Wang Ying, Wang Li-Li, Yang Hao-Yu, Wang Fei-Fei, Zhang Xue-Xiu, Bai Yan-Ping
Clinical Institute of China-Japan Friendship Hospital, Graduate School of Peking Union Medical CollegeBeijing, China; Department of Dermatology & Venerology, China-Japan Friendship HospitalBeijing, China.
Department of Dermatology & Venerology, China-Japan Friendship HospitalBeijing, China; Beijing University of Chinese MedicineBeijing, China.
Am J Transl Res. 2016 Jul 15;8(7):3188-96. eCollection 2016.
Interleukin-21 (IL-21) and T helper 17 (Th17) cells are known to be involved in the pathogenesis of psoriasis, but little is known about their relationship in psoriasis. Herein, we investigated whether IL-21 could regulate Th17 cell induction in patients with psoriasis vulgaris. 32 patients with psoriasis vulgaris and 13 healthy controls were recruited. Flow cytometry was used to detect the frequencies of cells mainly secreting IL-21 (including IL-21+CD4+ T and IL-21+ Th17 cells) and Th17 cells. An enzyme-linked immunosorbent assay (ELISA) was used to determine the serum content of IL-21. Severity of the psoriasis was evaluated by a Psoriasis Area and Severity Index (PASI) score. In addition, the differentiation of CD4+ T cells with IL-21 and the different frequencies of IL-21+CD4+ T cells, IL-21+ Th17 cells and Th17 cells were assessed, as were serum levels of IL-21 in patients with moderate to severe psoriasis before and after treatment. Our results showed that the levels of IL-21, IL-21+CD4+ T cells, IL-21+ Th17 cells and Th17 cells were significantly increased in patients and positively associated with PASI score (P < 0.01). Moreover, the levels of IL-21, IL-21+CD4+ T cells and IL-21+ Th17 cells were positively correlated with the frequency of Th17 cells (P < 0.01). In vitro experiments demonstrated that IL-21 could promote CD4+ T cells to differentiate into Th17 cells. After a 4-week treatment of acitretin and a topical therapy, all the immune markers observed in patients decreased significantly (P < 0.01), but the levels remained higher than those in healthy controls (P < 0.01). These findings indicate that IL-21 might promote Th17 cell induction in psoriasis and might be a potential immune marker for targeting this disease.
已知白细胞介素-21(IL-21)和辅助性T细胞17(Th17)细胞参与银屑病的发病机制,但它们在银屑病中的关系鲜为人知。在此,我们研究了IL-21是否能调节寻常型银屑病患者Th17细胞的诱导。招募了32例寻常型银屑病患者和13名健康对照者。采用流式细胞术检测主要分泌IL-21的细胞(包括IL-21+CD4+T细胞和IL-21+Th17细胞)及Th17细胞的频率。采用酶联免疫吸附测定(ELISA)法测定血清IL-21含量。通过银屑病面积和严重程度指数(PASI)评分评估银屑病的严重程度。此外,评估了IL-21对CD4+T细胞的分化作用以及IL-21+CD4+T细胞、IL-21+Th17细胞和Th17细胞的不同频率,以及中重度银屑病患者治疗前后的血清IL-21水平。我们的结果显示,患者体内IL-21、IL-21+CD4+T细胞、IL-21+Th17细胞和Th17细胞水平显著升高,且与PASI评分呈正相关(P<0.01)。此外,IL-21、IL-21+CD4+T细胞和IL-21+Th17细胞水平与Th17细胞频率呈正相关(P<0.01)。体外实验表明,IL-21可促进CD4+T细胞分化为Th17细胞。经4周阿维A治疗和局部治疗后,患者体内观察到的所有免疫标志物均显著下降(P<0.01),但仍高于健康对照者(P<0.01)。这些发现表明,IL-21可能促进银屑病中Th17细胞的诱导,可能是针对该疾病的潜在免疫标志物。