Educating Macrophages in vivo

巨噬细胞是白色血细胞，可以以许多不同的激活状态存在，其中一些驱动组织损伤，其中一些促进修复。因此，体内存在的巨噬细胞亚群的平衡对于控制长期的破坏性反应至关重要，因此，获得正确的平衡可以预防疾病。我们对巨噬细胞的理解在过去十年中有所增长，现在认识到巨噬细胞存在于不同的激活状态，具有不同的功能：所谓的“M1”细胞驱动组织损伤，而“M2”细胞被认为参与愈合。然而，我们对M1和M2的大部分理解和定义都来自于体外细胞培养，目前还不知道这些想法如何转化为复杂的体内组织环境。因此，在体内，巨噬细胞可以从组织接收多种激活信号，并且可以通过不同的激活状态转变。由于组织损伤的结果取决于M2-样细胞和M1-样细胞的平衡，有利于M2，很明显，定义体内驱动信号是至关重要的。因此，仍然存在未满足的需要，以丰富我们对体内组织巨噬细胞的生物学的理解。我们已经建立了一个肠道炎症的小鼠模型，作为一个强大的系统来定义肠道巨噬细胞群，并表明巨噬细胞的亚群，首先是M1，其次是M2样巨噬细胞，以一种可预测的方式出现。使用我们的模型，我们询问在复杂的组织环境中，在体内去除特定的细胞信号是否会阻止M2样细胞的出现。此外，我们在组织修复，保护免受损伤和保护免受感染的背景下解决组织巨噬细胞的功能。我们的中心假设是，在组织损伤期间存在的巨噬细胞类型的平衡决定了组织修复的潜力。这对健康和改善疾病结果很重要，因为防止组织长时间暴露于炎症很重要。

Macrophages are white blood cells which can exist in many different activation states, some of which drive tissue damage and some of which promote repair. The balance of macrophage subpopulations that exists in vivo is therefore central to controlling long term damaging responses and, as such, getting the balance right can prevent disease. Our understanding of the macrophage has grown over the last decade and it is now recognised that macrophages exist in different activation states which have different functions: the so called "M1" cell drives tissue damage whilst "M2" cells are thought to be involved in healing. Much of our understanding, and the definition of M1 and M2, however, derives from refined in vitro cell cultures and it is not known how well these ideas translate to a complex in vivo tissue environment. Thus, in vivo the macrophage may receive multiple activation signals from the tissue and may transit through different activation states. As the outcome of damage to tissues depends on the balance of M2-like cells and M1-like cells in favour of M2 it is clear that defining the driving signals in vivo is paramount. There thus remains an unmet need to enrich our understanding of the biology of the tissue macrophage in vivo. Armed with the knowledge of what important signals are, which support the M2-like cell in vivo, we can then begin developing therapies to prevent disease by enriching for this macrophage subpopulation.We have established a mouse model of gut inflammation as a robust system for defining intestinal macrophage populations and have shown that subpopulations of macrophages, firstly M1, followed by M2-like macrophages, emerge in a robust and predictable fashion. Using our model we ask whether removing specific cell signals in vivo, in the context of a complex tissue environment, prevents the emergence of the M2-like cell. In addition we address function of the tissue macrophages in the context of tissue repair, protection from damage and protection from infection.Our central hypothesis is that the balance of macrophage cell types that exist during tissue damage determines the potential for the tissue to repair. This is important for health and improved disease outcomes as it is important to prevent tissues being exposed to inflammation for prolonged periods of time.