Immunology and Allergy, University Hospital and School of Medicine, 4 rue Gabrielle Perret Gentil, Geneva 1211, Switzerland.
Arthritis Res Ther. 2011;13(5):R166. doi: 10.1186/ar3486. Epub 2011 Oct 13.
T cell abnormalities have been associated with the pathogenesis of systemic sclerosis (SSc). Recently, besides T helper (Th)17 cells, the Th22 subset has been identified in humans. Our purpose was to investigate the pattern of cytokines produced and chemokine-receptors expressed by peripheral blood (PB) Th cells in SSc and healthy donors (HD) focusing on cells producing interleukin (IL)-17 and IL-22 and to identify specific clinical associations.
Clinical data and peripheral blood were collected in 33 SSc individuals and 29 HD. IL-17A, IL-22, interferon gamma (IFN-γ), IL-4 production, the chemokine receptors CCR4, CCR6, CCR10, CXCR3 expression and the CD161 Th17 cell marker were assessed by multiparametric flow cytometry in PB CD4+ T cells. Intracellular cytokine accumulation was further investigated in CD4+ T cells expanded in vitro for seven days.
The frequency of Th22, Th17, Th2, but not Th1 cells, was significantly increased in SSc individuals compared to HD. The percentage of CD161+CD4+ T cells was increased in SSc and correlated with the percentage of IL-17A producing cells. Moreover, the expression of the skin- and lung-homing chemokine receptor CCR6 correlated with the frequency of IL-22 and IL-17A-producing cells in SSc but not in HD. Finally, SSc interstitial lung disease (ILD) was strongly associated with higher numbers of IL-22 and, to a lesser extent, IL-17A-producing cells.
IL-22 and IL-17A-producing T cells with skin- and lung-homing capabilities are characteristically increased in SSc. These findings support the hypothesis that Th22, in addition to Th17 cells, may be involved in pathological processes leading to SSc. While the association between IL-22 producing cells and ILD needs to be assessed in larger cohorts of patients, the increased frequency of Th22 cells appears to be a useful novel biomarker in SSc.
T 细胞异常与系统性硬化症（SSc）的发病机制有关。最近，除了辅助性 T 细胞（Th）17 细胞外，人类还发现了 Th22 亚群。我们的目的是研究 SSc 和健康供体（HD）外周血（PB）Th 细胞产生的细胞因子和趋化因子受体的模式，重点关注产生白细胞介素（IL）-17 和 IL-22 的细胞，并确定具体的临床相关性。
在 33 名 SSc 个体和 29 名 HD 中收集临床数据和外周血。通过多参数流式细胞术检测 PB CD4+T 细胞中 IL-17A、IL-22、干扰素γ（IFN-γ）、IL-4 的产生、趋化因子受体 CCR4、CCR6、CCR10、CXCR3 的表达和 CD161 Th17 细胞标志物。进一步研究 CD4+T 细胞在体外培养七天后的细胞内细胞因子积累情况。
与 HD 相比，SSc 个体中 Th22、Th17、Th2 细胞的频率显著增加，但 Th1 细胞的频率没有增加。CD161+CD4+T 细胞的百分比在 SSc 中增加，并与产生 IL-17A 的细胞百分比相关。此外，皮肤和肺归巢趋化因子受体 CCR6 的表达与 SSc 中 IL-22 和 IL-17A 产生细胞的频率相关，但与 HD 无关。最后，SSc 间质性肺病（ILD）与较高数量的 IL-22 和较少数量的 IL-17A 产生细胞强烈相关。
具有皮肤和肺归巢能力的 IL-22 和 IL-17A 产生 T 细胞在 SSc 中特征性增加。这些发现支持了 Th22 细胞除 Th17 细胞外，可能参与导致 SSc 的病理过程的假说。虽然需要在更大的患者队列中评估产生 IL-22 的细胞与 ILD 之间的关系，但 Th22 细胞的频率增加似乎是 SSc 的一种有用的新型生物标志物。
