Galectin-9 ameliorates anti-GBM glomerulonephritis by inhibiting Th1 and Th17 immune responses in mice.

Abstract

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.

• Authors: Qian Zhang, Hong Luan, Le Wang, Fan He, Huan Zhou, Xiaoli Xu, Xingai Li, Qing Xu, Toshiro Niki, Mitsuomi Hirashima, Gang Xu, Yongman Lv, Jin Yuan
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 306 Issue 8 Pg. F822-32 (Apr 15 2014) ISSN: 1522-1466 [Electronic] United States
• PMID: 24477688 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• Galectins
• Havcr2 protein, mouse
• Hepatitis A Virus Cellular Receptor 2
• Receptors, Virus
• antiglomerular basement membrane antibody
• galectin 9, mouse

Topics

• Animals
• Anti-Glomerular Basement Membrane Disease (immunology, prevention & control)
• Autoantibodies (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• Galectins (pharmacology)
• Hepatitis A Virus Cellular Receptor 2
• Kidney (immunology)
• Mice
• Receptors, Virus (biosynthesis)
• Th1 Cells (drug effects, immunology)
• Th17 Cells (drug effects, immunology)