Control of Langerhans Cell Development

朗格汉斯细胞发育的控制

• 批准号: 7207927
• 负责人: David Kim Burnham
• 金额: $ 3.4万
• 依托单位: OKLAHOMA STATE UNIVERSITY STILLWATER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7207927
• 关键词: CD34 molecule; Langerhans' cell; T lymphocyte; antigens; biological signal transduction; cell cycle; cell growth regulation; cell proliferation; cytokine; cytokine receptors; enzyme linked immunosorbent assay; flow cytometry; genetically modified animals; immune response; laboratory mouse; phenotype; skin; thymus

DESCRIPTION (provided by applicant): As the resident dendritic cells of mammalian epidermis, Langerhans' cells (LC) function as sentinels capable of initiating immune responses that protect the skin against infectious agents and cancer. In order to do so, LC take up and process foreign antigens within the epidermis prior to migrating to draining lymph nodes where they present these antigens to thymus derived lymphocytes. To maintain LC levels within the epidermis, these cells must be replenished from CD34+ precursors that enter the skin from the peripheral blood. Unfortunately, most of what is known about the development of LC comes from in vitro studies that may or may not be relevant to what occurs within the intact organism. However, the small amount of in vivo evidence that exists, suggests that requirements for the development of LC are unique as compared to those for other types of dendritic cells. The purpose of this study is to assess the role of cytokines/chemokines in this replenishment process in vivo. This will be done by analyzing the rate of recovery of LC and their phenotype in cytokine/chemokine gene knockout and transgenic mice following depletion of LC by topical LPS application. The results of these studies will likely improve our ability to modulate immune responses at their earliest phases by controlling LC development.

描述（由申请人提供）： 作为哺乳动物表皮的驻形树突状细胞，兰格汉斯细胞（LC）的发挥作用是能够启动免疫反应的前哨，可保护皮肤免受传染性剂和癌症的影响。为此，LC在迁移到排水淋巴结之前，在表皮内进行外抗原，在那里它们将这些抗原呈现给胸腺衍生的淋巴细胞。为了维持表皮中的LC水平，必须从从外周血进入皮肤的CD34+前体中补充这些细胞。不幸的是，关于LC发展的大多数知识都来自体外研究，这些研究可能与完整生物体中发生的情况可能无关。但是，存在少量的体内证据，表明与其他类型的树突状细胞相比，LC的发展的要求是独一无二的。这项研究的目的是评估细胞因子/趋化因子在体内补充过程中的作用。这将通过分析局部LPS应用LC耗尽后的细胞因子/趋化因子基因敲除和转基因小鼠的LC恢复速率及其在细胞因子基因敲除和转基因小鼠中的回收率来完成。这些研究的结果可能会提高我们通过控制LC开发在最早的阶段调节免疫反应的能力。