Endogenous Tim-1 (Kim-1) promotes T-cell responses and cell-mediated injury in experimental crescentic glomerulonephritis
Endogenous Tim-1 (Kim-1) promotes T-cell responses and cell-mediated injury in experimental crescentic glomerulonephritis
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DOI：
10.1038/ki.2011.424
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发表时间：
2012-05-01
影响因子：
19.6
通讯作者：
Kitching, A. Richard
中科院分区：
文献类型：
--
作者：
Nozaki, Yuji;Nikolic-Paterson, David J.;Kitching, A. Richard
T细胞免疫球蛋白粘蛋白1（Tim-1）调节CD 4（+）T细胞反应，也由肾脏中受损的近端小管表达，称为肾损伤分子-1（Kim-1）。我们试图确定内源性Tim-1在绵羊抗小鼠肾小球基底膜球蛋白作为外源性抗原诱导的实验性T细胞介导的肾小球肾炎中的作用。在该模型中，Tim-1通过浸润活化的CD 4（+）细胞表达，我们研究了抑制性抗Tim-1抗体（RMT 1 -10）对免疫应答和肾小球疾病的影响。用抗Tim-1抗体治疗后，新月体肾小球肾炎、增殖性损伤和白细胞蓄积减弱，但间质foxp 3（+）细胞蓄积和白细胞介素-10 mRNA增加。免疫系统中的T细胞增殖和凋亡沿着免疫系统和肾脏内Th 1和Th 17细胞应答的选择性减少。抗Tim-1抗体降低了Kim-1的尿排泄和肾脏表达，反映了间质损伤减少。抗Tim-1抗体的作用在肾损伤的早期阶段不明显，此时对羊球蛋白的免疫应答正在发展。因此，内源性Tim-1促进Th 1和Th 17致肾炎免疫应答，其中和作用减少肾损伤，同时限制细胞介导的肾小球肾炎中的炎症。Kidney International（2012）81，844-855; doi：10.1038/ki.2011.424; 2011年12月28日在线发表
The T-cell immunoglobulin mucin 1 (Tim-1) modulates CD4(+) T-cell responses and is also expressed by damaged proximal tubules in the kidney where it is known as kidney injury molecule-1 (Kim-1). We sought to define the role of endogenous Tim-1 in experimental T-cell-mediated glomerulonephritis induced by sheep anti-mouse glomerular basement membrane globulin acting as a planted foreign antigen. Tim-1 is expressed by infiltrating activated CD4(+) cells in this model, and we studied the effects of an inhibitory anti-Tim-1 antibody (RMT1-10) on immune responses and glomerular disease. Crescentic glomerulonephritis, proliferative injury, and leukocyte accumulation were attenuated following treatment with anti-Tim-1 antibodies, but interstitial foxp3(+) cell accumulation and interleukin-10 mRNA were increased. T-cell proliferation and apoptosis decreased in the immune system along with a selective reduction in Th1 and Th17 cellular responses both in the immune system and within the kidney. The urinary excretion and renal expression of Kim-1 was reduced by anti-Tim-1 antibodies reflecting diminished interstitial injury. The effects of anti-Tim-1 antibodies were not apparent in the early phase of renal injury, when the immune response to sheep globulin was developing. Thus, endogenous Tim-1 promotes Th1 and Th17 nephritogenic immune responses and its neutralization reduces renal injury while limiting inflammation in cell-mediated glomerulonephritis. Kidney International (2012) 81, 844-855; doi:10.1038/ki.2011.424; published online 28 December 2011