Pivotal role of CD4+ T cells in renal fibrosis following ureteric obstruction
Pivotal role of CD4+ T cells in renal fibrosis following ureteric obstruction
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DOI：
10.1038/ki.2010.177
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发表时间：
2010-08-01
影响因子：
19.6
通讯作者：
Wong, Wilson
中科院分区：
文献类型：
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作者：
Tapmeier, Thomas T.;Fearn, Amy;Wong, Wilson
肾小管间质纤维化是导致终末期肾衰竭的多种肾脏疾病的常见后果。纤维化程度与白细胞浸润有关。在这里，我们在特征明确的单侧输尿管梗阻小鼠模型中确定了不同 T 细胞群对肾纤维化的作用。用单克隆抗体清除野生型小鼠中的 CD4(+) T 细胞可显着减少梗阻 2 周后的间质扩张量和胶原沉积量。在输尿管梗阻之前，用纯化的CD4(+)而非CD8(+) T细胞重建淋巴细胞减少的RAG敲除小鼠，导致间质扩张和胶原沉积显着增加。输尿管梗阻后，与淋巴细胞减少的 RAG(-/-) 小鼠相比，野生型小鼠的间质扩张和胶原蛋白沉积显着增加；然而，所有组中的巨噬细胞浸润是相同的。因此，我们的结果表明，肾损伤及其随后的纤维化可能是一个多因素的过程，不同阶段涉及免疫系统的不同部分。在这个输尿管梗阻模型中，我们发现CD4(+) T细胞在肾纤维化中发挥着关键作用。这些细胞可能是治疗干预的潜在目标，以防止肾损伤导致的过度纤维化和功能丧失。肾脏国际 (2010) 78, 351-362; doi:10.1038/ki.2010.177；2010 年 6 月 16 日在线发布
Tubulointerstitial fibrosis is a common consequence of a diverse range of kidney diseases that lead to end-stage renal failure. The degree of fibrosis is related to leukocyte infiltration. Here, we determined the role of different T cell populations on renal fibrosis in the well-characterized mouse model of unilateral ureteric obstruction. Depletion of CD4(+) T cells in wild-type mice with a monoclonal antibody significantly reduced the amount of interstitial expansion and collagen deposition after 2 weeks of obstruction. Reconstitution of lymphopenic RAG knockout mice with purified CD4(+) but not CD8(+) T cells, prior to ureteric obstruction, resulted in a significant increase in interstitial expansion and collagen deposition. Wild-type mice had significantly greater interstitial expansion and collagen deposition compared with lymphopenic RAG(-/-) mice, following ureteric obstruction; however, macrophage infiltration was equivalent in all groups. Thus, our results suggest that renal injury with subsequent fibrosis is likely to be a multifactorial process, with different arms of the immune system involved at different stages. In this ureteric obstruction model, we found a critical role for CD4(+) T cells in kidney fibrosis. These cells could be a potential target of therapeutic intervention to prevent excessive fibrosis and loss of function due to renal injury. Kidney International (2010) 78, 351-362; doi:10.1038/ki.2010.177;published online 16 June 2010