Expression of Jak3, STAT1, STAT4, and STAT6 in inflammatory arthritis: unique Jak3 and STAT4 expression in dendritic cells in seropositive rheumatoid arthritis
Expression of Jak3, STAT1, STAT4, and STAT6 in inflammatory arthritis: unique Jak3 and STAT4 expression in dendritic cells in seropositive rheumatoid arthritis
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Jak3、STAT1、STAT4 和 STAT6 在炎性关节炎中的表达：血清阳性类风湿关节炎树突状细胞中独特的 Jak3 和 STAT4 表达
DOI：
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发表时间：
2005
影响因子：
27.4
通讯作者：
M. Smith
中科院分区：
文献类型：
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作者：
Jenny G Walker;M. Ahern;M. Coleman;H. Weedon;V. Papangelis;D. Beroukas;P. Roberts;M. Smith
背景：调节Jak-STAT信号可能为炎症性关节炎提供一种有效的治疗策略。目的：记录活动性类风湿关节炎（RA）、脊柱关节炎（SpA）和骨关节炎（OA）患者队列中Jak-STAT的表达，并将这些亚组与正常滑膜组织进行比较。方法：采用免疫组化方法检测RA、OA和SpA患者滑膜组织活检标本和组织学正常组织（每组10例）中Jak 3、STAT 1、STAT 4和STAT 6的表达。 使用免疫组织化学和免疫荧光进行表型分析。评估了表达Jak 3-STAT 4的RA患者的临床和血清学特征。结果：STAT 1、STAT 4和Jak 3蛋白在炎症性关节炎中表达普遍增加。相比之下，STAT 6表达相对异质。检测到血清阳性RA患者特有的CD 1a阳性树突状细胞亚群。这些细胞显示出Jak 3、STAT 4和STAT 6的强烈蛋白表达。结论：CD 1a阳性树突状细胞在血清阳性RA组织中强烈表达Jak 3、STAT 4和STAT 6，可能是树突状细胞活化早期的替代标志物，并提供了在滑膜水平识别RA的工具。Jak 3抑制可能是一个潜在的治疗目标，以防止树突状细胞成熟的RA。STAT 1在炎性关节炎中表达增加，表明其促凋亡和抗炎作用不能有效地对抗炎症。STAT 6在滑膜中的表达是异质性的，这表明除了任何抗炎作用之外，还可能具有同源平衡作用。
Background: Modulation of Jak-STAT signalling may provide an effective therapeutic strategy in inflammatory arthritis. Objective: To document Jak-STAT expression in a cohort of patients with active rheumatoid arthritis (RA), spondyloarthritis (SpA), and osteoarthritis (OA) and compare these subsets with normal synovial tissue. Methods: Synovial tissue biopsy specimens from patients with RA, OA, and SpA and histologically normal tissue (n = 10 in each arthritis group) were examined for the presence of Jak3, STAT1, STAT4, and STAT6 expression using immunohistochemistry. Phenotyping was performed using immunohistochemistry and immunofluorescence. Clinical and serological characteristics of patients with RA expressing Jak3-STAT4 were assessed. Results: STAT1, STAT4, and Jak3 protein expression was generally increased in inflammatory arthritis. In contrast, STAT6 expression was relatively heterogeneous. A subpopulation of CD1a positive dendritic cells unique to seropositive patients with RA was detected. These cells showed intense protein expression for Jak3, STAT4, and STAT6. Conclusion: CD1a positive dendritic cells intensely express Jak3, STAT4, and STAT6 in seropositive RA tissue and may be an alternative marker for dendritic cells in their early stages of activation as well as providing a tool for identifying RA at the level of the synovium. Jak3 inhibition may be a potential therapeutic target to prevent dendritic cell maturation in RA. STAT1 expression is increased in inflammatory arthritis, suggesting that its pro-apoptotic and anti-inflammatory effects cannot effectively counteract inflammation. STAT6 expression is heterogeneous in synovium, suggesting a possible homoeostatic role in addition to any anti-inflammatory effects.
影响因子：
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作者：
Ranjeny Thomas;P. Lipsky
通讯作者：
Ranjeny Thomas;P. Lipsky