Functional Hallmarks of Healthy Macrophage Responses: Their Regulatory Basis and Disease Relevance.

Functional Hallmarks of Healthy Macrophage Responses: Their Regulatory Basis and Disease Relevance.
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DOI:
10.1146/annurev-immunol-101320-031555
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发表时间:
2022-04-26
影响因子:
29.7
通讯作者:
--
中科院分区:
医学1区
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--
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巨噬细胞是免疫系统的第一反应者。在这个角色中,它们既有中和病原体的效应子功能,也有警告其他免疫细胞不同病理威胁的哨兵功能,从而启动和协调多管齐下的免疫反应。巨噬细胞分布在全身:它们在血液中循环,排列在粘膜上,驻留在器官内,并观察结缔组织。几篇综述总结了它们在不同生理情况下以及在不同病理的启动或放大中的不同作用。在这篇综述中,我们提出健康巨噬细胞的效应子和哨兵功能依赖于三个标志性特性:反应特异性,上下文依赖性和刺激记忆。当这些标志性特性减弱时,巨噬细胞的生物功能就会受损。这反过来又导致免疫失调的风险增加,表现为免疫缺陷或自身免疫。我们回顾了支持这些标志性特性的证据和分子机制。
Macrophages are first responders for the immune system. In this role, they have both effector functions for neutralizing pathogens and sentinel functions for alerting other immune cells of diverse pathologic threats, thereby initiating and coordinating a multipronged immune response. Macrophages are distributed throughout the body: they circulate in the blood, line the mucosal membranes, reside within organs, and survey the connective tissue. Several reviews have summarized their diverse roles in different physiological scenarios and in the initiation or amplification of different pathologies. In this review, we propose that both the effector and the sentinel functions of healthy macrophages rely on three hallmark properties: Response Specificity, Context Dependence, and Stimulus Memory. When these hallmark properties are diminished, the macrophage’s biological functions are impaired. That in turn results in increased risk for immune dysregulation, manifested by immune deficiency or auto-immunity. We review the evidence and the molecular mechanisms supporting these hallmark properties.
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