Function of chemokine receptors in T cell-mediated glomerulonephritis

在人类和实验性新月体肾炎中，CD4+T细胞向肾脏的渗透是一个典型的发现。我们和其他人已经证明，Th1和Th17细胞介导的免疫反应尤其有助于肾组织损伤，而Tregs可能具有有益的特性。肾脏T细胞亚群转运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关键作用。在下一个资助期，我们希望解决以下几点：1.新月体肾炎小鼠模型中CD4+T细胞亚群趋化因子受体表达谱的特征及其在T细胞转运和连续性肾损害中的作用，特别关注CXCR3的白细胞亚群特异性功能。2.阐明肾脏Th17/IL-17免疫反应与趋化因子系统的相互作用。3.建立以荧光为基础的活体显微技术，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.分析肾小球肾炎患者血和肾活检组织中靶分子的表达模式。总之，我们的研究将有助于更好地了解趋化因子/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。这可能有助于靶向性治疗人类T细胞介导的肾小球肾炎。

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.