Macrophage-mediated regulation of inflammation and tissue repair

巨噬细胞介导的炎症和组织修复调节

• 批准号: 10714025
• 负责人: Ruth A Franklin
• 金额: $ 42.38万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10714025
• 关键词: Biological; Cell Communication; Cell physiology; Cells; Chemicals; Communication; Complex; Development; Disease; Environment; Epithelial Cells; Epithelium; Goals; Homeostasis; Immune; Immunologic Surveillance; Infection; Inflammation; Inflammatory; Inflammatory Response; Injury; Knowledge; Laboratories; Macrophage; Mediating; Modeling; Mucous Membrane; Natural Immunity; Organoids; Pathologic; Play; Population; Regenerative Medicine; Regulation; Research; Role; Site; Source; System; Tissues; Viral; Work; cell type; epithelial repair; epithelium regeneration; in vivo; insight; interdisciplinary approach; interest; novel; novel therapeutic intervention; pathogen; progenitor; programs; repaired; reparative capacity; response; stem; tissue repair

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.

项目摘要 炎症是病原体清除和组织修复所必需的。粘液组织连续 与外部环境接触，使这些部位极易受到感染和组织损伤， 各种来源。损伤可能是由于外部损伤和随后的炎症反应而发生的。 级联。因此，需要强有力的反应来抑制炎症和修复受损组织。 已知上皮修复通过局部干细胞和祖细胞群体发生，然而， 局部微环境中的上皮细胞和免疫细胞更加神秘。一种这样的细胞类型， 巨噬细胞在多种组织的免疫监视、修复和体内平衡中起重要作用。 然而，巨噬细胞在上皮再生中的直接作用还不清楚。在我的实验室里 在接下来的几年里，我们将探讨巨噬细胞在调节炎症反应中的作用， 促进组织修复和重塑。更具体地说，我们对破译巨噬细胞- 粘膜组织中病毒和化学损伤后的上皮细胞相互作用， 修复.我们将使用体内损伤模型和离体类器官系统来：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。我们提出的跨学科方法在接口 先天免疫和再生医学之间的联系将为生物学问题带来新的见解 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，增强修复 在感染和损伤后，并减少与许多疾病相关的病理组织重塑 states.