Interleukin-9 Overexpression and Th9 Polarization Characterize the Inflamed Gut, the Synovial Tissue, and the Peripheral Blood of Patients With Psoriatic Arthritis
Interleukin-9 Overexpression and Th9 Polarization Characterize the Inflamed Gut, the Synovial Tissue, and the Peripheral Blood of Patients With Psoriatic Arthritis
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DOI：
10.1002/art.39649
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发表时间：
2016-08-01
影响因子：
13.3
通讯作者：
Triolo, Giovanni
中科院分区：
文献类型：
--
作者：
Ciccia, Francesco;Guggino, Giuliana;Triolo, Giovanni
Objective.目的探讨Th 9相关细胞因子在银屑病关节炎（PsA）患者中的表达及组织分布。从PsA患者、HLA-B27阳性强直性脊柱炎（AS）患者、克罗恩病（CD）患者和健康对照者的肠道活检样本中进行Th 1、Th 17和Th 9细胞因子的定量基因表达分析。通过免疫组织化学和共聚焦显微镜评价白细胞介素-23（IL-23）、IL-17、IL-22、IL-9和IL-9受体（IL-9 R）的表达和组织分布。采用流式细胞术检测外周血、固有层和滑液单核细胞中Th 9细胞的比例。在功能性体外研究中评估上皮细胞上IL-9 R表达的功能相关性。我们还研究了银屑病患者滑膜组织中的Th 9细胞。PsA患者的亚临床肠道炎症的特征在于明显的Th 17和Th 22，而不是Th 1，极化免疫应答。与AS和CD不同，在PsA肠道中观察到IL-9的强烈且显著的上调，特别是在浸润的单核细胞、高内皮微静脉和潘氏细胞中。IL-9阳性单核细胞被证明是在大部分的Th 9细胞。IL-9过度表达伴随着显着的潘氏细胞增生。Paneth细胞强烈过表达IL-9 R，并且用IL-9刺激从PsA患者分离的上皮细胞导致α-防御素5和IL-23 p19的过表达。在PsA患者中还观察到α 4 β 71 Th 9细胞的外周和滑膜扩增。IL-9和IL-9 R在滑膜组织中表达增加。强烈的IL-9/Th 9极化似乎是PsA患者的主要免疫学特征。
Objective. To investigate the expression and tissue distribution of Th9-related cytokines in patients with psoriatic arthritis (PsA).Methods. Quantitative gene expression analysis of Th1, Th17, and Th9 cytokines was performed in intestinal biopsy samples obtained from patients with PsA, HLA-B27-positive patients with ankylosing spondylitis (AS), patients with Crohn's disease (CD), and healthy controls. Expression and tissue distribution of interleukin-23 (IL-23), IL-17, IL-22, IL-9, and IL-9 receptor (IL-9R) were evaluated by immunohistochemistry and confocal microscopy. Flow cytometry was used to study the frequency of Th9 cells among peripheral blood, lamina propria, and synovial fluid mononu-clear cells. The functional relevance of IL-9R expression on epithelial cells was assessed in functional in vitro studies. Th9 cells in synovial tissue from patients with PsA were also studied.Results. Subclinical gut inflammation in PsA patients was characterized by a clear Th17 and Th22, but not Th1, polarized immune response. Unlike AS and CD, a strong and significant up-regulation of IL-9 was observed in PsA gut, especially among infiltrating mononuclear cells, high endothelial venules, and Paneth cells. IL-9-positive mononuclear cells were demonstrated to be in large part Th9 cells. IL-9 overexpression was accompanied by significant Paneth cell hyperplasia. Paneth cells strongly overexpressed IL-9R, and stimulation of epithelial cells, isolated from PsA patients, with IL-9 resulted in overexpression of alpha-defensin 5 and IL-23p19. Peripheral and synovial expansion of alpha 4 beta 71 Th9 cells was also observed in patients with PsA. Increased expression of IL-9 and IL-9R was also found in synovial tissue.Conclusion. Strong IL-9/Th9 polarization seems to be the predominant immunologic signature in patients in PsA.