Clinical Immunology Unit, Department of Immunology and Rheumatology, Joint Unit Hospices Civils de Lyon-bioMérieux, Hôpital Edouard Herriot, 5 place d'Arsonval, Lyon, France.
Ann Rheum Dis. 2010 Apr;69(4):755-60. doi: 10.1136/ard.2009.109991. Epub 2009 May 11.
FoxO3a is a transcriptional factor implicated in cell cycle regulation and apoptosis. Since rheumatoid arthritis (RA) is associated with apoptosis defects, the expression level, regulation and phosphorylation status of FoxO3a was investigated in blood and synovium from patients with RA.
In microarray experiments, an overexpression of FoxO3a mRNA was observed in blood from patients with RA compared with healthy controls. FoxO3a mRNA expression was quantified in polymorphonuclear cells (PMNs) and peripheral blood mononuclear cells from patients with RA by qRT-PCR. Total FoxO3a and phosphorylated FoxO3a (pFoxO3a) protein expression was analysed in blood leucocytes from patients with RA versus controls and in synovium from patients with RA versus patients with osteoarthritis (OA) by immunostaining.
FoxO3a mRNA and protein expression levels were increased in blood from patients with RA compared with controls. FoxO3a overexpression was primarily observed in PMNs. In synovium from patients with RA, both total and inactive phosphorylated FoxO3a proteins were detected. FoxO3a was detected primarily in the sublining T lymphocytes of synovium from patients with RA compared with the lining layer tissue from patients with RA and OA, underlying a role for FoxO3a proteins in inflammation in RA.
The overexpression of FoxO3a in blood from patients with RA, particularly in PMNs, suggests a potential role for this gene in the pathogenesis of RA through increased survival of blood PMNs. In synovium from patients with RA, FoxO3a mainly detected in inflammatory aggregates may also regulate the chronic survival of T lymphocytes.
FoxO3a 是一种参与细胞周期调控和细胞凋亡的转录因子。由于类风湿关节炎（RA）与细胞凋亡缺陷有关，因此研究了 FoxO3a 在 RA 患者血液和滑膜中的表达水平、调节和磷酸化状态。
在微阵列实验中，与健康对照者相比，RA 患者血液中的 FoxO3a mRNA 表达升高。通过 qRT-PCR 定量检测 RA 患者多形核细胞（PMN）和外周血单个核细胞中的 FoxO3a mRNA 表达。通过免疫染色分析 RA 患者血液白细胞和 RA 患者与骨关节炎（OA）患者滑膜中总 FoxO3a 和磷酸化 FoxO3a（pFoxO3a）蛋白的表达。
与对照组相比，RA 患者血液中的 FoxO3a mRNA 和蛋白表达水平升高。FoxO3a 过表达主要在 PMN 中观察到。在 RA 患者的滑膜中，检测到总 FoxO3a 和无活性磷酸化 FoxO3a 蛋白。FoxO3a 主要在 RA 患者滑膜的亚衬里 T 淋巴细胞中检测到，而在 RA 和 OA 患者的衬里层组织中则检测不到，这表明 FoxO3a 蛋白在 RA 炎症中发挥作用。
RA 患者血液中 FoxO3a 的过度表达，特别是在 PMN 中，提示该基因可能通过增加血液 PMN 的存活而在 RA 的发病机制中发挥作用。在 RA 患者的滑膜中，主要在炎症聚集物中检测到的 FoxO3a 也可能调节 T 淋巴细胞的慢性存活。
