Antigen Recognition at Epithelial Interphases

上皮间期的抗原识别

• 批准号: 9323383
• 负责人: HANS-CHRISTIAN REINECKER
• 金额: $ 69.39万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9323383
• 关键词: Adenovirus Infections; Antigens; Blood Circulation; CD4 Positive T Lymphocytes; Cell Differentiation process; Cells; ChIP-seq; Colitis; DNA Viruses; Dendritic Cells; Detection; Development; Dinucleoside Phosphates; Epithelial; Fenestrated Capillary; Genetic Transcription; Helper-Inducer T-Lymphocyte; Host Defense; Immune; Immune response; Immune system; Inflammation; Inflammatory Bowel Diseases; Inflammatory disease of the intestine; Interleukin-10; Interleukin-17; Interphase; Intestinal Mucosa; Intestines; Lamina Propria; Lipoproteins; Lymphatic System; Mediating; Mesentery; Mucosal Immune Responses; Mucositis; Mus; Nucleic Acids; Outcome; Pathway interactions; Periodicity; Peripheral; Proteins; Publishing; RNA; Regulation; Regulatory T-Lymphocyte; Reporter; Research Design; Role; Sampling; Shapes; Signal Induction; Signal Transduction; Site; Small Intestines; Source; Spleen; Surface; System; T cell differentiation; T cell response; T-Cell Activation; T-Lymphocyte; TLR2 gene; Viral; Virus Diseases; antigen processing; antimicrobial; antiviral immunity; base; cell motility; experimental study; fetal liver kinase-2; functional outcomes; genome-wide; kinase inhibitor; lymph nodes; macrophage; microbial; migration; pathogen; polarized cell; programs; promoter; public health relevance; response; transcriptome; transcriptome sequencing

DESCRIPTION (provided by applicant): This renewal application seeks support for the continuation of our studies designed to elucidate the regulatory programs of dendritic cell subsets that are required for antimicrobial host defenses in the intestine. We recently discovered a cellular circuitry, whereby mucosal DCs interact with the fenestrated capillary vessel system of the small intestine for the sampling of antigens that transition from the blood circulation through the lamina propria into the intestinal lymphatic system and the control of mucosal inflammation. The integration of luminal and circulatory antigen surveillance in the SI indicates that mucosal dendritic cells and macrophages could receive microbial signals that originate outside the intestine and that intestinal pathogen recognition could impact peripheral immune responses. The focus of this proposal will be the foreign nucleic acid recognition pathways in mucosal Zbtb46+ DCs that include distinct classical DC subsets that can induce IL-17 expressing T helper cells (Th17) cells in the mucosal immune system but also drive inducible T regulatory cell development and IL-10 expression. Defining these pivotal mechanisms is important for strategies that can control intestinal inflammation but also for the understanding of the impact of mucosal immune responses on the peripheral immune system and extra intestinal manifestation of inflammatory bowel diseases.

描述（由申请人提供）：此更新申请为继续我们的研究提供支持，旨在阐明肠道中抗菌宿主防御剂所需的树突状细胞子集的调节计划。我们最近发现了一个细胞回路，粘膜DC与小肠的毛细管血管系统相互作用，用于对抗原的采样，这些抗原从血液循环通过层过层过渡到肠道淋巴系统和粘膜炎症的控制。 Si中的腔和循环抗原监测的整合表明，粘膜树突状细胞和巨噬细胞可以接收起源于肠子以外的微生物信号，并且肠道病原体识别可能会影响周围免疫反应。该提案的重点将是粘膜ZBTB46+ DC中的外国核酸识别途径，其中包括不同的经典DC子集，这些DC子集可以诱导粘膜免疫系统中的IL-17表达T辅助细胞（TH17）细胞，但也驱动诱导性T稳定性细胞的发育和IL-10表达。定义这些关键机制对于可以控制肠道炎症的策略以及对理解的策略很重要 粘膜免疫反应对外周免疫系统和炎症性肠病的肠道表现的影响。

项目成果

Genotype-phenotype analysis of the CXCL16 p.Ala181Val polymorphism in inflammatory bowel disease.

炎症性肠病 CXCL16 p.Ala181Val 多态性的基因型-表型分析。

• DOI: 10.1016/j.clim.2007.11.016
• 发表时间: 2008
• 期刊: Clinical immunology (Orlando, Fla.)
• 作者: Seiderer,Julia;Dambacher,Julia;Leistner,Dorothea;Tillack,Cornelia;Glas,Jürgen;Niess,Jan-Hendrik;Pfennig,Simone;Jürgens,Matthias;Müller-Myhsok,Bertram;Göke,Burkhard;Ochsenkühn,Thomas;Lohse,Peter;Reinecker,Hans-Christian;Brand,Ste
• 通讯作者: Brand,Ste

MyD88-dependent TLR1/2 signals educate dendritic cells with gut-specific imprinting properties.

• DOI: 10.4049/jimmunol.1003740
• 发表时间: 2011-07-01
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Wang S;Villablanca EJ;De Calisto J;Gomes DC;Nguyen DD;Mizoguchi E;Kagan JC;Reinecker HC;Hacohen N;Nagler C;Xavier RJ;Rossi-Bergmann B;Chen YB;Blomhoff R;Snapper SB;Mora JR
• 通讯作者: Mora JR