Transcriptional control in innate lymphoid type II cells

先天淋巴细胞 II 型细胞的转录控制

基本信息

批准号：
8732115
负责人：
Dorina Avram
金额：
$ 23.7万
依托单位：
ALBANY MEDICAL COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-06-01 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8732115
关键词：
Acute Adoptive Transfer Amphiregulin Applications Grants Asthma Behavior Biology Bone Marrow Bystander Effect Cell physiology Cells Chimera organism Data Development Disease Down-Regulation Effectiveness Epidermal Growth Factor Epithelial Excision Exhibits Future Gene Expression Generations Genetic Programming Health Homeostasis Hypersensitivity Immune Immune response Immune system Immunocompetent Immunosuppressive Agents In Vitro Inflammation Inflammatory Influenza Interleukin-13 Interleukin-17 Interleukin-5 Internal Ribosome Entry Site Lung Lung Inflammation Lymphoid Lymphoid Cell Maintenance Mediating Mesentery Neutrophil Infiltration Papain Pathology Patients Peripheral Play Pneumonia Population Production Rag1 Mouse Risk Role Structure of parenchyma of lung System T-Lymphocyte Testing Therapeutic Tissues Transcription factor genes Transcriptional Regulation Type II Epithelial Receptor Cell Up-Regulation Virus Diseases airway inflammation airway remodeling cell type cytokine eosinophil in vivo interleukin-22 lymph nodes mouse model programs public health relevance research study response therapeutic target therapy development tissue repair transcription factor

项目摘要

DESCRIPTION (provided by applicant): Recent evidence shows that innate lymphoid type 2 cells (ILC2s) through production of IL-13 and IL-5 are critical in airway pathologies and tissue damage, strongly correlated with severe asthma. ILC2s not only produce IL-5 and IL-13, but also the epidermal growth factor amphiregulin, which promotes tissue remodeling and lung homeostasis following influenza infection. For developing therapeutic strategies to specifically target ILC2-mediated inflammation, while maintaining tissue repair activity, it is of crucial importance to delineate regulatory mechanisms involved in ILC2 development, maintenance and function. Our preliminary data demonstrate that Bcl11b is highly expressed in ILC2 cells in the periphery, as well as in bone marrow precursors. Induced removal of Bcl11b causes loss of their identity. Bcl11b-/- ILC2 population showed reduced IL-5 production following papain-induced lung inflammation, resulting in diminished eosinophil and increased neutrophil recruitment to the lung. Additionally, numbers of ILC2s were overall reduced in the bone marrow. In this grant application we propose to establish the role of Bcl11b in ILC2s lineage determination, in mature ILC2 cell function and identity and determine the mechanisms by which Bcl11b controls ILC2 genetic program.

描述（由申请人提供）：最近的证据表明，通过产生IL-13和IL-5，先天淋巴2型细胞（ILC2）在气道病理和组织损伤中至关重要，与严重的哮喘密切相关。 ILC2不仅产生IL-5和IL-13，还会产生表皮生长因子两极分因素，它在流感感染后促进组织重塑和肺稳态。为了制定治疗策略，以专门针对ILC2介导的炎症，同时保持组织修复活性，这对于描述参与ILC2开发，维护和功能的调节机制至关重要。我们的初步数据表明，Bcl11b在外围的ILC2细胞以及骨髓前体中高度表达。诱导的BCL11B诱导会导致其身份丧失。 Bcl11b - / - ILC2群体显示，蛋白磷灰诱导的肺部炎症后IL-5产生降低，导致嗜酸性粒细胞减少并增加肺中性粒细胞募集。另外，骨髓中总体减少了ILC2的数量。在此赠款应用中，我们建议确定Bcl11b在ILC2S谱系确定，成熟ILC2细胞功能和身份中的作用，并确定BCL11B控制ILC2遗传程序的机制。