Role of epididymal dendritic cells in male reproductive function

附睾树突状细胞在男性生殖功能中的作用

基本信息

  • 批准号:
    8469327
  • 负责人:
  • 金额:
    $ 35.21万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2011
  • 资助国家:
    美国
  • 起止时间:
    2011-08-12 至 2016-05-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Infection or inflammation of the male reproductive tract often lead to permanent infertility. Yet, one of the most understudied aspects of male reproductive physiology is the ability of the excurrent duct to protect maturing spermatozoa against an autoimmune response, while initiating very efficient immune activation against pathogens. The present application is based on our new discovery that a dense dendritic cell network populates the epididymis. We showed that epididymal dendritic cells (eDCs) establish intimate interactions with the epididymal mucosa and can send dendritic projections between epithelial cells toward the lumen. eDCs have the ability to present antigens to CD4+ and CD8+ T cels in vitro. We hypothesize that eDCs can interact with the luminal content, including spermatozoa, and regulate the balance between immune tolerance and inflammation. Aim 1a wil characterize eDCs using high resolution imaging in CD11c-EYFP and CX3CR1-GFP transgenic mice, comparative flow cytometry analysis and antigen-presenting assays before, during and after puberty. We postulate that the eDC network is reorganized during puberty, when sperm begin populating the excurrent duct. Aim 1b wil examine the regional specificities of eDC subsets in the context of the dual function of the epididymis. eDCs will be isolated from the proximal epididymal region (primarily involved in sperm maturation and protection against an autoimmune response), and distal region (more susceptible to infections by ascending pathogens). Comparative flow cytometry analysis and antigen-presenting capability will be determined in proximal and distal eDC populations. Aim 2 wil determine the role of eDCs in the homeostatic and inflamed mouse epididymis, using conventional fluorescence and intravital multiphoton microscopy, and flow cytometry analysis. Aim 2a wil test the hypothesis that eDCs have the ability to sample and process luminal antigens including those present in sperm. Aim 2b will analyze the behavior of eDCs in the epididymis after injection with LPS (to mimic infections), vasectomy (downstream blockade of luminal flow) or efferent duct ligation (upstream blockade of luminal flow). The goal of this application is to characterize the nature and functions of the eDC network to provide new frameworks for the treatment of male immunological infertility (which is a major public health issue) and, ultimately, for the control of male fertility.
描述(由申请人提供):男性生殖道感染或炎症往往导致永久性不育。然而,男性生殖生理学中最未充分研究的方面之一是流出道保护成熟精子免受自身免疫反应的能力,同时启动非常有效的免疫激活以对抗病原体。本申请是基于我们的新发现,即密集的树突状细胞网络填充附睾。我们发现,附睾树突状细胞(eDCs)与附睾粘膜建立了密切的相互作用,并可以向管腔发送上皮细胞之间的树突状突起。eDC具有在体外向CD 4+和CD 8 + T细胞呈递抗原的能力。我们假设eDCs可以与管腔内容物(包括精子)相互作用,并调节免疫耐受和炎症之间的平衡。目的1a在CD 11 c-EYFP和CX 3CR 1-GFP转基因小鼠中使用高分辨率成像、比较流式细胞术分析和抗原呈递分析来表征青春期之前、期间和之后的eDCs。我们假设,eDC网络在青春期重组,当精子开始填充流出道。目的1b将在附睾双重功能的背景下检查eDC亚群的区域特异性。eDC将从近侧附睾区域(主要涉及精子成熟和针对自身免疫应答的保护)和远侧区域(更容易受到上行病原体的感染)分离。将在近端和远端eDC群体中确定比较流式细胞术分析和抗原呈递能力。目的2利用常规荧光显微镜、活体多光子显微镜和流式细胞术分析,探讨eDCs在稳态和炎症小鼠附睾中的作用。目的2a将检验eDC具有采样和处理管腔抗原(包括存在于精子中的那些)的能力的假设。目的2b将分析在注射LPS(模拟感染)、输精管切除术(管腔流动的下游阻断)或输出管结扎(管腔流动的上游阻断)后附睾中eDC的行为。本申请的目标是描述eDC网络的性质和功能,为治疗男性免疫性不育(这是一个主要的公共卫生问题)提供新的框架,并最终控制男性生育力。

项目成果

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Nicolas Da Silva其他文献

Nicolas Da Silva的其他文献

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{{ truncateString('Nicolas Da Silva', 18)}}的其他基金

Role of epididymal dendritic cells in male reproductive function
附睾树突状细胞在男性生殖功能中的作用
  • 批准号:
    8318556
  • 财政年份:
    2011
  • 资助金额:
    $ 35.21万
  • 项目类别:
Role of epididymal dendritic cells in male reproductive function
附睾树突状细胞在男性生殖功能中的作用
  • 批准号:
    8158869
  • 财政年份:
    2011
  • 资助金额:
    $ 35.21万
  • 项目类别:
Role of epididymal dendritic cells in male reproductive function
附睾树突状细胞在男性生殖功能中的作用
  • 批准号:
    8675751
  • 财政年份:
    2011
  • 资助金额:
    $ 35.21万
  • 项目类别:

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