Targeting tissue macrophage generation as a mechanism to modulate the resolution of inflammation.

组织驻留巨噬细胞是白色血细胞，分散在我们身体的组织中。它们处于宿主防御组织感染的前线，在维持组织本身的正常功能方面发挥重要作用。感染后，巨噬细胞也从血液中被募集到组织中，作为血液单核细胞到达，这些单核细胞来源于骨髓，并在到达时变成巨噬细胞。我们最近的研究强调了组织驻留和单核细胞衍生的巨噬细胞的不同起源。它们显示出基因表达的差异，这可能不仅反映了它们独特的功能编程，而且还反映了组织巨噬细胞在组织中长期生存和自我更新的机制。通过操纵巨噬细胞的特定亚群，我们的目标是使对感染和伤口修复的反应偏向，以促进有益的结果。我们提出的研究将是第一个原理验证实验，将检查一个新的研究途径，旨在控制感染和组织损伤。

Tissue resident macrophages are white blood cells that are scattered throughout and live in the tissues of our body. They are at the frontline of host defense against infection in the tissue and play important roles in maintaining the normal function of the tissue itself. After an infection, macrophages are also recruited to the tissue from the blood, arriving as blood monocytes that originate from the bone marrow and turn into macrophages upon arrival. Our recent studies highlight the quite distinct origins of tissue resident and monocyte-derived macrophages. They show differences in gene expression that probably reflect not just their distinct functional programming, but also the mechanism by which tissue macrophages are programmed to survive for long periods in the tissue, and to self-renew. By manipulating specific subsets of macrophages we aim to bias responses to infection and wound repair to promote beneficial outcomes. Our proposed studies would be first proof-of-principle experiments that would examine a new avenue of research directed at the control of infection and tissue damage.