Cellular and molecular mechanisms of block of dendritic cell development in growth factor receptor mutant mice

生长因子受体突变小鼠树突状细胞发育阻断的细胞和分子机制

• 批准号: 203326339
• 负责人: Professorin Dr. Claudia Waskow
• 金额: --
• 依托单位: Forschungsgruppe Regeneration in der Hämatopoese
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/203326339?language=en
• 关键词: Cellular; molecular; mechanisms; block; dendritic

Dendritic cells are immuno-modulatory cells that are crucial for the instigation of immune responses in benefit for health (pathogen defense) but also in disadvantage for health (autoimmunity). However, antigen presentation by non-activated dendritic cells induces tolerance to any antigen including self-antigens, suggesting that dendritic cell homeostasis is one putative mechanism that regulates instigation, length and intensity of immune reactions. Therefore, the identification of growth requirements supporting or suppressing the development and maintenance of dendritic cells in vivo holds the promise to understand cellular mechanisms regulating immune responses. It is to date unclear which growth requirements are necessary for normal dendritic cell development in vivo. We recently reported on the important role for the growth factor receptor fetal liver kinase 2 (Flk2) during final stages of dendritic cell development in peripheral lymphoid organs. We now generated near complete dendritic cell null mice and thereby identified the two crucial growth factor receptors for dendritic cell development in vivo. In this proposal we describe a research plan that aims at analyzing the cellular and molecular basis of this developmental defect and at linking defective dendritic cell homeostasis to the maintenance of tolerance during adult life.

树突状细胞是免疫调节细胞，其对于激发有益于健康（病原体防御）但也不利于健康（自身免疫）的免疫应答至关重要。然而，非活化树突状细胞的抗原呈递诱导对包括自身抗原在内的任何抗原的耐受性，这表明树突状细胞稳态是一种公认的调节免疫反应的激发、长度和强度的机制。因此，识别支持或抑制树突状细胞在体内的发育和维持的生长要求，有望了解调节免疫应答的细胞机制。目前尚不清楚体内正常树突状细胞发育所需的生长条件。我们最近报道了生长因子受体胎肝激酶2（Flk 2）在外周淋巴器官树突状细胞发育的最后阶段的重要作用。我们现在产生了几乎完全的树突状细胞无效小鼠，从而确定了体内树突状细胞发育的两个关键生长因子受体。在这个建议中，我们描述了一个研究计划，旨在分析这种发育缺陷的细胞和分子基础，并在连接缺陷的树突状细胞的稳态，以维持在成年期的耐受性。