Galectin-9 ameliorates anti-GBM glomerulonephritis by inhibiting Th1 and Th17 immune responses in mice.
Galectin-9 ameliorates anti-GBM glomerulonephritis by inhibiting Th1 and Th17 immune responses in mice.
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DOI：
10.1152/ajprenal.00294.2013
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发表时间：
2014-04
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影响因子：
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通讯作者：
Qian Zhang;H. Luan;Le Wang;Fan He;Huan Zhou;Xiaoli Xu;Xingai Li;Qing Xu;T. Niki;M. Hirashima;Gang Xu;Yongman Lv;Jin Yuan
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文献类型：
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作者：
Qian Zhang;H. Luan;Le Wang;Fan He;Huan Zhou;Xiaoli Xu;Xingai Li;Qing Xu;T. Niki;M. Hirashima;Gang Xu;Yongman Lv;Jin Yuan
抗肾小球基底膜肾炎（anti-GBM GN）是一种以Th 1和Th 17为主的自身免疫性疾病。半乳糖凝集素-9（Galectin-9，Gal-9）是Tim-3的配体，参与多种生物学过程并导致CD 4（+）Tim-3（+）T细胞凋亡。Gal-9是如何调节Th 1和Th 17细胞的功能并防止抗GBM GN中的肾损伤的，目前尚不清楚。在该研究中，将Gal-9施用于抗GBM GN小鼠7天。我们发现Gal-9可以延缓Scr的升高，减轻肾小管损伤，减少新月体的形成。在Gal-9处理的肾炎小鼠中，Th 1和Th 17细胞向脾和肾中的浸润显著减少。Th 1和Th 17细胞浸润的减少可能与肾脏中CCL-20、CXCL-9和CXCL-10 mRNA的下调有关。平行地，在第21天和第28天，在Gal-9处理的肾炎小鼠中IFN-γ和IL-17 A的血液水平下降。此外，在注射Gal-9 7天后，在肾炎小鼠的肾脏中观察到增强的Th 2细胞介导的免疫应答。总之，Gal-9在抗GBM GN中的保护作用与抑制Th 1和Th 17细胞介导的免疫应答以及增强肾脏中的Th 2免疫有关。
Antiglomerular basement membrane glomerulonephritis (anti-GBM GN) is a Th1- and Th17-predominant autoimmune disease. Galectin-9 (Gal-9), identified as the ligand of Tim-3, functions in diverse biological processes and leads to the apoptosis of CD4(+)Tim-3(+) T cells. It is still unclear how Gal-9 regulates the functions of Th1 and Th17 cells and prevents renal injury in anti-GBM GN. In this study, Gal-9 was administered to anti-GBM GN mice for 7 days. We found that Gal-9 retarded the increase of Scr, ameliorated renal tubular injury, and reduced the formation of crescents. The infiltration of Th1 and Th17 cells into the spleen and kidneys significantly decreased in Gal-9-treated nephritic mice. The reduced infiltration of Th1 and Th17 cells might be associated with the downregulation of CCL-20, CXCL-9, and CXCL-10 mRNAs in the kidney. In parallel, the blood levels of IFN-γ and IL-17A declined in Gal-9-treated nephritic mice at days 21 and 28. In addition, an enhanced Th2 cell-mediated immune response was observed in the kidneys of nephritic mice after a 7-day injection of Gal-9. In conclusion, the protective role of Gal-9 in anti-GBM GN is associated with the inhibition of Th1 and Th17 cell-mediated immune responses and enhanced Th2 immunity in the kidney.