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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Epithelial-derived IL-33 and its receptor ST2 are dysregulated in ulcerative colitis and in experimental Th1/Th2 driven enteritis
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Epithelial-derived IL-33 and its receptor ST2 are dysregulated in ulcerative colitis and in experimental Th1/Th2 driven enteritis

机译：在溃疡性结肠炎和实验性Th1 / Th2驱动的肠炎中，上皮来源的IL-33及其受体ST2失调

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摘要

IL-33 is a novel member of the IL-1 family and ligand for the IL-1 receptor-related protein, ST2. Recent evidence suggests that the IL-33/ST2 axis plays a critical role in several autoimmune and inflammatory disorders; however, its role in inflammatory bowel disease (IBD) has not been clearly defined. We characterized IL-33 and ST2 expression and modulation after conventional anti-TNF therapy in Crohn's disease and ulcerative colitis (UC) patients and investigated the role of IL-33 in SAMPVYitFc (SAMP) mice, a mixed Th1/Th2 model of IBD. Our results showed a specific increase of mucosal IL-33 in active UC, localized primarily to intestinal epithelial cells (IEC) and colonic inflammatory infiltrates. Importantly, increased expression of full-length IL-33, representing the most bio-active form, was detected in UC epithelium, whereas elevated levels of cleaved IL-33 were present in IBD serum. ST2 isoforms were differentially modulated in UC epithelium, and sST2, a soluble decoy receptor with anti-inflammatory properties, was also elevated in IBD serum. Inf liximab (anti-TNF) treatment of UC decreased circulating IL-33 and increased sST2, whereas stimulation of HT-29 IEC confirmed IL-33 and sST2 regulation by TNF. Similarly, IL-33 significantly increased and correlated with disease severity, and potently induced IL-5, IL-6, and IL-17 from mucosal immune cells in SAMP mice. Taken together, the IL-33/ST2 system plays an important role in IBD and experimental colitis, is modulated by anti-TNF therapy, and may represent a specific biomarker for active UC.
机译：IL-33是IL-1家族的新成员，并且是IL-1受体相关蛋白ST2的配体。最近的证据表明，IL-33 / ST2轴在几种自身免疫和炎性疾病中起关键作用。然而，其在炎症性肠病（IBD）中的作用尚未明确。我们在克罗恩病和溃疡性结肠炎（UC）患者中常规抗TNF治疗后表征了IL-33和ST2的表达和调控，并研究了IL-33在SAMPVYitFc（SAMP）小鼠（IBD的Th1 / Th2混合模型）中的作用。我们的研究结果显示，活跃的UC中黏膜IL-33的特异性增加，主要位于肠道上皮细胞（IEC）和结肠炎性浸润。重要的是，在UC上皮细胞中检测到代表最强生物活性形式的全长IL-33表达增加，而IBD血清中IL-33的裂解水平升高。 ST2亚型在UC上皮细胞中受到差异调节，而sST2是具有抗炎特性的可溶性诱饵受体，在IBD血清中也升高。 UC的Inf liximab（抗TNF）治疗可降低循环IL-33并增加sST2，而刺激HT-29 IEC则证实TNF调节IL-33和sST2。同样，IL-33显着增加并与疾病严重程度相关，并有效诱导SAMP小鼠粘膜免疫细胞产生IL-5，IL-6和IL-17。两者合计，IL-33 / ST2系统在IBD和实验性结肠炎中起重要作用，受抗TNF治疗调节，可能代表活性UC的特定生物标记。

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    Luca Pastorelli; Rekha R. Garg; Sharon B. Hoang; Luisa Spina; Benedetta Mattioli; Melania Scarpa; Claudio Fiocchi; Maurizio Vecchi; Theresa T. Pizarro;

  • 作者单位

    Department of Pathology, Case Western Reserve University, Cleveland, OH 44106 Gastroenterology and Gastrointestinal Endoscopy Unit, Istituto Di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, San Donato Milanese 20097, Italy Department of Medical Science, University of Milan School of Medicine, Milan 20122, Italy;

    rnDepartment of Pathology, Case Western Reserve University, Cleveland, OH 44106;

    rnDepartment of Pathology, Case Western Reserve University, Cleveland, OH 44106;

    rnGastroenterology and Gastrointestinal Endoscopy Unit, Istituto Di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, San Donato Milanese 20097, Italy Department of Medical Science, University of Milan School of Medicine, Milan 20122, Italy;

    rnDepartment of Pathology, Case Western Reserve University, Cleveland, OH 44106;

    rnDepartment of Pathobiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195;

    rnDepartment of Pathobiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195;

    rnGastroenterology and Gastrointestinal Endoscopy Unit, Istituto Di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, San Donato Milanese 20097, Italy Department of Medical Science, University of Milan School of Medicine, Milan 20122, Italy;

    rnDepartment of Pathology, Case Western Reserve University, Cleveland, OH 44106;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    inflammatory bowel disease; anti-TNF therapy; SAMP1/YitFc mouse model;

    机译：炎症性肠病;抗TNF治疗;SAMP1 / YitFc小鼠模型;

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