Interleukin-22 in kidney regeneration

IL-22 在肾脏再生中的作用

• 批准号: 252090668
• 负责人: Professor Dr. Hans-Joachim Anders
• 金额: --
• 依托单位: Medizinische Klinik und Poliklinik IV
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/252090668?language=en
• 关键词: Interleukin; 22; kidney; regeneration

The capacity to regenerate renal tissue determines outcomes of acute kidney injury (AK) and chronic kidney disease (CKD). Recent data document that intrarenal mononuclear phagocytes (diverse dendritic cell and macrophage phenotypes) not only drive kidney injury but also kidney regeneration but the associated pro-regeneratory mediators remain unknown. Using a newly developed screening system we identified the recently discovered interleukin IL-22 as such a potential mediator. Our project-specific preliminary data demonstrate that dying tubular epithelial cells release TLR4 agonistic components that stimulate renal dendritic cells to secrete IL-22. IL-22 accelerates the regeneration of of injured tubular cells via IL-22R-mediated MAPK and Erk signaling. Currently, there are no published data on IL-22 and the kidney. In this project we plan to study this previously unknown mechanism of kidney regeneration. We plan to: 1. Study the expression of IL-22 and IL-22R in the following animal models: post-ischemic AKI followed bei either full recovery (AKI) or by progressive tubular atrophy and fibrosis (CKD), aristolochic acid-induced AKI/CKD, and renal fibrosis upon unilateral ureteral obstruction. 2. To study the regulation of IL-22 induction including the effect of TLR agonists, Ahr agonists, and Notch agonists. 3. Characterizing the IL-22-mediated regeneration of tubular epithelial cells, tubular progenitor cells, renal endothelial cells, and renal fibroblasts in vitro. In addition we will study this aspect in vivo using IL-22-deficient mice, IL-22 neutralizing antibodies, depletion of IL-22-producing immune cell subsets, and reconstitution with recombinant IL-22. 4. Finally, we will evaluate the therapeutic potential of recombinant IL-22 on the aforementioned mouse models of kidney injury. We expect that data from this project will overt a previously unknown mechanism of kidney regeneration. Most importantly, this mechanism holds the potential for therapeutic applications, e.g. to accelerate AKI recovery and to slow down the progression of CKD with recombinant IL-22 or other IL-22R agonists.

再生肾脏组织的能力决定了急性肾脏损伤（AK）和慢性肾脏疾病（CKD）的结果。最近的数据文献表明，培育内单核吞噬细胞（不同的树突状细胞和巨噬细胞表型）不仅会驱动肾脏损伤，而且会驱动肾脏再生，而且还造成了相关的促培养基介质。使用新开发的筛查系统，我们将最近发现的白介素IL-22确定为潜在的介体。我们的项目特异性初步数据表明，垂死的管状上皮细胞释放TLR4激动成分，可刺激肾脏树突状细胞分泌IL-22。 IL-22通过IL-22R介导的MAPK和ERK信号传导加速了受伤的管状细胞的再生。目前，尚无有关IL-22和肾脏的发布数据。在这个项目中，我们计划研究这种以前未知的肾脏再生机制。我们计划：1。在以下动物模型中研究IL-22和IL-22R的表达：缺血后AKI随后是BEI完全恢复（AKI）或进行性肾小管萎缩和纤维化（CKD），Aristolochicaid诱导的AKI/CKD和单侧输尿管障碍物时的肾纤维化。 2。研究IL-22诱导的调节，包括TLR激动剂，AHR激动剂和Notch激动剂的作用。 3。表征IL-22介导的肾小管上皮细胞，管状祖细胞，肾脏内皮细胞和肾成纤维细胞体外的再生。此外，我们将使用IL-22缺陷型小鼠，IL-22中和抗体，产生IL-22产生的免疫细胞亚群的耗竭以及重组IL-22重新构成的体内研究这一方面。 4。最后，我们将评估上述肾损伤小鼠模型中重组IL-22的治疗潜力。我们预计该项目的数据将公开以前未知的肾脏再生机制。最重要的是，这种机制具有治疗应用的潜力，例如为了加速AKI恢复并使用重组IL-22或其他IL-22R激动剂来降低CKD的进展。

项目成果

Necroptosis in Acute Kidney Injury

• DOI: 10.1159/000489940
• 发表时间: 2018-01-01
• 期刊: NEPHRON
• 影响因子: 2.5
• 作者: Anders, Hans-Joachim

Evolutionary trade-offs in kidney injury and repair.

• DOI: 10.14670/hh-11-900
• 发表时间: 2017
• 期刊: Histology and histopathology
• 影响因子: 2
• 作者: Y. Lei;H. Anders

Interleukin-22 in kidney injury and regeneration.

• DOI: 10.1152/ajprenal.00005.2015
• 发表时间: 2015-05
• 期刊: American journal of physiology. Renal physiology
• 作者: M. Weidenbusch;Severin Rodler;H. Anders

Gene expression profiling of the Notch-AhR-IL22 axis at homeostasis and in response to tissue injury

• DOI: 10.1042/bsr20170099
• 发表时间: 2017-10
• 期刊: Bioscience Reports
• 影响因子: 4
• 作者: M. Weidenbusch;Severin Rodler;Shangqing Song;S. Romoli;J. Marschner;Franziska Kraft;A. Holderied

Thrombospondin immune regulation and the kidney

• DOI: 10.1093/ndt/gfw431
• 发表时间: 2017-07-01
• 期刊: NEPHROLOGY DIALYSIS TRANSPLANTATION
• 影响因子: 6.1
• 作者: Ponticelli, Claudio;Anders, Hans-Joachim
• 通讯作者: Anders, Hans-Joachim