Arthritis Res Ther. 2013 Sep 26;15(5):R136. doi: 10.1186/ar4317.
The aim of this study was to characterize interleukin 17 (IL-17) and interleukin 22 (IL-22) producing cells in peripheral blood (PB), skin, synovial fluid (SF) and synovial tissue (ST) in patients with psoriasis (Ps) and psoriatic arthritis (PsA).
Flow cytometry was used to enumerate cells making IL-22 and IL-17, in skin and/or SF and PB from 11 patients with Ps and 12 patients with PsA; skin and PB of 15 healthy controls and SF from rheumatoid arthritis (RA) patients were used as controls. Expression of the interleukin 23 receptor (IL-23R) and chemokine receptors CCR4 and CCR6 was examined. Secretion of IL-17 and IL-22 was measured by ELISA. ST was analysed by immunohistochemical staining of IL-17 and IL-22.
Increased frequencies of IL-17+ and IL-22+ CD4+ T cells were seen in PB of patients with PsA and Ps. IL-17 secretion was significantly elevated in both PsA and Ps, whilst IL-22 secretion was higher in PsA compared to Ps and healthy controls. A higher proportion of the CD4+ cells making IL-17 or IL-22 expressed IL-23R and frequencies of IL-17+, CCR6+ and CCR4+ T cells were elevated in patients with Ps and those with PsA. In patients with PsA, CCR6+ and IL-23R + T cells numbers were elevated in SF compared to PB. Increased frequencies of IL-17+ and IL-22+ CD4+ T cells were demonstrated in Ps skin lesions. In contrast, whilst elevated frequencies of CD4+ IL-17+ cells were seen in PsA SF compared to PB, frequencies of CD4+ IL-22+ T cells were lower. Whereas IL-17 expression was equivalent in PsA, osteoarthritis (OA) and RA ST, IL-22 expression was higher in RA than either OA or PsA ST, in which IL-22 was strikingly absent.
Elevated frequencies of IL-17 and IL-22 producing CD4+ T cells were a feature of both Ps and PsA. However their differing distribution at disease sites, including lower frequencies of IL-22+ CD4+ T cells in SF compared to skin and PB, and lack of IL-22 expression in ST suggests that Th17 and Th22 cells have common, as well as divergent roles in the pathogenesis of Ps and PsA.
本研究的目的是描述白细胞介素 17(IL-17)和白细胞介素 22(IL-22)在银屑病(Ps)和银屑病关节炎(PsA)患者外周血(PB)、皮肤、滑液(SF)和滑膜组织(ST)中的产生细胞。
采用流式细胞术检测 11 例 Ps 患者和 12 例 PsA 患者皮肤和/或 SF 和 PB 中产生 IL-22 和 IL-17 的细胞,15 例健康对照者的皮肤和 PB 及类风湿关节炎(RA)患者的 SF 作为对照。检测白细胞介素 23 受体(IL-23R)和趋化因子受体 CCR4 和 CCR6 的表达。通过 ELISA 测量 IL-17 和 IL-22 的分泌。通过 IL-17 和 IL-22 的免疫组织化学染色分析 ST。
PsA 和 Ps 患者的 PB 中观察到 IL-17+和 IL-22+CD4+T 细胞的频率增加。IL-17 在 PsA 和 Ps 中均显著升高,而 IL-22 在 PsA 中较 Ps 和健康对照者更高。在 Ps 和 PsA 患者中,产生 IL-17 或 IL-22 的 CD4+细胞中更高比例表达 IL-23R,IL-17+、CCR6+和 CCR4+T 细胞的频率升高。与 PB 相比,PsA 患者的 SF 中 CCR6+和 IL-23R+T 细胞数量增加。在 Ps 皮肤病变中观察到 IL-17+和 IL-22+CD4+T 细胞的频率增加。相比之下,尽管 PsA SF 中 CD4+IL-17+细胞的频率高于 PB,但 CD4+IL-22+T 细胞的频率较低。虽然 IL-17 在 PsA、骨关节炎(OA)和 RA ST 中的表达相当,但在 RA 中 IL-22 的表达高于 OA 或 PsA ST,在这些 ST 中 IL-22 明显缺失。
升高的 IL-17 和 IL-22 产生 CD4+T 细胞的频率是 Ps 和 PsA 的特征。然而,它们在疾病部位的分布不同,包括 SF 中 IL-22+CD4+T 细胞的频率低于皮肤和 PB,以及 ST 中缺乏 IL-22 表达,表明 Th17 和 Th22 细胞在 Ps 和 PsA 的发病机制中既有共同作用,也有不同作用。