Elucidating the Cellular and Molecular Mechanisms of How Regulatory T cells in Skin Regulate Fibroblast Activation and Tissue Fibrosis

项目摘要/摘要 调节性T细胞(Tregs)在建立和维持免疫动态平衡方面起着重要作用。然而，一个新兴的 大量研究表明，除了免疫调节功能外，这些细胞在组织中还具有特殊的功能。 细胞。我们发现，皮肤中的Treg在调节成纤维细胞激活和真皮纤维化中发挥着关键作用。 老鼠和人性化的老鼠模型。此外，我们还产生了一种新的蛋白质，可以选择性地激活Tregs 在活体内。这项提议的基本主题是从功能上剖析占主导地位的细胞和分子 皮肤中Tregs影响成纤维细胞功能的机制。我们还将辨别体内的激活 Tregs的作用是减少皮肤纤维化。这里概述的实验在概念和技术上代表了一种 创新的、系统的方法，以更好地了解Treg如何影响皮肤成纤维细胞的生物学。为了做到这一点，我们 将揭示两个皮肤驻留细胞群之间的关键机制联系，对 组织功能。我们的结果可能对伤口愈合和/或慢性纤维性疾病有直接影响， 为这些疾病发现新的治疗策略的可能性。

Project Summary/Abstract Regulatory T cells (Tregs) play a major role in establishing and maintaining immune homeostasis. However, an emerging body of work suggests that these cells have `specialized' functions in tissues in addition to their role as immune regulatory cells. We have discovered that Tregs in skin play a critical role in regulating fibroblast activation and dermal fibrosis in both mouse and humanized mouse models. In addition, we have generated a novel protein that selectively activates Tregs in vivo. The underlying theme of this proposal is to functionally dissect the dominant cellular and molecular mechanisms utilized by Tregs in skin to influence fibroblast function. We will also discern whether in vivo activation of Tregs results in a diminution of skin fibrosis. The experiments outlined herein represent a conceptually and technically innovative, systematic approach to better understand how Tregs influence the biology of skin fibroblasts. In doing so, we will undercover a critical mechanistic link between two skin-resident cell populations with clear and evident impact on tissue function. Our results may have direct implications for wound healing and/or chronic fibrosing diseases, with the possibility of uncovering a new therapeutic strategy for these conditions.