Educating Macrophages in vivo

巨噬细胞是一种白细胞，可以以多种不同的激活状态存在，其中一些会导致组织损伤，一些会促进修复。因此，体内存在的巨噬细胞亚群的平衡是控制长期破坏性反应的核心，因此，正确的平衡可以预防疾病。在过去的十年里，我们对巨噬细胞的了解不断增长，现在人们认识到，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”细胞被认为参与修复。然而，我们的大部分理解以及M1和M2的定义都来自于精炼的体外细胞培养，目前尚不清楚这些想法如何很好地转化为复杂的活体组织环境。因此，在体内，巨噬细胞可以接收来自组织的多种激活信号，并可能通过不同的激活状态。由于组织损伤的结果取决于M2样细胞和M1样细胞有利于M2的平衡，很明显，在体内确定驱动信号是至关重要的。因此，丰富我们对体内组织巨噬细胞生物学的理解仍然是一个未得到满足的需求。有了支持体内M2样细胞的重要信号的知识，我们就可以开始开发通过丰富这种巨噬细胞亚群来预防疾病的治疗方法。我们已经建立了一个小鼠肠道炎症模型，作为定义肠道巨噬细胞种群的强大系统，并表明巨噬细胞亚群，首先是M1，然后是M2样巨噬细胞，以一种强大和可预测的方式出现。使用我们的模型，我们问，在复杂的组织环境中，在体内移除特定的细胞信号是否可以防止M2样细胞的出现。此外，我们还讨论了组织巨噬细胞在组织修复、防止损伤和防止感染方面的功能。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在炎症中是重要的。

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.