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）是严重急性呼吸衰竭患者的主要死亡原因， 重症监护室急性肺损伤（acute lung injury，ALI）是多器官功能不全综合征（MODS）的一个重要组成部分，也是导致患者死亡的直接原因。 然而，很少有有效的治疗ALI的目标已经确定。我们的长期目标是确定 脓毒症促进ALI的机制，从而潜在地确定预防ALI的新靶点。 干预先天性淋巴样细胞（inate lymphoid cells，ILC）是淋巴样细胞群中的一个新成员，在免疫调节中起着重要作用。 宿主对炎症、感染和组织损伤的先天免疫反应。ILC由三个组成 亚组，ILC 1，ILC 2和ILC 3。ILC 2是人和小鼠肺中的主要ILC亚型，并且 在维持气道屏障完整性和肺组织稳态中起重要作用。然而， ILC 2在脓毒症诱导的ALI中的作用尚不清楚。本研究项目旨在了解 ILC 2在ALI的发生和发展中的作用以及ILC 2动员、迁移、 以及通过三个特异性目的（SA）在脓毒症中在肺中的扩张：SA 1.确定国际法委员会第二届会议在 脓毒症后ALI的进展; SA 2确定ILC 2从BM动员的潜在机制 为了确定ILC 2在脓毒症中肺中扩增的机制， 败血症本研究的结果将为脓毒症急性肺损伤的潜在治疗提供重要的基础 通过调节ILC 2的迁移、扩展和功能。