Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, PR China.
Ren Fail. 2011;33(10):1025-31. doi: 10.3109/0886022X.2011.618924.
T helper 1 (Th1)/T helper 2 (Th2) profile is pivotal in the development of fibrosis. Renal interstitial fibroblasts, which play a central role in the development of renal interstitial fibrosis, have an intimate relation with lymphocytes. However, there is little knowledge of the effect of fibroblasts on the profile of CD4 T-lymphocyte subsets.
After coculture with rat renal interstitial fibroblasts, the proportions of Th1 and Th2 cells in CD4 T lymphocytes and the apoptosis rates of the two subsets were detected by flow cytometry. Galectin-9 expression in rat renal interstitial fibroblasts was detected by immunofluorescence, Western blotting, and enzyme-linked immunosorbent assay.
After 48 h of coculture, rat renal interstitial fibroblasts increased the proportion of Th2 cells, lowering the ratio of Th1/Th2. Meanwhile, interferon-gamma production in Th1 cells was inhibited and interleukin-4 production in Th2 was promoted. After coculture with activated rat renal interstitial fibroblasts for 24 h, apoptosis of Th1 was more highly promoted than that of Th2 cells. In addition, rat renal interstitial fibroblasts induced stronger Th2 cell differentiation than that of Th1 cells in vitro. Rat renal interstitial fibroblasts expressed but did not secrete galectin-9 (an apoptosis-inducing factor for Th1 cells) in vitro and the expression level decreased when cocultured with CD4 T lymphocytes.
Rat renal interstitial fibroblasts shift the Th1/Th2 profile in vitro, and this may be another pathway by which renal interstitial fibroblasts promote fibrosis.
辅助性 T 细胞 1(Th1)/辅助性 T 细胞 2(Th2)表型在纤维化的发展中起着关键作用。肾间质成纤维细胞在肾间质纤维化的发展中起着核心作用,与淋巴细胞密切相关。然而,对于成纤维细胞对 CD4 T 淋巴细胞亚群表型的影响知之甚少。
将大鼠肾间质成纤维细胞与 CD4 T 淋巴细胞共培养后,通过流式细胞术检测 Th1 和 Th2 细胞在 CD4 T 淋巴细胞中的比例以及两个亚群的凋亡率。通过免疫荧光、Western blot 和酶联免疫吸附试验检测大鼠肾间质成纤维细胞中半乳糖凝集素-9 的表达。
共培养 48 小时后,大鼠肾间质成纤维细胞增加了 Th2 细胞的比例,降低了 Th1/Th2 的比值。同时,抑制了 Th1 细胞中干扰素-γ的产生,促进了 Th2 细胞中白细胞介素-4 的产生。与激活的大鼠肾间质成纤维细胞共培养 24 小时后,Th1 细胞的凋亡更明显。此外,大鼠肾间质成纤维细胞在体外诱导的 Th2 细胞分化强于 Th1 细胞。大鼠肾间质成纤维细胞在体外表达但不分泌半乳糖凝集素-9(一种诱导 Th1 细胞凋亡的因子),与 CD4 T 淋巴细胞共培养时表达水平降低。
大鼠肾间质成纤维细胞在体外改变 Th1/Th2 表型,这可能是肾间质成纤维细胞促进纤维化的另一种途径。