Unique Aspects of Respiratory Immunity

呼吸免疫的独特之处

• 批准号: 8669035
• 负责人: Troy D Randall
• 金额: $ 37.85万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8669035
• 关键词: Allergic Disease; Anti-Inflammatory Agents; Anti-inflammatory; Antigens; Area; Asthma; B-Lymphocytes; Bronchus-Associated Lymphoid Tissue; CCL19 gene; CCL21 gene; CXCL13 gene; Cells; Characteristics; Chronic; Chronic Obstructive Airway Disease; Chronic lung disease; Coin; Data; Development; Disease; Exposure to; Extrinsic allergic alveolitis; Helper-Inducer T-Lymphocyte; Home environment; Human; Hygiene; Immune; Immune response; Immunity; Individual; Infection; Infectious Agent; Inflammation; Inflammatory; Interleukin-17; Lead; Link; Lung; Lung diseases; Lymphocyte; Lymphoid; Lymphoid Tissue; Modeling; Molecular; Mus; Neonatal; Organ; Organogenesis; Pathology; Pathway interactions; Patients; Pneumonia; Population; Publishing; Pulmonary Pathology; Recruitment Activity; Regulation; Research Personnel; Respiratory System; Respiratory physiology; Respiratory tract structure; Role; Secondary to; Signal Pathway; Signal Transduction; Site; Small Intestines; Stromal Cells; Structure; Structure of aggregated lymphoid follicle of small intestine; T cell response; T-Lymphocyte; Testing; Tissue Embedding; Tumor Necrosis Factor-Beta; allergic airway disease; base; chemokine; cigarette smoke-induced; cigarette smoking; cytokine; disorder control; immune function; improved; interleukin-22; lymph nodes; microbial; neonatal exposure; neonate; pathogen; research study; respiratory; response; scaffold

DESCRIPTION (provided by applicant): Asthma and chronic obstructive pulmonary disease (COPD) are chronic inflammatory diseases of the lung. These diseases are characterized by pulmonary inflammation and poor respiratory function. The underlying mechanisms controlling these diseases are still being elucidated. Interestingly, COPD patients and in some cases asthma patients develop inducible Bronchus Associated Lymphoid Tissue (iBALT). Bronchus Associated Lymphoid Tissue (BALT) was considered by early investigators to be a mucosal secondary lymphoid tissue embedded in the walls of the large airways, similar to Peyer's patches in the small intestine. However, we now know that BALT is not constitutively present in all mammalian species, notably mice and humans, and is induced in response to microbial exposure or other types of pulmonary inflammation. Therefore, the inducible lymphoid tissues in the lung may be more properly referred to as tertiary or ectopic lymphoid tissues and we have coined the term inducible BALT (iBALT) to describe them. Once formed, iBALT is maintained in the lung for several months or even longer and acts as a secondary lymphoid tissue that supports primary and secondary B and T cell responses to pulmonary antigens and pathogens. Importantly, pulmonary immune responses that occur in the presence of iBALT often have dramatically different characteristics than those that occur in the absence of iBALT. Thus, prior exposures of the respiratory tract can lead to lung remodeling and the development of iBALT, which regulates subsequent pulmonary immune responses via poorly defined mechanisms. We now have preliminary data showing that iBALT requires IL-17 and IL-22-expressing T cells for its formation, suggesting that iBALT forms in response to and participates in Th17 immune responses. Given the important role for Th17 cells in pulmonary diseases like asthma and COPD and the dramatic effects that iBALT has on pulmonary immune function to infectious agents, we believe that it is important to define the cellular and molecular mechanisms that control iBALT formation and to determine the mechanisms by which iBALT regulates pulmonary immune responses in the context of inflammatory disease.

描述（由申请人提供）：哮喘和慢性阻塞性肺疾病（COPD）是肺部的慢性炎症性疾病。这些疾病的特点是肺部炎症和呼吸功能差。控制这些疾病的潜在机制仍在阐明中。有趣的是，慢性阻塞性肺病患者和某些情况下的哮喘患者会出现诱导性支气管相关淋巴组织（iBALT）。支气管相关淋巴组织（Bronchus Associated Lymphoid Tissue， BALT）被早期研究者认为是一种嵌埋在大气道壁上的粘膜次级淋巴组织，类似于小肠中的Peyer's斑块。然而，我们现在知道BALT并非存在于所有哺乳动物物种中，特别是小鼠和人类，并且是在微生物暴露或其他类型的肺部炎症的反应中诱导的。因此，肺中的诱导淋巴组织可以更恰当地称为三级或异位淋巴组织，我们创造了术语诱导淋巴组织（iBALT）来描述它们。一旦形成，iBALT在肺中维持数月甚至更长时间，并作为次级淋巴组织支持原发性和继发性B细胞和T细胞对肺抗原和病原体的反应。重要的是，在存在iBALT时发生的肺免疫反应通常与不存在iBALT时发生的肺免疫反应具有显著不同的特征。因此，先前的呼吸道暴露可导致肺重塑和iBALT的发展，iBALT通过不明确的机制调节随后的肺免疫反应。我们现在有初步的数据表明，iBALT的形成需要IL-17和il -22表达的T细胞，这表明iBALT的形成是对Th17免疫反应的响应和参与。鉴于Th17细胞在哮喘和COPD等肺部疾病中的重要作用，以及iBALT对肺部免疫功能对感染因子的显著影响，我们认为，确定控制iBALT形成的细胞和分子机制以及确定iBALT在炎症性疾病背景下调节肺免疫反应的机制非常重要。