Raju Raghavanpillai, Vasconcelos Olavo, Granger Rebekah, Dalakas Marinos C
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1382, USA.
J Neuroimmunol. 2003 Aug;141(1-2):125-31. doi: 10.1016/s0165-5728(03)00218-2.
Because IFN-gamma-inducible chemokines, Mig (CXCL9), IP-10 (CXCL10), I-TAC (CXCL11) and their receptor, CXCR3, are critical molecules in T cell trafficking and generation of effector T cells, we examined their expression in the muscle biopsies of patients with sporadic inclusion body myositis (s-IBM) and disease controls. The functional role of these molecules was also studied by examining the effect and time kinetics of IFN-gamma in inducing Mig and IP-10 expression in human myotubes in vitro. We found significantly high levels of Mig and IP-10 mRNA expression in s-IBM muscles compared to controls. IFN-gamma upregulated the mRNA expression of Mig and IP-10 by human myotubes in a dose-dependent manner. By double-label immunohistochemistry, Mig was expressed on a subset of CD8(+) cells and the areas of the muscle fiber in contact or contiguous to the T cells; CXCR3 was expressed only on a subset of the autoinvasive CD8(+) T cells but not the myofibers. IP-10 and I-TAC were not detected by immunocytochemistry. The findings indicate that in s-IBM, IFN-gamma is involved in the upregulation and in situ production of proinflammatory chemokines, which, in turn, participate in the recruitment of activated T cells and contribute to the self-sustaining nature of endomysial inflammation.
由于γ干扰素诱导的趋化因子Mig（CXCL9）、IP-10（CXCL10）、I-TAC（CXCL11）及其受体CXCR3是T细胞迁移和效应T细胞生成中的关键分子，我们检测了散发性包涵体肌炎（s-IBM）患者和疾病对照者肌肉活检组织中它们的表达情况。还通过检测γ干扰素在体外诱导人肌管中Mig和IP-10表达的作用及时间动力学，研究了这些分子的功能作用。我们发现，与对照组相比，s-IBM肌肉中Mig和IP-10 mRNA表达水平显著升高。γ干扰素以剂量依赖的方式上调人肌管中Mig和IP-10的mRNA表达。通过双重免疫组织化学法，Mig在一部分CD8(+)细胞以及与T细胞接触或相邻的肌纤维区域表达；CXCR3仅在一部分自身侵袭性CD8(+) T细胞上表达，而不在肌纤维上表达。免疫细胞化学未检测到IP-10和I-TAC。这些发现表明，在s-IBM中，γ干扰素参与促炎趋化因子的上调和原位产生，进而参与活化T细胞的募集，并促成肌内膜炎症的自我维持特性。
