Lei Ling, Zhong Xiao-Ning, He Zhi-Yi, Zhao Cheng, Sun Xue-Jiao
Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Cell Biol Int. 2015 Apr;39(4):388-99. doi: 10.1002/cbin.10410. Epub 2015 Jan 20.
Systemic sclerosis (SSc) is a connective tissue disease characterized by fibrosis of the skin and internal organs. Th17 cells and interleukin-17 (also called IL-17A) have been found to be increased in peripheral blood and skin in patients with SSc. IL-21 is a potent inducer of Th17 differentiation that is produced by activated T cells, and whose relationship with Th17 cells in SSc is unclear. Here, using a bleomycin (BLM)-induced mouse model of skin fibrosis, we detected the frequency of CD4+/IL-17+ (Th17) cells, CD4+/IL-21+ T cells and IL-21+ Th17 cells in peripheral blood, skin and lungs, as well as the serum content of IL-17A and IL-21. In addition, we assessed the differentiation of CD4+ T cells cultured from these mice into Th17 cells in response to treatment with IL-21. Compared with the control mice, Th17 cell counts and IL-17A levels were significantly increased and correlated with inflammatory and fibrotic indices in the skin and lungs of the BLM-induced fibrosis mice. Moreover, serum levels of CD4+/IL-21+ T cells, IL-21+ Th17 cells, and IL-21 were significantly increased in these mice, and correlated positively with serum levels of Th17 cells. In vitro experiments showed that IL-21 treated CD4+ T cells derived from BLM-induced mice differentiated into Th17 cells. Our results indicate that Th17 cells and IL-17A contributes to inflammatory and fibrotic processes in the skin and lungs in a BLM-induced mouse model of SSc. Moreover, the expansion of the Th17 cell population may be subsequent to IL-21 promotion of the differentiation of CD4+ T cells in these mice.
系统性硬化症（SSc）是一种以皮肤和内脏器官纤维化为特征的结缔组织疾病。已发现SSc患者外周血和皮肤中的辅助性T细胞17（Th17细胞）和白细胞介素-17（也称为IL-17A）有所增加。IL-21是由活化T细胞产生的Th17分化的有效诱导剂，其与SSc中Th17细胞的关系尚不清楚。在此，我们使用博来霉素（BLM）诱导的皮肤纤维化小鼠模型，检测外周血、皮肤和肺中CD4+/IL-17+（Th17）细胞、CD4+/IL-21+T细胞和IL-21+Th17细胞的频率，以及IL-17A和IL-21的血清含量。此外，我们评估了从这些小鼠培养的CD4+T细胞在接受IL-21治疗后向Th17细胞的分化情况。与对照小鼠相比，BLM诱导的纤维化小鼠皮肤和肺中的Th17细胞计数和IL-17A水平显著增加，且与炎症和纤维化指标相关。此外，这些小鼠血清中CD4+/IL-21+T细胞、IL-21+Th17细胞和IL-21的水平显著升高，并与Th17细胞的血清水平呈正相关。体外实验表明，IL-21处理来自BLM诱导小鼠的CD4+T细胞可分化为Th17细胞。我们的结果表明，在BLM诱导的SSc小鼠模型中，Th17细胞和IL-17A参与了皮肤和肺中的炎症和纤维化过程。此外，Th17细胞群体的扩增可能是IL-21促进这些小鼠中CD4+T细胞分化的结果。
