IgA inducing peptide

IgA诱导肽

• 批准号: 6904672
• 负责人: Don MARK ESTES
• 金额: $ 15.1万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-15 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6904672
• 关键词: B lymphocyte; T lymphocyte; cell differentiation; clinical research; dendritic cells; enzyme linked immunosorbent assay; flow cytometry; gene expression; gene induction /repression; genetic regulation; growth factor; human subject; immune response; immunodeficiency; immunogenetics; immunoglobulin A; immunomagnetic separation; macrophage; monocyte; peptides; protein localization

DESCRIPTION (provided by applicant): IgA is the predominant Ig isotype in mucosal secretions of most mammalian species and is thus ideally localized to prevent pathogen entry. We took advantage of the large quantities of mucosal tissues, including lymph nodes and Peyer's patches in cattle to develop a cDNA library to probe for factors that regulate IgA expression. We identified a novel factor in the bovine, which impacts IgA production in vito and designated the factor, IgA Inducing Protein or IGIP. The general goal of this two-year innovative proposal is to extend our studies of this novel factor to humans and to elucidate the mechanisms by which IGIP influences IgA production. Our working hypothesis for the project is that interstitial dendritic cell derived- IGIP is conserved across mammalian species and is an essential component of T-dependent and independent pathways for induction of IgA-expressing cells. We also hypothesize that altered IGIP regulation in dendritic cells and/or B cells is a factor in selective IgA deficiency. The specific aims that will test this hypothesis are: 1) Use an established in vitro model to determine the role of IGIP in differentiation of IgA-expressing human B cells; 2) Identify the cellular sources of IGIP transcripts and protein in peripheral blood leukocytes including dendritic cells, T cells, B cells and monocyte/macrophages from normal individuals; 3) Compare the expression of IGIP transcripts and protein and the responsiveness to IGIP of peripheral blood leukocytes from patients with selective IgA deficiency. The proposed studies will be the first to establish the mechanism(s) by which a unique, recently identified factor acts in concert with known factors such as TGF-beta or IL-10 to promote IgA responses and should help clarify the role of human DC in the regulation of the IgA responses. In addition, the proposed studies will begin to examine determine the potential relationship between IGIP and clinical abnormality in IgA production.

描述（由申请人提供）：IgA 是大多数哺乳动物物种粘膜分泌物中的主要 Ig 同种型，因此理想地定位以防止病原体进入。我们利用大量的粘膜组织，包括牛的淋巴结和派尔氏集结，开发了一个 cDNA 文库来探测调节 IgA 表达的因素。我们在牛体内发现了一种影响 IgA 体外产生的新因子，并将该因子命名为 IgA 诱导蛋白或 IGIP。这项为期两年的创新提案的总体目标是将我们对这种新因子的研究扩展到人类，并阐明 IGIP 影响 IgA 产生的机制。我们对该项目的工作假设是，间质树突细胞衍生的 IGIP 在哺乳动物物种中是保守的，并且是诱导 IgA 表达细胞的 T 依赖性和独立途径的重要组成部分。我们还假设树突状细胞和/或 B 细胞中 IGIP 调节的改变是选择性 IgA 缺乏的一个因素。检验这一假设的具体目标是： 1) 使用已建立的体外模型来确定 IGIP 在表达 IgA 的人类 B 细胞分化中的作用； 2）鉴定正常个体外周血白细胞（包括树突状细胞、T细胞、B细胞和单核/巨噬细胞）中IGIP转录本和蛋白质的细胞来源； 3)比较选择性IgA缺乏症患者外周血白细胞IGIP转录物和蛋白的表达以及对IGIP的反应性。拟议的研究将首次建立一种独特的、最近发现的因子与已知因子（如 TGF-β 或 IL-10）协同作用以促进 IgA 反应的机制，并应有助于阐明人类 DC 的作用IgA 反应的调节。此外，拟议的研究将开始确定 IGIP 与 IgA 产生临床异常之间的潜在关系。

项目成果

Human IgA-inducing protein from dendritic cells induces IgA production by naive IgD+ B cells.

• DOI: 10.4049/jimmunol.0801973
• 发表时间: 2009-02-15
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Endsley MA;Njongmeta LM;Shell E;Ryan MW;Indrikovs AJ;Ulualp S;Goldblum RM;Mwangi W;Estes DM
• 通讯作者: Estes DM