T cell reactivation in acute kidney injury

急性肾损伤中的 T 细胞再激活

基本信息

项目摘要

Lymphocyte effector responses are a hallmark of inflammatory processes. Past studies have identified CD4 T cells to be crucially involved in both ischemia-reperfusion mediated kidney injury and glomerulonephritis. However, reactivation of these cells in the tissue is necessary to elicit their biological function. The aim of this study is to characterize the reactivation process of effector T cells in the tissue in models of acute kidney injury. First, we aim to identify the antigen presenting cell responsible for tissue reactivation (as opposed to dendritic cells that mediate priming). In this context we will use a novel FACS based approach to investigate in vivo cell conjugates following ischemia-reperfusion injury and an established glomerulonephritis model with a known antigen. Furthermore, we will examine the role of CD4 T cells in the development of a clinically relevant sepsis induced kidney injury model. Secondly, the transcriptome of reactivating T cells will be analyzed using RNAseq technology. For this purpose, different characteristics of reactivating T cells will be assessed and correlated to identify reactivated T cells. The results of this transcriptome analysis will then be examined in ischemia-reperfusion injury, sepsis induced kidney injury and glomerulonephritis and, in addition, in their dependency on costimulatory molecules and their association with molecules known to be involved in T cell exhaustion. Thirdly, the importance of myeloid cells for reactivation in the tissue will be examined using antibody depletion studies and knockout mice previously reported to have impaired myeloid cell recruitment but intact T cell recruitment.
淋巴细胞效应反应是炎症过程的标志。过去的研究已经确定CD 4 T细胞在缺血-再灌注介导的肾损伤和肾小球肾炎中起关键作用。然而,这些细胞在组织中的再活化是引发其生物学功能所必需的。本研究的目的是表征急性肾损伤模型中组织中效应T细胞的再活化过程。首先,我们的目标是确定负责组织再活化的抗原呈递细胞(而不是介导引发的树突状细胞)。在这种情况下,我们将使用一种新的基于流式细胞仪的方法来研究在体内的细胞结合物缺血再灌注损伤和一个已知的抗原与已建立的肾小球肾炎模型。此外,我们将研究CD 4 T细胞在临床相关的脓毒症诱导的肾损伤模型的发展中的作用。其次,将使用RNAseq技术分析再活化T细胞的转录组。为此目的,将评估再活化T细胞的不同特征并将其关联以鉴定再活化T细胞。然后将在缺血-再灌注损伤、脓毒症诱导的肾损伤和肾小球肾炎中检查该转录组分析的结果,此外,还检查它们对共刺激分子的依赖性及其与已知参与T细胞耗竭的分子的关联。第三,骨髓细胞在组织中再活化的重要性将使用抗体耗竭研究和先前报道的具有受损的骨髓细胞募集但完整的T细胞募集的敲除小鼠来检查。

项目成果

期刊论文数量(7)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Radiation induced regulation of endothelial adhesion receptors
辐射诱导的内皮粘附受体调节
  • DOI:
    10.1096/fasebj.2020.34.s1.09424
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Kiljan M;Weil S;Vásquez-Torres A;Hettich M;Reinscheid M;Ibruli O;Baues C;Marnitz S;Baus W;Herter-Sprie G;Herter J
  • 通讯作者:
    Herter J
Transcriptome analysis of reactivated TH1 cells reveal distinct differences between priming and reactivation processes
重新激活的 TH1 细胞的转录组分析揭示了启动和重新激活过程之间的明显差异
  • DOI:
    10.1096/fasebj.2021.35.s1.02700
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Kiljan M;Camacho Velázquez O;Ercanoglu M;Hesselmann I;Sahbaz Y;Wagner E;Lackmann JW;Hillmer A;Sorokin L;Engelbertsen D;Klein F;Baues C;Marnitz-Schulze S;Herter-Sprie GS;Herter JM
  • 通讯作者:
    Herter JM
CyberKnife radiation therapy as a platform for translational mouse studies
射波刀放射治疗作为转化小鼠研究的平台
  • DOI:
    10.1080/09553002.2021.1934749
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    2.6
  • 作者:
    Kiljan M;Weil S;Vásquez-Torres A;Hettich M;Mayer M;Ibruli O;Reinscheid M;Heßelmann I;Niu LN;Sahbaz Y;Baues C;Baus WW;Kamp F;Marnitz S;Herter-Sprie GS;Herter JM
  • 通讯作者:
    Herter JM
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Dr. Jan Herter其他文献

Dr. Jan Herter的其他文献

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{{ truncateString('Dr. Jan Herter', 18)}}的其他基金

The role of the cAMP responsive protein AKAP9 in integrin mediated T cell recruitment to the kidney in acute kidney injury
cAMP 反应蛋白 AKAP9 在急性肾损伤中整合素介导的 T 细胞募集到肾脏中的作用
  • 批准号:
    227575761
  • 财政年份:
    2012
  • 资助金额:
    --
  • 项目类别:
    Research Fellowships

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治疗靶向 p53 重新激活诱导的 OXPHOS 依赖性和应激反应,以克服 AML 中对 Venetoclax/HMA 的耐药性
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The role of RNA m6A modification in the regulation of HIV latency and reactivation
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