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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

基本信息

批准号：
BB/H012559/1
负责人：
David Hume
金额：
$ 88.68万
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%2FH012559%2F1
关键词：
CSF1 IL34 function Macrophages Avian

项目摘要

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.

巨噬细胞是一种大的白细胞，是抵御病原体的第一道防线，但也参与了感染性和炎症性疾病的许多病理过程。巨噬细胞也是人体的细胞废物处理系统，它们在伤口愈合和正常发育的许多方面都是必需的。鸡之所以引起人们的兴趣，是因为它们是一种经济上重要的家畜物种，它们是研究发展的易处理的模型，而且它们是可能影响人类的疾病的媒介，包括导致食物中毒和禽流感的细菌。本项目旨在了解鸟类巨噬细胞的产生是如何被控制的，以及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）来促进胚胎中巨噬细胞的产生、迁移和功能。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需要的。为了解决这一假设，我们建议制造转基因动物，其中所有巨噬细胞都被荧光转基因标记，以便我们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正在发育的胚胎来检验这个假设，看看巨噬细胞的产生或位置是否可以改变，以及这是否会改变正常发育的过程。这些实验不容易在哺乳动物身上进行，因为胚胎无法进入子宫。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，也将深入了解正常发育，这可能与理解人类怀孕和发育缺陷有关。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Functional annotation of the T-cell immunoglobulin mucin family in birds.

DOI：
10.1111/imm.12607
发表时间：
2016-07
期刊：
Immunology
影响因子：
6.4
作者：
Hu T;Wu Z;Vervelde L;Rothwell L;Hume DA;Kaiser P
通讯作者：
Kaiser P

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)
影响因子：
0
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

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
影响因子：
0
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