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: 10293529
• 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/10293529
• 关键词: Acute; Acute Lung Injury; Address; Affect; Attenuated; 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 Protein; Hematogenous; Homeostasis; Human; Immune; Immune response; Individual; Infection; Inflammation; Inflammatory; Interferon Type II; Interferons; Interleukin-13; Interleukin-17; Interleukin-9; Intervention; Lung; Lymphoid; Lymphoid Cell; Mediating; Molecular; Multiple Organ Failure; Mus; Myeloid Cells; Natural Immunity; Orphan; Pathogenesis; Pathologic; Patients; Peripheral; Persons; Physiological; Play; Population; Process; 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; alveolar epithelium; base; chemokine receptor; cytokine; effective therapy; human disease; insight; interleukin-22; macrophage; 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.

严重的败血症与多个器官功能障碍综合征（MOD）复杂化是死亡的主要原因 ICU。急性肺损伤（ALI）是MOD的重要组成部分，通常是直接死亡原因。 但是，几乎没有发现ALI的有效治疗靶标。我们的长期目标是确定 败血症促进ALI的机制，从而有可能识别预防性的新靶 干涉。先天淋巴样细胞（ILC）是淋巴样种群的新成员，在 对宿主对炎症，感染和组织损伤的反应的先天免疫力。 ILC由三个 亚组，ILC1，ILC2和ILC3。 ILC2是人和小鼠的肺中的主要ILC亚型， 在维持气道屏障完整性和肺组织稳态方面发挥重要作用。但是， 败血症引起的ALI中的ILC2尚不清楚。该研究项目旨在了解 ILC2在ALI的发展和发展中以及ILC2动员，迁移， 并通过三个特定目标（SA）：SA1在败血症中的肺部扩张。确定ILC2在 败血症后阿里的进展； SA2确定BM的ILC2动员基础机制 并在败血症中迁移到肺部；和SA3确定肺中ILC2膨胀的机理 败血症。该研究的结果将成为败血症中潜在新型ALI治疗的基础 通过调节ILC2迁移，扩展和功能。