Characterization and interaction of immunosuppressive cells in burn and sepsis

烧伤和脓毒症中免疫抑制细胞的特征和相互作用

• 批准号: 423969360
• 负责人: Dr. Christian Bergmann
• 金额: --
• 依托单位: Klinik für Unfall-, Hand-, Plastische und Wiederherstellungschirurgie
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/423969360?language=en
• 关键词: Characterization; interaction; immunosuppressive; cells; burn

Persistent Inflammation, Immune Suppression and Catabolism Syndrome (PICS) is a state in which mainly ICU patients fail to regain health after sepsis or trauma. Until today this syndrome is poorly described and can only be treated symptomatically. One of its clinical determinants is prolonged immunosuppression. To gain further understanding of PICS the workgroup of professor Caldwell at the University of Cincinnati developed a murine PICS model. Based on this work I will further characterize the behavior of immunosuppression in burn and sepsis leading to PICS. Relevant immunosuppressive functions are described in Neutrophils, MDSCs, Tregs, Tr1 T cells and DN T cells. These cells are able to secrete the immunosuppressive cytokines IL-10 and TGF-β. Partially knowledge about the interaction between these cells exist. However, this is fragmentary and its relevance concerning the development of prolonged immunosuppression is not well elucidated. In this work I will test the hypothesis that Neutrophils, MDSCs, Tregs, Tr1 T cells and DN T cells contribute significantly to the development of post-traumatic and -septic development of immunosuppression and interact in an IL-10 and TGF-β dependent manner.

持续性炎症、免疫抑制和分解代谢综合征（PICS）是ICU患者在败血症或创伤后无法恢复健康的一种主要状态。直到今天，这种综合征还没有得到很好的描述，只能对症治疗。其临床决定因素之一是长期免疫抑制。为了进一步了解PICS，辛辛那提大学的Caldwell教授的工作组开发了一个小鼠PICS模型。在此基础上，我将进一步描述烧伤和败血症导致PICS的免疫抑制行为。在中性粒细胞、MDSCs、Tregs、Tr1 T细胞和DN T细胞中描述了相关的免疫抑制功能。这些细胞能够分泌免疫抑制因子IL-10和TGF-β。关于这些细胞之间相互作用的部分知识是存在的。然而，这是不完整的，其与长期免疫抑制发展的相关性还没有很好地阐明。在这项工作中，我将检验中性粒细胞、MDSCs、Tregs、Tr1 T细胞和DN T细胞对创伤后和脓毒性免疫抑制的发展有重要贡献的假设，并以IL-10和TGF-β依赖的方式相互作用。

项目成果

TPPU treatment of burned mice dampens inflammation and generation of bioactive DHET which impairs neutrophil function.

• DOI: 10.1038/s41598-021-96014-2
• 发表时间: 2021-08-16
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Bergmann CB;Hammock BD;Wan D;Gogolla F;Goetzman H;Caldwell CC;Supp DM
• 通讯作者: Supp DM

sEH-derived metabolites of linoleic acid drive pathologic inflammation while impairing key innate immune cell function in burn injury.

• DOI: 10.1073/pnas.2120691119
• 发表时间: 2022-03-29
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1