Transcriptional control in innate lymphoid type II cells

先天淋巴细胞 II 型细胞的转录控制

• 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
• 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

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的先天淋巴2型细胞（ILC 2）在气道病理和组织损伤中至关重要，与重度哮喘密切相关。ILC 2不仅产生IL-5和IL-13，而且还产生表皮生长因子双调蛋白，其促进流感感染后的组织重塑和肺内稳态。为了开发特异性靶向ILC 2介导的炎症的治疗策略，同时维持组织修复活性，描述参与ILC 2发育、维持和功能的调控机制至关重要。我们的初步数据表明，Bcl 11b是高度表达的ILC 2细胞在周边，以及在骨髓前体。诱导Bcl 11b的去除导致其身份的丧失。Bcl 11b-/-ILC 2群体在木瓜蛋白酶诱导的肺部炎症后显示IL-5产生减少，导致嗜酸性粒细胞减少和中性粒细胞向肺的募集增加。此外，骨髓中ILC 2的数量总体上减少。在本申请中，我们建议确定Bcl 11b在ILC 2谱系确定、成熟ILC 2细胞功能和身份中的作用，并确定Bcl 11b控制ILC 2遗传程序的机制。