Regulatory Role of ILC2 in Acute Lung Injury in Sepsis

ILC2 在脓毒症急性肺损伤中的调节作用

• 批准号: 10618774
• 负责人: Jie Fan
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10618774
• 关键词: Acute; Acute Lung Injury; Address; Affect; Automobile Driving; Bone Marrow; CASP1 gene; CXC Chemokines; Cause of Death; Cell Death; Cell surface; Cells; Cessation of life; Development; Emigrations; Endothelial Cells; Epithelial Cells; Exhibits; Foundations; G protein coupled receptor kinase; GATA3 gene; Goals; HMGB1 gene; Hematogenous; Homeostasis; Human; IL17 gene; Immune; Immune response; Individual; Infection; Inflammation; Inflammatory; Interferon Type II; Interleukin-13; Interleukin-9; Intervention; Lung; Lymphoid; Lymphoid Cell; Macrophage; Mediating; Molecular; Multiple Organ Failure; Mus; Myeloid Cells; Natural Immunity; Orphan; Pathogenesis; Pathologic; Patients; Peripheral; Persons; Physiological; Play; Population; Process; Proliferating; Pulmonary Inflammation; Research Project Grants; Retinoic Acid Receptor; Role; Sepsis; Signal Transduction; Site; Structure of parenchyma of lung; Subgroup; TSLP gene; Testing; Therapeutic Intervention; Tissue Expansion; Tissues; Virus Diseases; alveolar epithelium; chemokine receptor; cytokine; effective therapy; human disease; insight; interleukin-22; member; migration; mortality; neutrophil; novel; prevent; preventive intervention; progenitor; prophylactic; receptor; receptor for advanced glycation endproducts; recruit; sepsis induced acute lung injury; septic; septic patients; therapeutic target; therapeutically effective; transcription factor

Severe sepsis complicated with multiple organ dysfunction syndrome (MODS) is a leading cause of death in ICU. Acute lung injury (ALI) is an important component of MODS and often serves as a direct cause of death. Nonetheless, few effective therapeutic targets for ALI have been identified. Our long-term goal is to determine the mechanisms by which sepsis promote ALI, thereby potentially identifying novel targets for prophylactic intervention. Innate lymphoid cells (ILCs), a new member of the lymphoid population, play a central role in innate immunity of host response to inflammation, infection, and tissue damage. ILCs are composed of three subgroups, ILC1, ILC2, and ILC3. ILC2 are a main ILC subtype in the lungs in both human and mouse, and play an important role in maintaining airway barrier integrity and lung tissue homeostasis. However, the role of ILC2 in sepsis-induced ALI remains unclear. This research project aims to understand the regulatory role of ILC2 in the development and progression of ALI and the mechanism underlying ILC2 mobilization, migration, and expansion in the lung in sepsis through three Specific Aims (SA): SA1. To determine the role of ILC2 in the progression of ALI following sepsis; SA2 To determine the mechanism underlying ILC2 mobilization from BM and migration into the lung in sepsis; and SA3 To determine the mechanism of ILC2 expansion in the lung in sepsis. The results of the study will serve as essential foundation for potential novel treatment of ALI in sepsis by regulating ILC2 migration, expansion, and function.

严重脓毒症并发多器官功能障碍综合征（MODS）是导致死亡的主要原因 重症监护病房。急性肺损伤（ALI）是MODS的重要组成部分，通常是死亡的直接原因。 尽管如此，目前尚未确定 ALI 的有效治疗靶点。我们的长期目标是确定 脓毒症促进 ALI 的机制，从而有可能确定预防性治疗的新靶点 干涉。先天淋巴细胞 (ILC) 是淋巴群体的新成员，在 宿主对炎症、感染和组织损伤反应的先天免疫。 ILC 由三个组成 亚组：ILC1、ILC2 和 ILC3。 ILC2 是人和小鼠肺部的主要 ILC 亚型，并且 在维持气道屏障完整性和肺组织稳态中发挥重要作用。然而，角色 ILC2 在脓毒症引起的 ALI 中的作用仍不清楚。该研究项目旨在了解监管作用 ILC2 在 ALI 发生和进展中的作用以及 ILC2 动员、迁移、 通过三个特定目标 (SA) 实现脓毒症肺部扩张：SA1。确定 ILC2 在 败血症后 ALI 的进展； SA2 确定 ILC2 从 BM 动员的机制 脓毒症时迁移至肺部；和SA3 确定ILC2在肺中扩张的机制 败血症。该研究的结果将为脓毒症 ALI 的潜在新疗法奠定重要基础 通过调节 ILC2 迁移、扩展和功能。