RORgamma+ Innate Lymphoid Cells in Skin Wound Healing

RORgamma 先天淋巴细胞在皮肤伤口愈合中的作用

• 批准号: MR/K021125/1
• 负责人: Mark Coles
• 金额: $ 53.4万
• 依托单位: University of York
• 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
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FK021125%2F1
• 关键词: RORgamma+; Innate; Lymphoid; Cells; Skin

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.

正常的伤口愈合在身体内持续发生，对维持正常的健康和健身具有关键作用。最近，在肠道中发现了一种特殊类型的免疫细胞，称为先天淋巴样细胞，它在维持正常肠道功能方面起着关键作用。我们已经发现，这些细胞可以传播到皮肤，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，即T淋巴细胞在伤口中诱导形成疤痕样组织来实现的。当正常愈合不能正常发生时，会导致疼痛和难以治疗的病理现象，因此需要更好地了解正常伤口愈合的过程。在这项研究中，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调节的，从而使伤口快速愈合而不会留下毁容。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。我们将分析不同细胞如何相互通信，以及这些信号的时序如何控制正常的愈合过程。我们将研究这一过程如何被感染伤口的机会性细菌的存在所调节，以及这如何改变伤口愈合过程。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准备摧毁入侵细菌和病毒的士兵大军。我们的初步数据表明，免疫细胞的一部分应该被视为“治疗者”而不是“士兵”，在维持正常伤口愈合方面具有特殊的作用。通过了解免疫细胞如何控制皮肤屏障的功能和修复，将有助于开发治疗炎症性皮肤疾病和溃疡性病变的新疗法，这些都是尚未得到满足的主要医学挑战。

项目成果

Model-Driven Experimentation: A New Approach to Understand Mechanisms of Tertiary Lymphoid Tissue Formation, Function, and Therapeutic Resolution.

• 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

Simulating CXCR5 Dynamics in Complex Tissue Microenvironments.

• 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

Agent-Based Modeling in Systems Pharmacology.

• DOI: 10.1002/psp4.12018
• 发表时间: 2015-11
• 期刊: CPT: pharmacometrics & systems pharmacology
• 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

A Stromal Cell Niche for Human and Mouse Type 3 Innate Lymphoid Cells.

• DOI: 10.4049/jimmunol.1402584
• 发表时间: 2015-11-01
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Hoorweg K;Narang P;Li Z;Thuery A;Papazian N;Withers DR;Coles MC;Cupedo T
• 通讯作者: Cupedo T

Type 3 innate lymphoid cells maintain intestinal epithelial stem cells after tissue damage.

• DOI: 10.1084/jem.20150318
• 发表时间: 2015-10-19
• 期刊: The Journal of experimental medicine
• 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