Regulation of tissue resident macrophages during mammary gland development

项目总结 乳腺发育需要乳腺上皮细胞和细胞之间复杂的相互作用 它们周围的环境。组织驻留巨噬细胞近距离存在于乳腺中。 与发育中的上皮结构和脂肪间质内相关，并被认为是重要的 有助于乳腺发育和维持组织动态平衡。了解这些 机制是决定巨噬细胞功能改变对丢失的后果的关键 动态平衡和促进特定组织的疾病，如肿瘤的发生。这个项目的目标是 描述维持乳腺组织内巨噬细胞内环境平衡的机制 并确定这些机制的改变是否会影响乳腺发育。在……里面 初步研究，我们开发了一种新的方法来识别和隔离不同的种群 来自乳腺的常驻巨噬细胞，包括与上皮结构相关的巨噬细胞 以及与间质区域相关的那些。在前期研究的基础上，我们提出了信号换能器 转录激活子(STAT)通路是乳腺内驻留巨噬细胞的关键调节因子 而这些途径的解除调控导致巨噬细胞的形成，从而产生一种 允许肿瘤发生的环境。拟议的研究将1)确定来源和本地化 乳腺发育过程中的组织驻留巨噬细胞群，2)论证了 STATS作为乳腺中组织驻留巨噬细胞的关键转录调节因子和3) 确定炎症因子对乳腺内滞留巨噬细胞功能的影响。近期 研究的重点是了解推动组织驻留巨噬细胞功能的机制及其 对组织发育和动态平衡的贡献。然而，人们对此知之甚少 驱动乳腺内驻留巨噬细胞功能的机制。了解这些机制 将深入了解驻留巨噬细胞的功能变化，如局部或全身的变化 炎症信号，影响上皮细胞的形态形成，并导致癌症风险。

PROJECT SUMMARY Mammary gland development requires complex interactions between mammary epithelial cells and their surrounding environment. Tissue resident macrophages are present in the mammary gland in close association with developing epithelial structures and within the adipose stroma, and are known to be important for contributing to mammary gland development and maintaining tissue homeostasis. Understanding these mechanisms is critical for determining the consequences of altered macrophage function on loss of homeostasis and promotion of tissue specific disease, such as tumorigenesis. The goal of this project is to delineate the mechanisms that maintain tissue resident macrophages in the mammary gland in a homeostatic state and to determine whether the altering these mechanisms impacts mammary gland development. In preliminary studies, we have developed a novel method for identifying and isolating distinct populations of resident macrophages from the mammary gland, including macrophages associated with epithelial structures and those associated with stromal regions. Based on preliminary studies, we propose that signal transducer and activator of transcription (STAT) pathways are key regulators of resident macrophages in the mammary gland and that deregulation of these pathways results in the formation of macrophages that create a permissive environment for tumorigenesis. Proposed studies will 1) determine the source and localization of tissue resident macrophage populations during mammary gland development, 2) demonstrate the importance of STATs as key transcriptional regulators of tissue resident macrophages in the mammary gland and 3) determine the effects of inflammatory factors on resident macrophage function in the mammary gland. Recent studies have focused on understanding the mechanisms driving tissue resident macrophage function and their contributions to tissue development and homeostasis. However, relatively little is known regarding the mechanisms driving resident macrophage function in the mammary gland. Understanding these mechanisms will provide insights into how alterations in resident macrophage function, such as by local or systemic inflammatory signals, impact epithelial morphogenesis and contribute to cancer risk.