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Placental chemokine compartmentalisation by atypical chemokine receptors.

非典型趋化因子受体对胎盘趋化因子的区室化。

基本信息

批准号：
MR/V010972/1
负责人：
Gerard Graham
金额：
$ 240.46万
依托单位：
University of Glasgow
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2021
资助国家：
英国
起止时间：
2021 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FV010972%2F1
关键词：
Placental chemokine compartmentalisation atypical receptors.

项目摘要

When we are bitten by an insect, or wounded, we set up inflammation precisely at the damaged site. This involves the recruitment of cells called white blood cells to the area, which destroy bugs and help heal wounds. These white blood cells must be able to find their way precisely to the damaged area and they do this using molecules called chemokines which are made wherever damage or infection occurs and which act as a 'beacon' to attract the white blood cells. Chemokines therefore help white blood cells find their way around the body. Chemokines are also important in embryonic development as white blood cells, and other key cells, have to move within the embryo for it to develop properly. In mammals, including humans, the embryonic and maternal blood are in contact. The maternal blood can contain chemokines, especially when the mother is infected or setting up inflammation. Therefore if these chemokines were able to pass from the mother to the embryo this might interfere with their precise functions in the embryo. We have been studying specialised molecules called atypical chemokine receptors. These molecules basically destroy chemokines and one of their main sites of expression is on cells called trophoblasts in the placenta, which sit right between the mother and the embryo. Basically these receptors destroy chemokines at the junction between the mother and the embryo and ensure that they do not enter the embryonic circulation and therefore interfere with key aspects of cell movement during development. What we wish to do now is to study this process in great detail using specialised mouse models. We hope to gain an understanding of how this process functions and what its importance is for embryo survival and adult immune and inflammatory function. We believe that insights from the study will be important for understanding aspects of the basis for miscarriage and for defects in the immune and inflammatory (and potentially neuro-cognitive) systems of newborn babies and adults.

当我们被昆虫叮咬或受伤时，我们会在受损的部位精确地制造炎症。这涉及到将被称为白血球的细胞招募到该地区，以消灭细菌并帮助愈合伤口。这些白细胞必须能够找到准确到达受损区域的方法，它们使用称为趋化因子的分子来做到这一点，趋化因子是在发生损害或感染的地方制造的，充当着吸引白细胞的“灯塔”。因此，趋化因子帮助白血球在体内找到自己的路。趋化因子在胚胎发育中也很重要，因为白细胞和其他关键细胞必须在胚胎内移动，才能正常发育。在哺乳动物中，包括人类在内，胚胎和母体的血液是接触的。母亲的血液中可能含有趋化因子，特别是当母亲受到感染或引发炎症时。因此，如果这些趋化因子能够从母亲传递到胚胎，这可能会干扰它们在胚胎中的确切功能。我们一直在研究被称为非典型趋化因子受体的特殊分子。这些分子基本上会破坏趋化因子，它们的主要表达部位之一是胎盘中称为滋养层细胞的细胞，滋养层细胞正好位于母亲和胚胎之间。基本上，这些受体破坏母亲和胚胎交界处的趋化因子，确保它们不会进入胚胎循环，从而干扰发育过程中细胞运动的关键方面。我们现在希望做的是使用专门的老鼠模型来非常详细地研究这一过程。我们希望了解这一过程是如何发挥作用的，以及它对胚胎存活和成人免疫和炎症功能的重要性。我们认为，这项研究的见解对于了解流产的基础以及新生儿和成年人的免疫和炎症(以及潜在的神经认知)系统缺陷的各个方面都很重要。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Establishing Mixed Neuronal and Glial Cell Cultures from Embryonic Mouse Brains to Study Infection and Innate Immunity

建立小鼠胚胎大脑的混合神经元和胶质细胞培养物以研究感染和先天免疫

DOI：
10.3791/65331
发表时间：
2023
期刊：
Journal of Visualized Experiments
影响因子：
0
作者：
Gamble A
通讯作者：
Gamble A

Inflammatory Chemokine Receptors Support Inflammatory Macrophage and Dendritic Cell Maturation.

DOI：
10.4049/immunohorizons.2200069
发表时间：
2022-11-01
期刊：
ImmunoHorizons
影响因子：
0
作者：
Bartolini, Robin;Medina-Ruiz, Laura;Graham, Gerard J
通讯作者：
Graham, Gerard J

M1/M2 macrophages and their overlaps - myth or reality?

DOI：
10.1042/cs20220531
发表时间：
2023-08-14
期刊：
Clinical science (London, England : 1979)
影响因子：
0
作者：
通讯作者：

Diverse myeloid cells are recruited to the developing and inflamed mammary gland.

DOI：
10.1111/imm.13430
发表时间：
2022-02
期刊：
Immunology
影响因子：
6.4
作者：
Wilson GJ;Fukuoka A;Vidler F;Graham GJ
通讯作者：
Graham GJ

Role of placental inflammatory mediators and growth factors in patients with rheumatic diseases with a focus on systemic sclerosis.

DOI：
10.1093/rheumatology/keaa782
发表时间：
2021-07-01
期刊：
Rheumatology (Oxford, England)
影响因子：
0
作者：
Motta F;Codullo V;Ramoni V;Cesari S;Ferrario G;Fiandrino G;Beneventi F;Rampello S;Johnsson H;Montecucco C;Graham GJ
通讯作者：
Graham GJ