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

被引：41

作者：

Zhang, Qian ^{[1
]}

Luan, Hong ^{[1
]}

Wang, Le ^{[1
]}

He, Fan ^{[1
]}

Zhou, Huan ^{[1
]}

Xu, Xiaoli ^{[1
]}

Li, Xingai ^{[1
]}

Xu, Qing ^{[1
]}

Niki, Toshiro ^{[2
,3
]}

Hirashima, Mitsuomi ^{[2
,3
]}

Xu, Gang ^{[1
]}

Lv, Yongman ^{[1
]}

Yuan, Jin ^{[1
,4
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Div Nephrol,Dept Internal Med, Wuhan 430030, Hubei, Peoples R China

[2] GalPharma Co Ltd, Div Res, Takamatsu, Kagawa, Japan

[3] Kagawa Univ, Fac Med, Dept Immunol & Immunopathol, Takamatsu, Kagawa 760, Japan

[4] Tufts Med Ctr, Mol Cardiol Res Inst, Translat Immunol Sci Ctr, Boston, MA USA

来源：

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY | 2014年 / 306卷 / 08期

基金：

美国国家科学基金会;

关键词：

galectin-9; Tim-3; Th17; cells; Th2; anti-GBM glomerulonephritis; REGULATORY T-CELLS; CRESCENTIC GLOMERULONEPHRITIS; RENAL INJURY; TIM-3; CHEMOKINES; INDUCTION; NEPHRITIS; PROLIFERATION; CONTRIBUTES; MACROPHAGES;

D O I：

10.1152/ajprenal.00294.2013

中图分类号：

Q4 [生理学];

学科分类号：

071003 ;

摘要：

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-gamma 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.

引用

页码：F822 / F832

页数：11

共 38 条

[1] CC chemokine ligand 5/RANTES chemokine antagonists aggravate glomerulonephritis despite reduction of glomerular leukocyte infiltration [J].