Larrubia Juan R, Benito-Martínez Selma, Calvino Miryam, Sanz-de-Villalobos Eduardo, Parra-Cid Trinidad
World J Gastroenterol. 2008 Dec 21;14(47):7149-59. doi: 10.3748/wjg.14.7149.
Chemokines produced in the liver during hepatitis C virus (HCV) infection induce migration of activated T cells from the periphery to infected parenchyma. The milieu of chemokines secreted by infected hepatocytes is predominantly associated with the T-helper cell/Tc1 T cell (Th1/Tc1) response. These chemokines consist of CCL3 (macrophage inflammatory protein-1 alpha; MIP-1 alpha), CCL4 (MIP-1 beta), CCL5 (regulated on activation normal T cell expressed and secreted; RANTES), CXCL10 (interferon-gamma-inducible protein-10; IP-10), CXCL11 (interferon-inducible T-cell alpha chemoattractant; I-TAC), and CXCL9 (monokine induced by interferon gamma; Mig) and they recruit T cells expressing either CCR5 or CXCR3 chemokine receptors. Intrahepatic and peripheral blood levels of these chemokines are increased during chronic hepatitis C. The interaction between chemokines and their receptors is essential in recruiting HCV-specific T cells to control the infection. When the adaptive immune response fails in this task, non-specific T cells without the capacity to control the infection are also recruited to the liver, and these are ultimately responsible for the persistent hepatic damage. The modulation of chemokine receptor expression and chemokine secretion could be a viral escape mechanism to avoid specific T cell migration to the liver during the early phase of infection, and to maintain liver viability during the chronic phase, by impairing non-specific T cell migration. Some chemokines and their receptors correlate with liver damage, and CXCL10 (IP-10) and CXCR3 levels have shown a clinical utility as predictors of treatment response outcome. The regulation of chemokines and their receptors could be a future potential therapeutic target to decrease liver inflammation and to increase specific T cell migration to the infected liver.
丙型肝炎病毒（HCV）感染期间肝脏产生的趋化因子可诱导活化的T细胞从外周迁移至被感染的实质组织。被感染肝细胞分泌的趋化因子环境主要与辅助性T细胞/Tc1 T细胞（Th1/Tc1）应答相关。这些趋化因子包括CCL3（巨噬细胞炎性蛋白-1α；MIP-1α）、CCL4（MIP-1β）、CCL5（活化正常T细胞表达和分泌调控因子；RANTES）、CXCL10（γ干扰素诱导蛋白-10；IP-10）、CXCL11（干扰素诱导T细胞α趋化因子；I-TAC）以及CXCL9（γ干扰素诱导的单核因子；Mig），它们可募集表达CCR5或CXCR3趋化因子受体的T细胞。在慢性丙型肝炎期间，这些趋化因子的肝内和外周血水平会升高。趋化因子与其受体之间的相互作用对于募集HCV特异性T细胞以控制感染至关重要。当适应性免疫应答无法完成此任务时，无控制感染能力的非特异性T细胞也会被募集至肝脏，而这些细胞最终会导致持续性肝损伤。趋化因子受体表达和趋化因子分泌的调节可能是一种病毒逃逸机制，通过损害非特异性T细胞迁移，在感染早期避免特异性T细胞迁移至肝脏，并在慢性期维持肝脏活力。一些趋化因子及其受体与肝损伤相关，CXCL10（IP-10）和CXCR3水平已显示出作为治疗反应结果预测指标的临床实用性。趋化因子及其受体的调节可能是未来潜在的治疗靶点，以减轻肝脏炎症并增加特异性T细胞向被感染肝脏的迁移。
