Foxp3-transduced polyclonal regulatory T cells protect against chronic renal injury from adriamycin
Foxp3-transduced polyclonal regulatory T cells protect against chronic renal injury from adriamycin
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DOI：
10.1681/asn.2005090978
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发表时间：
2006-03-01
影响因子：
13.6
通讯作者：
Alexander, Stephen I.
中科院分区：
文献类型：
--
作者：
Wang, Yuan Min;Zhang, Geoff Yu;Alexander, Stephen I.
慢性蛋白尿性肾损伤是终末期肾病的主要原因。阿霉素肾病是一种慢性蛋白尿性肾病的鼠模型，其中化学损伤之后是模拟人类疾病的免疫和结构变化。Foxp3是诱导调节性T细胞（Treg）表型的基因。假设Foxp3转导的Treg可以保护阿霉素肾病中的肾损伤。用含Foxp3的逆转录病毒或对照逆转录病毒转导CD4+ T细胞。通过功能和表型测定，Foxp3转导的T细胞具有调节表型。Foxp3转导的T细胞的连续转移保护肾损伤。尿蛋白排泄量和血肌酐明显减少（P < 0.05），肾小球硬化、肾小管损害和间质浸润明显减少（P < 0.01）。结论是Foxp3转导的Treg细胞可能在保护慢性蛋白尿肾病免受免疫损伤和疾病进展方面具有治疗作用。
Chronic proteinuric renal injury is a major cause of ESRD. Adriamycin nephropathy is a murine model of chronic proteinuric renal disease whereby chemical injury is followed by immune and structural changes that mimic human disease. Foxp3 is a gene that induces a regulatory T cell (Treg) phenotype. It was hypothesized that Foxp3-transduced Treg could protect against renal injury in Adriamycin nephropathy. CD4+ T cells were transduced with either a Foxp3-containing retrovirus or a control retrovirus. Foxp3-transduced T cells had a regulatory phenotype by functional and phenotypic assays. Adoptive transfer of Foxp3-transduced T cells protected against renal injury. Urinary protein excretion and serum creatinine were reduced (P < 0.05), and there was significantly less glomerulosclerosis, tubular damage, and interstitial infiltrates (P < 0.01). It is concluded that Foxp3-transduced Treg cells may have a therapeutic role in protecting against immune injury and disease progression in chronic proteinuric renal disease.