Macrophage heterogeneity in liver injury and fibrosis
Macrophage heterogeneity in liver injury and fibrosis
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DOI：
10.1016/j.jhep.2013.12.025
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发表时间：
2014-05-01
影响因子：
25.7
通讯作者：
Zimmermann, Henning W.
中科院分区：
文献类型：
--
作者：
Tacke, Frank;Zimmermann, Henning W.
肝巨噬细胞在慢性肝损伤的发病机制中起着核心作用，并被认为是对抗纤维化的潜在靶点。最近的动物模型实验研究表明，肝巨噬细胞是一种非常异质的免疫细胞群，在体内平衡、疾病进展和损伤恢复中发挥着不同的功能。这些包括清除病原体或细胞碎片和维持稳态条件下的免疫耐受；在启动和延续炎症反应损伤的核心作用；慢性肝损伤通过激活肝星状细胞促进肝纤维化最后，通过细胞外基质的降解和抗炎细胞因子的释放来解决炎症和纤维化。肝脏的细胞异质性部分可以用巨噬细胞的起源来解释。肝巨噬细胞可以来自循环单核细胞，通过趋化因子信号被募集到损伤的肝脏，也可以来自自我更新的胚胎来源的局部巨噬细胞，称为Kupffer细胞。库普弗细胞对于感知组织损伤和启动炎症反应至关重要，而浸润的Ly-6C（+）单核细胞来源的巨噬细胞与慢性炎症和纤维形成有关。此外，局部或募集的巨噬细胞的增殖可能进一步促进它们在受损肝脏中的积累。在纤维化消退过程中，单核细胞来源的细胞分化为低表达的Ly-6C （Ly6C, Gr1）的“恢复性”巨噬细胞，促进损伤的消退。了解调节肝巨噬细胞异质性的机制，无论是通过单核细胞亚群募集，通过促进巨噬细胞的恢复性极化，还是通过影响巨噬细胞独特的效应功能，都可能有助于开发新的巨噬细胞亚群靶向治疗肝损伤和纤维化的方法。2014年欧洲肝脏研究协会。Elsevier b.v.版权所有。
Hepatic macrophages are central in the pathogenesis of chronic liver injury and have been proposed as potential targets in combatting fibrosis. Recent experimental studies in animal models revealed that hepatic macrophages are a remarkably heterogeneous population of immune cells that fulfill diverse functions in homeostasis, disease progression, and regression from injury. These range from clearance of pathogens or cellular debris and maintenance of immunological tolerance in steady state conditions; central roles in initiating and perpetuating inflammation in response to injury; promoting liver fibrosis via activating hepatic stellate cells in chronic liver damage; and, finally, resolution of inflammation and fibrosis by degradation of extracellular matrix and release of anti-inflammatory cytokines. Cellular heterogeneity in the liver is partly explained by the origin of macrophages. Hepatic macrophages can either arise from circulating monocytes, which are recruited to the injured liver via chemokine signals, or from self-renewing embryo-derived local macrophages, termed Kupffer cells. Kupffer cells appear essential for sensing tissue injury and initiating inflammatory responses, while infiltrating Ly-6C(+) monocyte-derived macrophages are linked to chronic inflammation and fibrogenesis. In addition, proliferation of local or recruited macrophages may possibly further contribute to their accumulation in injured liver. During fibrosis regression, monocyte-derived cells differentiate into Ly-6C (Ly6C, Gr1) low expressing ` restorative' macrophages and promote resolution from injury. Understanding the mechanisms that regulate hepatic macrophage heterogeneity, either by monocyte subset recruitment, by promoting restorative macrophage polarization or by impacting distinctive macrophage effector functions, may help to develop novel macrophage subset-targeted therapies for liver injury and fibrosis. (c) 2014 European Association for the Study of the Liver. Published by Elsevier B. V. All rights reserved.