Cancer Inflammation Program, National Cancer Institute at Frederick, NIH, Frederick, MD, USA.
Immunology. 2015 Apr;144(4):541-8. doi: 10.1111/imm.12451.
Macrophages have been at the heart of immune research for over a century and are an integral component of innate immunity. Macrophages are often viewed as terminally differentiated monocytic phagocytes. They infiltrate tissues during inflammation, and form polarized populations that perform pro-inflammatory or anti-inflammatory functions. Tissue-resident macrophages were regarded as differentiated monocytes, which seed the tissues to perform immune sentinel and homeostatic functions. However, tissue-resident macrophages are not a homogeneous population, but are in fact a grouping of cells with similar functions and phenotypes. In the last decade, it has been revealed that many of these cells are not terminally differentiated and, in most cases, are not derived from haematopoiesis in the adult. Recent research has highlighted that tissue-resident macrophages cannot be grouped into simple polarized categories, especially in vivo, when they are exposed to complex signalling events. It has now been demonstrated that the tissue environment itself is a major controller of macrophage phenotype, and can influence the expression of many genes regardless of origin. This is consistent with the concept that cells within different tissues have diverse responses in inflammation. There is still a mountain to climb in the field, as it evolves to encompass not only tissue-resident macrophage diversity, but also categorization of specific tissue environments and the plasticity of macrophages themselves. This knowledge provides a new perspective on therapeutic strategies, as macrophage subsets can potentially be manipulated to control the inflammatory environment in a tissue-specific manner.
巨噬细胞在一个多世纪以来一直是免疫研究的核心，是先天免疫的一个组成部分。巨噬细胞通常被视为终末分化的单核吞噬细胞。它们在炎症期间浸润组织，并形成极化群体，发挥促炎或抗炎功能。组织驻留巨噬细胞被认为是分化的单核细胞，它们在组织中播散，以发挥免疫监视和维持内稳态的功能。然而，组织驻留巨噬细胞不是一个同质群体，而是实际上是具有相似功能和表型的细胞群体。在过去的十年中，已经揭示出许多这些细胞没有终末分化，并且在大多数情况下，它们不是来自成人造血。最近的研究强调，组织驻留巨噬细胞不能简单地分为极化类别，尤其是在体内，当它们暴露于复杂的信号事件时。现在已经证明，组织环境本身是巨噬细胞表型的主要控制器，并且可以影响许多基因的表达，而与起源无关。这与不同组织内的细胞在炎症中有不同反应的概念是一致的。在该领域还有很多工作要做，因为它不仅需要涵盖组织驻留巨噬细胞的多样性，还需要对特定组织环境进行分类以及巨噬细胞本身的可塑性。这一知识为治疗策略提供了新的视角，因为巨噬细胞亚群可以潜在地被操纵，以组织特异性的方式控制炎症环境。
