RORgamma+ Innate Lymphoid Cells in Skin Wound Healing
RORgamma+ Innate Lymphoid Cells in Skin Wound Healing
批准号:
MR/K021125/1
负责人:
Mark Coles
金额:
$53.4万
依托单位:
依托单位国家:
英国
项目类别:
Research Grant
财政年份:
2014
资助国家:
英国
项目状态:
已结题
起止时间:
2014 至 --
中文摘要
正常的伤口愈合在体内不断发生,在维持正常的健康和健身中起着关键作用。最近有研究表明,肠道中一种特殊类型的免疫细胞,即先天淋巴样细胞,在维持正常肠道功能方面起着关键作用。我们发现,这些细胞可以移动到皮肤上,在伤口和擦伤的正常愈合中起着关键作用。这是通过防止“适应性”免疫细胞T淋巴细胞在伤口中诱导疤痕样组织来实现的。当正常愈合不能正常发生时,会引起疼痛和难以治疗的病理,因此需要更好地了解正常伤口愈合的过程。在这项研究计划中,我们将分析协调正常愈合过程的信号,以及这些信号是如何被调节的,从而使伤口快速愈合而不留下毁容。我们将确定免疫细胞如何被招募到伤口部位,以及当伤口完全愈合时它们会发生什么。我们将分析不同的细胞如何相互沟通,以及这些信号的时间如何控制正常的愈合过程。我们将研究这一过程是如何被可能感染伤口的机会性细菌调节的,以及这是如何改变伤口愈合过程的。通过与临床样本和工业合作者的合作,我们将努力将这项研究的结果转化为临床。传统上,免疫系统被描绘成一支随时准备消灭入侵细菌和病毒的军队。我们的初步数据表明,免疫细胞的一个子集应被视为“治疗者”而不是“士兵”,在维持正常伤口愈合方面发挥特殊作用。通过了解免疫细胞如何控制皮肤屏障的功能和修复,将有助于开发新的治疗炎症性皮肤疾病和溃疡性病变的方法,这是尚未解决的重大医学挑战。
英文摘要
Normal wound healing is continually occurring in the body and has a key role in maintaining normal health and fitness. Recently it has been shown in the intestine that a specialised type of immune cells called innate lymphoid cells have a key role in maintaining normal gut function. We have found that these cells can travel to the skin have a key role in the normal healing of cuts and abrasions. This occurs through preventing the "adaptive" immune cells, T lymphocytes from causing the induction of scar like tissue in wounds. When normal healing fails to occur properly it can induce painful and difficult to treat pathologies, thus the need to better understand the process of normal wound healing. In this research proposal we will analyse the signals that orchestrate the normal healing process and how these are regulated so wounds heal quickly without leaving disfiguration. We will determine how immune cells are recruited to the wound sites and what happens to them when wounds are fully healed. We will analyse how the different cells communicate with each other and how the timing of these signals controls the normal healing process. We will investigate how this process can be modulated by the presence of opportunistic bacteria that can infect wounds and how this changes the wound healing process. Through working with clinical samples and industrial collaborators we will work towards translating the results of this research into the clinic.Conventionally the immune system is portrayed as an army of soldiers ready to destroy invading bacteria and viruses. Our preliminary data suggest that a subset of immune cells should be seen as "healers" rather than "soldiers", with a special role in maintaining normal wound healing. Through understanding how the immune cells controls the function and repair of the skin barrier will help in the development of new treatments for inflammatory skin disorders and ulcerative lesions, major unmet medical challenges.
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DOI:
10.3389/fimmu.2016.00658
发表时间:
2016
期刊:
Frontiers in immunology
影响因子:
7.3
作者:
[Butler JA, Cosgrove J, Alden K, Timmis J, Coles MC]
通讯作者:
Coles MC
DOI:
10.3389/fimmu.2021.703088
发表时间:
2021
期刊:
Frontiers in immunology
影响因子:
7.3
作者:
[Cosgrove J, Alden K, Stein JV, Coles MC, Timmis J]
通讯作者:
Timmis J
DOI:
10.1002/psp4.12018
发表时间:
2015-11
期刊:
CPT: pharmacometrics & systems pharmacology
影响因子:
--
作者:
[Cosgrove J, Butler J, Alden K, Read M, Kumar V, Cucurull-Sanchez L, Timmis J, Coles M]
通讯作者:
Coles M
DOI:
10.4049/jimmunol.1402584
发表时间:
2015-11-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
作者:
[Hoorweg K, Narang P, Li Z, Thuery A, Papazian N, Withers DR, Coles MC, Cupedo T]
通讯作者:
Cupedo T
DOI:
10.1084/jem.20150318
发表时间:
2015-10-19
期刊:
The Journal of experimental medicine
影响因子:
--
作者:
[Aparicio-Domingo P, Romera-Hernandez M, Karrich JJ, Cornelissen F, Papazian N, Lindenbergh-Kortleve DJ, Butler JA, Boon L, Coles MC, Samsom JN, Cupedo T]
通讯作者:
Cupedo T
Biophysics of Infection and Immunity: From Molecules to Cells to Tissues
-
批准号:MC_PC_15073
-
项目类别:Intramural
-
资助金额:$86.62万
-
财政年份:2016
-
负责人:Mark Coles
-
依托单位:
Human and Mouse Artificial Lymph Nodes: Novel technology to Reduce and Replace the use of animal models in clinical and developmental immunology
-
批准号:NC/K000527/1
-
项目类别:Research Grant
-
资助金额:$53.39万
-
财政年份:2012
-
负责人:Mark Coles
-
依托单位:
BBSRC Industrial CASE Partnership Grant
-
批准号:BB/I53277X/1
-
项目类别:Training Grant
-
资助金额:$9.59万
-
财政年份:2010
-
负责人:Mark Coles
-
依托单位:
The role of IL-7/IL7R interactions in the development, maintenance and organization of the lymph node microenvironment.
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批准号:G0601156/1
-
项目类别:Research Grant
-
资助金额:$50.44万
-
财政年份:2007
-
负责人:Mark Coles
-
依托单位:
国内基金
海外基金
Innate-likeB细胞受损介导凋亡细胞的清除障碍在系统性红斑狼疮发病中的作用及机制研究
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批准号:81860295
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项目类别:地区科学基金项目
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资助金额:35.0万元
-
批准年份:2018
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负责人:张伟
-
依托单位: