Function of chemokine receptors in T cell-mediated glomerulonephritis

CD4+ T细胞浸润到肾脏是人类和实验性月牙状肾小球肾炎的典型发现。我们和其他人已经表明，Th1和Th17细胞介导的免疫反应，特别是有助于肾组织损伤，而Tregs可能具有有益的特性。肾T细胞亚群运输和激活的潜在机制尚不完全清楚。然而，趋化因子和趋化因子受体被认为起着至关重要的作用。在下一个资助期内，我们希望解决以下问题：小鼠月牙状肾小球肾炎模型中CD4+ T细胞亚群趋化因子受体表达谱的表征及其在T细胞转运和连续肾损伤中的功能作用，特别关注CXCR3的白细胞亚群特异性功能。2. 澄清肾脏Th17/IL-17免疫反应与趋化因子系统之间的相互作用。3. 建立基于荧光的体内显微镜技术，用于观察肾脏T细胞在稳态和炎症条件下的迁移和相互作用。4. 靶分子在肾小球肾炎患者血液样本及肾活检中的表达模式分析。总之，我们的研究将有助于更好地理解趋化因子/趋化因子受体调节的T细胞运输及其在肾组织损伤中的作用。这可能有助于人类T细胞介导的肾小球肾炎的靶向特异性治疗。

The infiltration of CD4+ T cells into the kidney is a typical finding in human and experimental crescentic glomerulonephritis. We and others have shown that Th1 and Th17 cell-mediated immune responses, in particular, contribute to renal tissue injury, while Tregs could have beneficial properties. The underlying mechanisms of renal T cell subset trafficking and activation are incompletely understood. However, chemokines and chemokine receptors are thought to play a crucial role. In the next funding period, we wish to address the following points: 1. Characterization of the chemokine receptor expression profile of CD4+ T cell subsets and definition of their functional role for T cell trafficking and consecutive kidney damage in a murine model of crescentic glomerulonephritis, with specific focus on the leukocyte subset-specific function of CXCR3. 2. Clarification of the interaction between the renal Th17/IL-17 immune response and the chemokine system. 3. Establishment of fluorescence-based in vivo microscopy techniques for the visualization of renal T cell migration and interaction under homeostatic and inflammatory conditions. 4. Analysis of the expression pattern of target molecules in blood samples and renal biopsies of patients with glomerulonephritis. In summary our studies will result in a better understanding of chemokine/chemokine receptor-regulated T cell trafficking and its role in renal tissue injury. This might facilitate target-specific therapy in human T cell-mediated glomerulonephritis.