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

组织常驻巨噬细胞是分散在我们身体组织中的白细胞。它们在组织中处于宿主防御感染的第一线，对维持组织自身的正常功能起着重要作用。感染后，巨噬细胞也从血液中被招募到组织中，作为血液单核细胞到达，这些单核细胞起源于骨髓，到达后变成巨噬细胞。我们最近的研究强调了组织常驻和单核细胞来源的巨噬细胞的完全不同的起源。它们表现出的基因表达差异可能不仅反映了它们不同的功能程序，也反映了组织巨噬细胞在组织中长时间存活和自我更新的机制。通过操纵巨噬细胞的特定亚群，我们的目标是对感染和伤口修复产生偏倚反应，以促进有益的结果。我们提出的研究将是第一个原理证明实验，将检验一个新的研究途径，指导感染和组织损伤的控制。

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.