Adaptive Immune Regulation of Traumatic Injury

项目总结 创伤会破坏免疫系统的动态平衡，这会使患者容易患上机会主义。 感染和其他创伤相关并发症，如全身炎症反应综合征(SIRS)， 器官损伤和慢性危重疾病。创伤诱导独特而复杂的宿主反应 由组织损伤和与危险相关的分子模式(DAMP)的释放引发 特定的免疫反应。我们发现了一种称为调节性T细胞(Tregs)的CD4+T细胞亚群 在小鼠烧伤创伤模型中被损伤急性激活。丹参的抗炎抑制活性 Tregs因创伤而增强，这表明Tregs可能控制创伤后炎症的强度 和恢复免疫系统的动态平衡。人的组织中可能含有不同数量的Tregs或 对创伤有不同的功能Treg反应，这可能决定他们对创伤的反应轨迹 创伤性损伤。我们的假设是，树突状细胞控制对湿气的免疫反应，并影响 宿主对创伤的反应轨迹。为了解决这一假设，我们提出了一系列创伤 系统询问的免疫学研究：1)免疫系统表型的Treg调控和 动态平衡；2)创伤诱导的Treg激活机制；3)调节Treg对免疫的影响 表型、抗微生物免疫功能和两次SIRS反应。这个项目的具体目标是 1)确定CD4+Tregs如何控制免疫系统对创伤的反应性；2)确定其特异性 以及创伤反应性CD4+Tregs和其他T细胞的分子性质，3)研究CD4+Tregs如何 影响抗微生物免疫和两次SIRS。我们预计，这项研究的结果将 显著提高我们对调节创伤的特定免疫机制的基础知识 豁免权。我们有几个重要的目标，我们希望在这个项目的过程中实现；1) 对Treg激活和功能的生物学提供新的见解，2)加深对 免疫系统对哺乳动物创伤反应的调控，以及3)探索其治疗潜力 调节Treg的激活和功能作为一种特异性创伤免疫疗法来改善免疫功能和 创伤后的平衡。

PROJECT SUMMARY Traumatic injuries disrupt immune system homeostasis, which can predispose patients to opportunistic infections and other trauma-associated complications like systemic inflammatory response syndrome (SIRS), organ damage, and chronic critical illnesses. Trauma induces unique and complex host responses that are initiated by tissue damage and the release of danger-associated molecular patterns (DAMPs) that trigger specific immune reactions. We identified that a subset of CD4+ T cells called regulatory T cells (Tregs) are acutely activated by injury in a mouse burn trauma model. The counter-inflammatory suppressive activity of Tregs is enhanced by trauma, which suggests that Tregs may control the intensity of post-trauma inflammation and restoration of immune system homeostasis. People can have different numbers of Tregs in their tissues or have different functional Treg responses to trauma that could determine trajectory of their response to traumatic injuries. Our hypothesis is that Tregs control immune reactions to DAMPs and influence the trajectory of the host response to trauma. To address this hypothesis, we propose a series of trauma immunology studies to systematically interrogate; 1) Treg control of immune system phenotypes and homeostasis, 2) trauma-induced Treg activation mechanisms, and 3) effects of modulating Tregs on immune phenotypes, anti-microbial immune function, and the two-hit SIRS response. The specific aims for this project are; 1) To determine how CD4+ Tregs control immune system reactivity to trauma, 2) To define the specificity and molecular nature of trauma-reactive CD4+ Tregs and other T cells, 3) To investigate how CD4+ Tregs influence anti-microbial immunity and two-hit SIRS. We anticipate that the outcome of this research will significantly advance our fundamental knowledge of specific immune mechanisms that modulate trauma immunity. We have several significant goals that we wish to achieve during the course of this project; 1) to provide new insights into the biology of Treg activation and function, 2) to develop a deeper understanding of immune system control of the mammalian trauma response, and 3) to explore the therapeutic potential of modulating Treg activation and function as a specific trauma immunotherapy to improve immune function and balance following trauma.