Pulmonary Interactions with Innate Immunity

肺部与先天免疫的相互作用

• 批准号: 7878442
• 负责人: Patricia W Finn
• 金额: $ 2.18万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-14 至 2010-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7878442
• 关键词: Adoptive Transfer; Allergic; Animal Model; Anti-Inflammatory Agents; Anti-inflammatory; Antibodies; Antigens; Asthma; Binding; Biochemical; Biological; Biological Assay; Blocking Antibodies; Carbohydrates; Cell Communication; Cells; Collectins; Cytotoxic T-Lymphocyte-Associated Protein 4; Data; Development; Disease; EMSA; Epidemic; Extrinsic asthma; Human; Immune; Immune response; Immunity; Immunosuppressive Agents; Incidence; Inflammation; Inflammatory; Interleukin-17; Investigation; Lead; Length; Lung; Lymphocyte antigen; Mediating; Mediator of activation protein; Modeling; Molecular; Mus; Natural Immunity; Neck; Pathway interactions; Play; Prevention; Pulmonary Surfactant-Associated Protein D; Recombinants; Regulation; Reporter Genes; Role; Sampling; Scanning; Signal Pathway; Site; Structure; T-Cell Activation; T-Cell Receptor; T-Lymphocyte; T-Lymphocyte Subsets; Therapeutic Intervention; cytokine; cytotoxic; glycoprotein 340; in vivo; inhibitor/antagonist; insight; mutant; pathogen; public health relevance; receptor; response; surfactant; transcription factor

DESCRIPTION (provided by applicant): Asthma incidence is increasing and warrants investigation of distinct immune mechanisms. Innate, non- antigen-dependent immunity has been shown to play a role in allergic responses. Our data suggest that the innate immune collectin, surfactant (SP-)-D, can function as an endogenous, anti-inflammatory regulator of allergic responses. We analyze T cell and SP-D interactions, and focus on T helper (Th) 17 T cells. Also, we investigate evidence that cytotoxic t-lymphocyte antigen 4 (CTLA4), an inhibitor of T cells, mediates SP-D effects. Our data indicate that SP-D diminishes IL-17 responses while increasing CTLA4. Our overall hypothesis is that SP-D is an endogenous regulator of immunity that decreases allergic inflammation by inducing immunosuppressive pathways within T cells. Aim 1 will investigate the mechanisms of SP-D modulation of T cell subsets. Aim 2 will analyze the biochemical and cellular mechanisms of SP-D binding to T cells. Aim 3 will focus on SP-D-dependent molecular mechanisms regulating CTLA4 expression. Aim 4 will investigate the response of T cell subsets to SP-D in cells obtained from asthmatic subjects. An anti-inflammatory role for SP-D, specifically in T cell activation, reveals a distinct pathway for potential therapeutic intervention in T cell mediated disorders. This proposal will examine biochemical and biological pathways that may lead to the development of candidates for therapeutic intervention for asthma. PUBLIC HEALTH RELEVANCE: Allergic asthma has become an epidemic in many parts of the world, and compels investigation of alternative strategies. We will focus on immune pathways that are not classically associated with asthma, but may uncover new insights into the prevention or treatment of asthma. We will examine the roles of immune molecule in decreasing immune responses, including immune (T cell) activation in an animal model of asthma and with samples from human asthmatics.

描述（由申请人提供）：哮喘发病率正在增加，需要研究不同的免疫机制。先天的、非抗原依赖性免疫已被证明在过敏反应中起作用。我们的数据表明，先天性免疫凝集素，表面活性剂（SP-）-D，可以作为一个内源性的，抗炎调节过敏反应。我们分析了T细胞和SP-D的相互作用，并专注于T辅助细胞（Th）17 T细胞。此外，我们调查的证据表明，细胞毒性T淋巴细胞抗原4（CTLA 4），T细胞的抑制剂，介导SP-D的影响。我们的数据表明，SP-D减少IL-17反应，同时增加CTLA 4。我们的总体假设是SP-D是一种内源性免疫调节剂，通过诱导T细胞内的免疫抑制途径来减少过敏性炎症。目的1探讨SP-D对T细胞亚群的调节机制。目的2分析SP-D与T细胞结合的生化和细胞机制。目的3：探讨SP-D依赖性CTLA 4表达调控的分子机制。目的4研究哮喘患者T细胞亚群对SP-D的反应。SP-D的抗炎作用，特别是在T细胞活化中，揭示了T细胞介导的疾病中潜在治疗干预的独特途径。该提案将研究可能导致哮喘治疗干预候选人发展的生物化学和生物学途径。公共卫生相关性：过敏性哮喘已成为世界许多地区的流行病，并迫使研究替代策略。我们将重点关注与哮喘无关的免疫途径，但可能会发现预防或治疗哮喘的新见解。我们将研究免疫分子在降低免疫反应中的作用，包括哮喘动物模型和人类哮喘患者样本中的免疫（T细胞）激活。