic treatments to replace CS. Dystrophin-deficient rats ( ) closely resemble the pathological phenotype of DMD patients. We performed the first Immunophenotyping of rats and showed leukocyte infiltration in skeletal and cardiac muscles, which consisted mostly of macrophages and T cells including CD45RC T cells. Muscles of DMD patients also contain elevated CD45RC T cells. We treated rats with an anti-CD45RC MAb used in previous studies to deplete CD45RC T cells and induce immune tolerance in models of organ transplantation. Treatment of young rats with anti-CD45RC MAb corrected skeletal muscle strength and was associated with depletion of CD45RC T cells with no side effects. Treatment of young rats with prednisolone resulted in increase in skeletal muscle strength but also severe growth retardation. In conclusion, anti-CD45RC MAb treatment has potential in the treatment of DMD and might eventually result in reduction or elimination of CS use.
皮质类固醇(CS)是治疗杜氏肌营养不良症(DMD)的标准疗法。尽管它们可以减轻炎症,但疗效有限,并且存在显著的副作用。因此,需要新的耐受原性治疗方法来替代 CS。缺乏 dystrophin 的大鼠()与 DMD 患者的病理表型非常相似。我们对大鼠进行了首次免疫表型分析,显示骨骼肌和心肌中有白细胞浸润,主要由巨噬细胞和 T 细胞组成,包括 CD45RC T 细胞。DMD 患者的肌肉中也含有升高的 CD45RC T 细胞。我们用先前研究中用于耗尽 CD45RC T 细胞并在器官移植模型中诱导免疫耐受的抗 CD45RC MAb 治疗年轻的大鼠。用抗 CD45RC MAb 治疗年轻的大鼠纠正了骨骼肌力量,并且与 CD45RC T 细胞耗竭有关,没有副作用。用泼尼松龙治疗年轻的大鼠导致骨骼肌力量增加,但也严重生长迟缓。总之,抗 CD45RC MAb 治疗具有治疗 DMD 的潜力,最终可能会减少或消除 CS 的使用。