FoxP3+ T cells of mucosal tissues

粘膜组织的 FoxP3 T 细胞

• 批准号: 7762174
• 负责人: CHANG H KIM
• 金额: $ 33.21万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-01 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7762174
• 关键词: AKR/J Mouse; Acne Vulgaris; Address; Adoptive Transfer; Adult; Agonist; All-Trans-Retinol; Animal Model; Antibody Formation; Antigens; Area; Autoimmunity; Autologous; B-Lymphocytes; Biological; Biological Assay; Biological Markers; CD4 Positive T Lymphocytes; Cell Differentiation process; Cells; Cellular biology; Chemopreventive Agent; Data; Development; Diet; Disease; Dose; Dysplasia; Epithelial; Fortified Food; Gastroenterology; Generations; Goals; Hand functions; Health; Homing; Homing Behavior; Human; Immune; Immune System Diseases; Immune response; Immune system; Immunity; In Vitro; Incidence; Inflammation; Inflammatory; Inflammatory Response; Inflammatory disease of the intestine; Intestines; Lamina Propria; Lead; Link; Lung; Malignant Neoplasms; Modeling; Molecular; Mucous Membrane; Mus; Outcome; Pathway interactions; Play; Population; Prevention; Principal Investigator; Published Comment; Regulation; Regulatory T-Lymphocyte; Research; Research Design; Research Personnel; Resources; Retinoid Receptor; Retinoids; Risk; Role; Serum; Site; Small Intestines; Solid; Sorting - Cell Movement; Structure of aggregated lymphoid follicle of small intestine; Supplementation; Suppressor-Effector T-Lymphocytes; T memory cell; T-Lymphocyte; T-Lymphocyte Subsets; Testing; Therapeutic; Tissues; Tonsil; Transcriptional Regulation; Tretinoin; Umbilical Cord Blood; Vitamin A; Vitamin A Deficiency; Work; base; cancer cell; cancer epidemiology; cancer type; cell killing; cell motility; clinical application; dietary supplements; experience; feeding; food consumption; in vivo; migration; novel; novel strategies; peripheral blood; prevent; programs; public health relevance; receptor; research study; response; tissue tropism; trafficking; transcription factor

DESCRIPTION (provided by applicant): Vitamin A (retinol) and its metabolites (called retinoids) play critical roles in the immune system. Retinoids regulate the development and functions of various types of immune cells and are being used as therapeutics for some inflammatory diseases and cancers. There is a strong body of evidence that vitamin A metabolites play both positive and negative roles in regulation of the immune system, and we still do not clearly understand how they function in both ways. The overall objective of this research is to elucidate the role of retinoids in generation of FoxP3+ regulatory T cells in mucosal tissues in vitro and in vivo and to determine the functional significance of this novel biological pathway. FoxP3+ regulatory T cells are a major subset of T cells specialized in suppression of autoimmunity and over-active immune responses. Our central hypothesis is that retinoids are natural inducers of FoxP3+ cells that are specialized in regulation of immune responses in mucosal tissues. This hypothesis is based upon our strong preliminary data showing that retinoids induce the master transcription factor FoxP3 in T cells. We also found that the retinoid-induced FoxP3+ cells are unique in that they express mucosal tissue homing receptors and several effector molecules associated with target cell killing. Our rationale for this project is that its successful completion may well provide a mechanism important for our understanding of the role of retinoids as natural regulators of immune responses. This application has three specific aims: Specific aim #1: Establish retinoids as natural inducers of a mucosal FoxP3+ regulatory T-cell subset. Specific aim #2: Determine the molecular basis of the tissue tropism of retinoid-induced mucosal homing FoxP3+ T cells. Specific aim #3: Investigate the impact of retinoid-induced FoxP3+ T cells on regulation of immune responses and inflammation in mucosal tissues. Following the successful completion of the proposed research, we expect to 1) have identified a novel mechanism by which vitamin A metabolites regulate the immune system; 2) have determined the important trafficking receptors of retinoid-induced FoxP3+ T cells; and 3) have identified novel strategies by which we can control inflammatory diseases in selected mucosal tissues through the use of vitamin A/retinoids and retinoid-induced FoxP3+ T cells. PUBLIC HEALTH RELEVANCE: We will study how vitamin A and its metabolites promote the generation of T cells important for regulation of immune responses. The outcomes of this project would significantly advance our understanding of the generation of important regulatory T cell subsets in mucosal tissues and of the roles of vitamin A and retinoids in regulation of the immunity and inflammatory diseases. Since vitamin A is widely consumed by humans, the impact of the project on human health will be high.

描述（由申请人提供）：维生素A（视黄醇）及其代谢产物（称为视黄醇）在免疫系统中起关键作用。类维生素类似于各种免疫细胞的发育和功能，并被用作某些炎症性疾病和癌症的治疗剂。有大量证据表明，维生素A代谢产物在免疫系统的调节中既有正面和负作用，我们仍然没有清楚地了解它们在这两种方面的功能。这项研究的总体目的是阐明类视黄素在体外和体内粘膜组织中FOXP3+调节T细胞产生中的作用，并确定这种新型生物学途径的功能意义。 FOXP3+调节性T细胞是专门抑制自身免疫性和过度活跃免疫反应的T细胞的主要子集。我们的中心假设是类视黄素是FOXP3+细胞的天然诱导剂，专门调节粘膜组织中的免疫反应。该假设是基于我们强大的初步数据，表明类维生素类动物在T细胞中诱导主转录因子FOXP3。我们还发现，类维生素性诱导的FOXP3+细胞是独一无二的，因为它们表达粘膜组织寄养受体以及与靶细胞杀死相关的几种效应分子。我们对该项目的理由是，它的成功完成可能会为我们理解类维生素类动物作为免疫反应的自然调节剂的作用提供重要的机制。该应用具有三个特定的目的：特定目标＃1：将类维生素类似于粘膜FOXP3+调节性T细胞子集的天然诱导剂。特定目的＃2：确定性类维生素类动物诱导的粘膜归巢FOXP3+ T细胞的组织向量的分子基础。具体目的＃3：研究类维生素性诱导的FOXP3+ T细胞对粘膜组织免疫反应和炎症调节的影响。在拟议的研究成功完成后，我们期望1）确定了一种新型机制，维生素A代谢物通过该机制调节免疫系统； 2）已经确定了类维生素性诱导的FOXP3+ T细胞的重要运输受体； 3）已经确定了新的策略，通过使用维生素A/类维生素类动物和类维生素性诱导的FOXP3+ T细胞，我们可以通过这些策略来控制选定的粘膜组织中的炎症性疾病。 公共卫生相关性：我们将研究维生素A及其代谢产物如何促进T细胞的产生对于调节免疫反应的重要性。该项目的结果将大大提高我们对粘膜组织中重要调节性T细胞亚群以及维生素A和类视黄素在调节免疫和炎症性疾病调节中的作用的理解。由于维生素A被人类广泛消耗，因此该项目对人类健康的影响将很高。