CCR5 and CXCR3 are dispensable for liver infiltration, but CCR5 protects against virus-induced T-cell-mediated hepatic steatosis
CCR5 and CXCR3 are dispensable for liver infiltration, but CCR5 protects against virus-induced T-cell-mediated hepatic steatosis
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DOI：
10.1128/jvi.01242-07
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发表时间：
2007-09-01
影响因子：
5.4
通讯作者：
Thomsen, A. R.
中科院分区：
文献类型：
--
作者：
Holst, P. J.;Orskov, C.;Thomsen, A. R.
CCR 5和CXCR 3是调节活化淋巴细胞迁移的重要分子。因此，在自身免疫性病症和病毒感染的背景下发现的大多数组织浸润性T细胞表达CCR 5和CXCR 3，并且主要趋化因子配体在发炎组织内表达。因此，干预研究指出，这些受体在同种异体移植排斥、病毒感染和自身免疫模型中的非冗余作用。尽管如此，仍存在相当大的争议，许多研究未能支持CCR 5或CXCR 3在疾病发病机制中的作用。一种可能的解释是，不同的趋化因子受体可能在没有任何单个受体的情况下接管，从而使单个受体变得多余。我们试图通过分析CCR 5（-/-）、CXCR 3（-/-）和CCR 5/CXCR 3（-/-）小鼠的病毒诱导的肝脏炎症、效应细胞的产生和募集、病毒控制和免疫病理学来解决这个问题。我们的研究结果表明，CCR 5和CXCR 3主要用于组织浸润和病毒控制。相反，在CCR 5（-/-）和CCR 5/CXCR 3（-/-）小鼠中T细胞应答加速，并且CCR 5的缺乏与由显著的肝微泡性脂肪变性组成的CD 8 + T细胞介导的免疫病理学的诱导相关。
CCR5 and CXCR3 are important molecules in regulating the migration of activated lymphocytes. Thus, the majority of tissue-infiltrating T cells found in the context of autoimmune conditions and viral infections express CCR5 and CXCR3, and the principal chemokine ligands are expressed within inflamed tissues. Accordingly, intervention studies have pointed to nonredundant roles of these receptors in models of allograft rejection, viral infection, and autoinimunity. In spite of this, considerable controversy exists, with many studies failing to support a role for CCR5 or CXCR3 in disease pathogenesis. One possible explanation is that different chemokine receptors may take over in the absence of any individual receptor, thus rendering individual receptors redundant. We have attempted to address this issue by analyzing CCR5(-/-), CXCR3(-/-), and CCR5/CXCR3(-/-) mice with regard to virus-induced liver inflammation, generation and recruitment of effector cells, virus control, and immunopathology. Our results indicate that CCR5 and CXCR3 are largely dispensable for tissue infiltration and virus control. In contrast, the T-cell response is accelerated in CCR5(-/-) and CCR5/CXCR3(-/-) mice and the absence of CCR5 is associated with the induction of CD8' T-cell-mediated immunopathology consisting of marked hepatic microvesicular steatosis.