Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Ann Rheum Dis. 2010 Dec;69(12):2213-6. doi: 10.1136/ard.2010.129999. Epub 2010 Aug 10.
To investigate the role of X chromosomal inactivation (XCI) in systemic sclerosis (SSc) and its effects on forkhead box P3 (Foxp3) expression in T regulatory cells (Tregs).
217 women with SSc and 107 healthy women (controls) were included in the study. From these subjects, DNA was isolated from total peripheral blood mononuclear cells, plasmacytoid dendritic cells, T cells, B cells, myeloid dendritic cells and monocytes after magnetic bead separation. All samples were assessed for skewed XCI patterns with the Human Androgen Receptor Assay. The outcome was assessed by linear regression. CD4+ CD25+ cells were then isolated and intracellular Foxp3 expression was assessed by flow cytometry.
Skewing was not associated with increased age in patients with SSc, in contrast to the control population (r = 0.45, p < 0.0001). Taking this into account, a significantly higher frequency of skewed XCI was found in patients with SSc compared with controls (p = 0.001). No difference in skewing was observed between the immune cell subsets. In addition, a higher concentration of Foxp3+ cells exhibiting a lower Foxp3 mean fluorescence intensity was found in the patients with SSc, with profound XCI skewing (both p < 0.001) associated with less efficient suppressive activity (p=0.012).
Skewed XCI plays a role in susceptibility to SSc, is not restricted and influences Foxp3 expression and the suppressive capacity of Tregs.
探讨 X 染色体失活（XCI）在系统性硬化症（SSc）中的作用及其对调节性 T 细胞（Tregs）中叉头框 P3（Foxp3）表达的影响。
本研究纳入了 217 名女性 SSc 患者和 107 名健康女性（对照组）。从这些受试者中，用磁珠分离法从总外周血单个核细胞、浆细胞样树突状细胞、T 细胞、B 细胞、髓样树突状细胞和单核细胞中分离出 DNA。用人类雄激素受体测定法评估所有样本的偏斜 XCI 模式。结果通过线性回归进行评估。然后分离 CD4+CD25+细胞，并通过流式细胞术评估细胞内 Foxp3 表达。
与对照组相比，SSc 患者的偏斜与年龄增加无关（r = 0.45，p < 0.0001）。考虑到这一点，发现 SSc 患者的偏斜 XCI 频率明显高于对照组（p = 0.001）。在免疫细胞亚群之间未观察到偏斜的差异。此外，还发现 SSc 患者中表现出较低 Foxp3 平均荧光强度的 Foxp3+细胞的浓度较高，且存在深刻的 XCI 偏斜（均 p < 0.001）与抑制活性降低相关（p=0.012）。
偏斜 XCI 在 SSc 的易感性中起作用，不受限制，影响 Foxp3 表达和 Tregs 的抑制能力。
