Bernasconi Pia, Cappelletti Cristina, Navone Francesca, Nessi Valeria, Baggi Fulvio, Vernos Isabelle, Romaggi Stefania, Confalonieri Paolo, Mora Marina, Morandi Lucia, Mantegazza Renato
Neurology IV, Foundation Neurological Institute Carlo Besta, Department of Medical Pharmacology, Milan, Italy.
J Neuropathol Exp Neurol. 2008 Jun;67(6):624-32. doi: 10.1097/NEN.0b013e318177e5fd.
The idiopathic inflammatory myopathies (IIMs) dermatomyositis, polymyositis, and inclusion body myositis are characterized by myofiber degeneration and inflammation. The triggering factors of muscle autoaggression in these disorders are unknown, but infiltrating T cells may be activated locally and proliferate in situ. T-cell polarization involving reorientation of cytoskeleton and microtubule-organizing centers mediated by motor proteins may occur within inflammatory cells in the muscle. We therefore analyzed ubiquitous and neuronal kinesin superfamily (KIF) members KIF-5, dynein, and KIF4 in IIM muscle biopsies and in activated peripheral blood lymphocytes from healthy donors. Only KIF-4 was altered. Transcript levels were significantly higher in IIM muscle than in controls, and KIF4 inflammatory cells were found in IIM muscles. In polymyositis and inclusion body myositis, KIF4 cells were mainly located around individual muscle fibers, whereas in dermatomyositis, they were also near blood vessels. KIF4 cells were not specific to any immune lineage, and some were Ki67. In peripheral blood lymphocytes stimulated with mitogens, interleukin 2 or anti-CD3/CD28 antibodies, KIF4 expression was upregulated, and the protein was localized in the cytoplasm in association with lysosome-associated membrane protein 1 and perforin lysosomal vesicles. These results imply that KIF4 is associated with activated T cells, irrespective of their functional phenotype, and that it is likely involved in cytoskeletal modifications associated with in situ T-cell activation in IIM.
特发性炎性肌病（IIM），包括皮肌炎、多发性肌炎和包涵体肌炎，其特征为肌纤维变性和炎症。这些疾病中肌肉自身攻击的触发因素尚不清楚，但浸润的T细胞可能在局部被激活并原位增殖。涉及由运动蛋白介导的细胞骨架和微管组织中心重新定向的T细胞极化可能发生在肌肉中的炎性细胞内。因此，我们分析了IIM肌肉活检组织以及健康供体活化外周血淋巴细胞中普遍存在的和神经元驱动蛋白超家族（KIF）成员KIF-5、动力蛋白和KIF4。只有KIF-4发生了改变。IIM肌肉中的转录水平显著高于对照组，且在IIM肌肉中发现了KIF4炎性细胞。在多发性肌炎和包涵体肌炎中，KIF4细胞主要位于单个肌纤维周围，而在皮肌炎中，它们也靠近血管。KIF4细胞并非特定于任何免疫谱系，有些是Ki67阳性。在用丝裂原、白细胞介素2或抗CD3/CD28抗体刺激的外周血淋巴细胞中，KIF4表达上调，且该蛋白定位于细胞质中，与溶酶体相关膜蛋白1和穿孔素溶酶体囊泡相关。这些结果表明，KIF4与活化的T细胞相关，无论其功能表型如何，并且它可能参与了与IIM中T细胞原位激活相关的细胞骨架修饰。
