LMU Klinikum, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität Munich, 80336 München, Germany.
Klinikum rechts der Isar, Department of Nephrology, Technical University Munich, 81675 München, Germany.
Int J Mol Sci. 2020 Sep 23;21(19):6978. doi: 10.3390/ijms21196978.
Growth differentiation factor 15 (GDF15) is a member of the transforming growth factor-β (TGF-β) cytokine family and an inflammation-associated protein. Here, we investigated the role of GDF15 in murine anti-glomerular basement membrane (GBM) glomerulonephritis. Glomerulonephritis induction in mice induced systemic expression of GDF15. Moreover, we demonstrate the protective effects for GDF15, as GDF15-deficient mice exhibited increased proteinuria with an aggravated crescent formation and mesangial expansion in anti-GBM nephritis. Herein, GDF15 was required for the regulation of T-cell chemotactic chemokines in the kidney. In addition, we found the upregulation of the CXCR3 receptor in activated T-cells in GDF15-deficient mice. These data indicate that CXCL10/CXCR3-dependent-signaling promotes the infiltration of T cells into the organ during acute inflammation controlled by GDF15. Together, these results reveal a novel mechanism limiting the migration of lymphocytes to the site of inflammation during glomerulonephritis.
生长分化因子 15（GDF15）是转化生长因子-β（TGF-β）细胞因子家族的成员，也是一种与炎症相关的蛋白。在这里，我们研究了 GDF15 在小鼠抗肾小球基底膜（GBM）肾小球肾炎中的作用。肾小球肾炎诱导小鼠系统表达 GDF15。此外，我们证明了 GDF15 的保护作用，因为 GDF15 缺陷小鼠在抗 GBM 肾炎中表现出蛋白尿增加、新月体形成加重和系膜扩张。在此，GDF15 是调节肾脏中 T 细胞趋化趋化因子所必需的。此外，我们发现 GDF15 缺陷小鼠中活化 T 细胞的 CXCR3 受体上调。这些数据表明，CXCL10/CXCR3 依赖性信号促进了 T 细胞在急性炎症期间浸润到器官中，而急性炎症受 GDF15 控制。总之，这些结果揭示了一种新的机制，该机制限制了淋巴细胞在肾小球肾炎期间迁移到炎症部位。
