Galectin-9 ameliorates anti-GBM glomerulonephritis by inhibiting Th1 and Th17 immune responses in mice.
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.
Division of Nephrology, Dept. of Internal Medicine, Tongji Hospital, Huazhong Univ. of Science and Technology, 1095 Jiefang Ave., Wuhan 430030, Hubei, People's Republic of China. jin.yuan@tufts.edu.
Qian
Q
Zhang
Hong
H
Luan
Le
L
Wang
Fan
F
He
Huan
H
Zhou
Xiaoli
X
Xu
Xingai
X
Li
Qing
Q
Xu
Toshiro
T
Niki
Mitsuomi
M
Hirashima
Gang
G
Xu
Yongman
Y
Lv
Jin
J
Yuan
D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000276:immunology / Q000517:prevention & control*; D001323:Autoantibodies / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D037161:Galectins / Q000494:pharmacology*; D000072597:Hepatitis A Virus Cellular Receptor 2; D007668:Kidney / Q000276:immunology; D051379:Mice; D011991:Receptors, Virus / Q000096:biosynthesis; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology*; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology*
D001323:Autoantibodies; D037161:Galectins; C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D011991:Receptors, Virus; C051951:antiglomerular basement membrane antibody; C508186:galectin 9, mouse
Th17 cells; Th2 cells; Tim-3; anti-GBM glomerulonephritis; galectin-9