CSF1 IL34 and the function of macrophages in avian development

CSF1 IL34 和巨噬细胞在禽类发育中的功能

• 批准号: BB/H012745/1
• 负责人: Peter Kaiser
• 金额: $ 8.97万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FH012745%2F1
• 关键词: CSF1; IL34; function; macrophages; avian

Macrophages are large white blood cells that are the first line of defense against pathogens, but also contribute to much of the pathology of infectious and inflammatory disease. Macrophages are also the bodies cellular waste disposal system, and they are needed for wound healing and for many aspects of normal development. Chickens are of interest because they are an economically important livestock species, they are tractable model in which to study development, and they are vectors for diseases that can affect humans including bacteria that cause food poisoning and avian influenza. This project aims to understand how the production of macrophages is controlled in birds and the function of macrophages in embryonic development. Our hypothesis is that two growth factors, macrophage colony-stimulating factor (CSF-1) and interleukin 34 (IL-34) act through a common receptor (the CSF-1 receptor) to promote the production, migration and function of macrophages in an embryo. In turn, the macrophages are needed for the normal process of organ formation and overall growth in the embryo. To address this hypothesis, we propose to make transgenic animals in which all of the macrophages are tagged with a fluorescent transgene so we can monitor when they appear and how they move about in the embryo. We will make the two growth factors as recombinant proteins, and make antibodies that prevent their actions. And finally, we will test the hypothesis by introducing the factors, or antibodies, into the developing embryo in the egg, to see whether macrophage production or location can be altered, and whether this changes the course of normal development. These are experiments that cannot be done easily in mammals, because the embryo cannot be access in the uterus. If our hypothesis is correct, we will identify candidate modulators of chicken immunity and growth, and also gain an insight into normal development that might be relevant to understanding human pregnancy and developmental defects.

巨噬细胞是大的白色血细胞，它们是抵抗病原体的第一道防线，但也有助于感染性和炎性疾病的大部分病理学。巨噬细胞也是身体的细胞废物处理系统，它们是伤口愈合和正常发育的许多方面所必需的。鸡之所以令人感兴趣，是因为它们是经济上重要的牲畜物种，它们是研究发育的易处理模型，并且它们是可能影响人类的疾病的媒介，包括引起食物中毒和禽流感的细菌。该项目旨在了解巨噬细胞的产生是如何控制在鸟类和巨噬细胞在胚胎发育中的功能。我们的假设是，两种生长因子，巨噬细胞集落刺激因子（CSF-1）和白细胞介素34（IL-34）通过一个共同的受体（CSF-1受体），以促进生产，迁移和巨噬细胞在胚胎中的功能。反过来，巨噬细胞是胚胎器官形成和整体生长的正常过程所必需的。为了解决这个假设，我们建议制造转基因动物，其中所有的巨噬细胞都用荧光转基因标记，这样我们就可以监测它们何时出现以及它们如何在胚胎中移动。我们将把这两种生长因子制成重组蛋白，并制造抗体来阻止它们的作用。最后，我们将通过将这些因子或抗体引入卵子中发育中的胚胎来验证这一假设，看看巨噬细胞的产生或位置是否会改变，以及这是否会改变正常发育的过程。这些实验在哺乳动物中不容易完成，因为胚胎不能在子宫中进入。如果我们的假设是正确的，我们将确定鸡免疫和生长的候选调节剂，并深入了解可能与理解人类妊娠和发育缺陷有关的正常发育。

项目成果

IL-4 directly signals tissue-resident macrophages to proliferate beyond homeostatic levels controlled by CSF-1.

• DOI: 10.1084/jem.20121999
• 发表时间: 2013-10-21
• 期刊: The Journal of experimental medicine
• 作者: Jenkins SJ;Ruckerl D;Thomas GD;Hewitson JP;Duncan S;Brombacher F;Maizels RM;Hume DA;Allen JE
• 通讯作者: Allen JE

Visualisation of chicken macrophages using transgenic reporter genes: insights into the development of the avian macrophage lineage.

• DOI: 10.1242/dev.105593
• 发表时间: 2014-08
• 期刊: Development (Cambridge, England)
• 作者: Balic A;Garcia-Morales C;Vervelde L;Gilhooley H;Sherman A;Garceau V;Gutowska MW;Burt DW;Kaiser P;Hume DA;Sang HM
• 通讯作者: Sang HM

Antigen Sampling CSF1R-Expressing Epithelial Cells Are the Functional Equivalents of Mammalian M Cells in the Avian Follicle-Associated Epithelium

• DOI: 10.3389/fimmu.2019.02495
• 发表时间: 2019-10-22
• 期刊: FRONTIERS IN IMMUNOLOGY
• 影响因子: 7.3
• 作者: Balic, Adam;Chintoan-Uta, Cosmin;Vervelde, Lonneke
• 通讯作者: Vervelde, Lonneke