Macrophage-mediated regulation of inflammation and tissue repair

项目总结 炎症是病原体清除和组织修复所必需的。粘膜组织是连续的 与外部环境接触，使这些部位极易受到感染和组织损伤 各种各样的消息来源。损害可能是外部侮辱和随之而来的炎症的结果 卡斯卡德。因此，既要抑制炎症，又要修复受损的组织，就需要强有力的反应。 已知上皮修复是通过局部干细胞和祖细胞群体发生的，然而， 局部微环境内的上皮细胞和免疫细胞较为神秘。一种这样的细胞类型，即 巨噬细胞在多种组织的免疫监视、修复和动态平衡中发挥重要作用。 然而，巨噬细胞在上皮再生中的直接作用还不是很清楚。在我的实验室里 在接下来的几年里，我们将询问巨噬细胞在调节炎症反应和 促进组织修复和重塑。更具体地说，我们感兴趣的是破译巨噬细胞- 粘膜组织中病毒和化学损伤后的上皮细胞相互作用以确定新的调控因子 修理。我们将使用体内损伤模型和体外有机系统来：1)确定巨噬细胞如何 调节炎症反应以促进宿主存活和2)确定巨噬细胞如何介导组织修复 通过与上皮细胞的交流。 我的研究计划的长期目标是扩大我们对免疫细胞功能的了解 屏障组织中的组织修复和重塑。我们在界面上提出的跨学科方法 先天免疫和再生医学之间的关系将为中心的生物问题带来新的见解 许多复杂的疾病。了解免疫细胞群体的修复能力将使 开发新的治疗策略以抑制病理性炎症反应，促进修复 在感染和损伤后，并减少与许多疾病相关的病理组织重塑 各州。

PROJECT SUMMARY Inflammation is required for both pathogen clearance and tissue repair. Mucosal tissues are in continuous contact with the external environment, making these sites highly vulnerable to infection and tissue damage from a variety of sources. Damage can occur as a result of both external insults and the ensuing inflammatory cascade. Therefore, robust responses are required to both dampen inflammation and repair damaged tissue. Epithelial repair is known to occur through local stem and progenitor populations, however, the interplay between the epithelium and immune cells within the local microenvironment is more enigmatic. One such cell type, the macrophage, plays important roles in immune surveillance, repair, and homeostasis across multiple tissues. However, the direct role of macrophages in epithelial regeneration is not well understood. In my laboratory over the next several years, we will interrogate the role of macrophages in regulating inflammatory responses and promoting tissue repair and remodeling. More specifically, we are interested in deciphering macrophage- epithelial cell interactions following viral and chemical damage in mucosal tissues to identify novel regulators of repair. We will use both in vivo damage models and ex vivo organoid systems to: 1) determine how macrophages regulate inflammatory responses to promote host survival and 2) define how macrophages mediate tissue repair through communication with epithelial cells. The long-term goal of my research program is to expand our knowledge surrounding immune cell functions in tissue repair and remodeling in barrier tissues. Our proposed interdisciplinary approaches at the interface between innate immunity and regenerative medicine will bring fresh insight to biological problems at the center of many complex diseases. Understanding the reparative capacity of immune cell populations will allow development of new therapeutic strategies to dampen pathological inflammatory responses, enhance repair following infection and injury, and decrease the pathological tissue remodeling associated with many disease states.