CD4+T Lymphocytes, Especially Th2 Cells, Contribute to the Progress of Renal Fibrosis
CD4+T Lymphocytes, Especially Th2 Cells, Contribute to the Progress of Renal Fibrosis
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CD4 T 淋巴细胞，尤其是 Th2 细胞，有助于肾纤维化的进展
DOI：
10.1159/000343283
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发表时间：
2012-01-01
影响因子：
4.2
通讯作者：
Chen, Sheng
中科院分区：
文献类型：
--
作者：
Liu, Lili;Kou, Pei;Chen, Sheng
背景：肾小管间质纤维化是肾衰竭的最后常见阶段。损伤后CD 4 + T淋巴细胞的募集和活化可能是介导肾纤维化发生的重要早期事件。但CD 4 + T淋巴细胞在肾纤维化中的作用还存在争议，其细胞机制有待进一步研究。方法：活检标本来自微小病变或伊加肾病患者。采用单侧输尿管梗阻（UUO）诱导小鼠肾纤维化。用抗CD 4抗体耗竭野生型BALB/c小鼠的CD 4 + T淋巴细胞。BALB/c Nu/Nu小鼠通过尾静脉注射用极化的Th 1或Th 2细胞重建。结果：纤维化患者肾脏内有大量CD 4 + T淋巴细胞浸润。CD 4 + T淋巴细胞的耗竭抑制UUO诱导的小鼠肾纤维化。在UUO诱导的肾纤维化过程中，Th 2/Th 1比值随时间延长而升高。Th 2重建小鼠较Th 1重建小鼠更易发生肾纤维化，表现为肾间质扩张和胶原沉积，α-SMA和波形蛋白表达增加，纤维连接蛋白、TGF-β和I型胶原表达增加。我们还发现来自Th 1重建小鼠的CD 4 + T细胞倾向于分泌IL-4和IL-13 Th 2样细胞因子。结论：总之，我们的研究表明，CD 4 + T淋巴细胞在肾纤维化的重要性，并给出了第一个直接的证据，Th 2细胞在UUO诱导的肾纤维化中发挥关键作用。抑制CD 4 + T淋巴细胞向Th 2分化将是预防肾纤维化的潜在治疗干预措施。
Background: Renal tubulointerstitial fibrosis is the final common stage of renal failure. CD4+ T lymphocyte recruitment and activation after injury could be the very important early event that mediates the onset of renal fibrogenesis. But the role of CD4+ T lymphocytes in renal fibrosis is controversial and its cellular mechanism needs to be further investigated. Methods: Biopsy specimens were from patients with minimal-change or IgA nephropathy. Mouse renal fibrosis was induced by unilateral ureteral obstruction (UUO). CD4+ T lymphocytes of wild BALB/c mice were depleted with anti-CD4 antibody. BALB/c Nu/Nu mice were reconstituted with polarized Th1 or Th2 cells by tail vein injection. Results: Our study demonstrated that massive CD4+ T lymphocytes infiltrated fibrotic kidneys of patients. The depletion of CD4+ T lymphocytes inhibited UUO-induced mouse renal fibrosis. In the process of UUO-induced renal fibrosis, the ratios of Th2/Th1 increased with time. Results have also shown that Th2-reconstituted mice developed renal fibrosis more easily than Th1-reconstituted mice, which manifested by interstitial expansion and collagen deposition, higher expression of α-SMA and vimentin and increased expression of fibronectin, TGF-β and collagen I. We also found that CD4+ T cells from Th1-reconstitued mice tended to secrete IL-4 and IL-13 Th2-like cytokines. Conclusion: In conclusion, our study demonstrated the importance of CD4+ T lymphocytes in renal fibrosis and gave the first direct evidence that Th2 cells play a pivotal role in UUO-induced renal fibrosis. Inhibition of CD4+ T lymphocyte differentiation to Th2 would be a potential therapeutic intervention to prevent renal fibrosis.