Vanhove Wiebe, Peeters Paul M, Staelens Dominiek, Schraenen Anica, Van der Goten Jan, Cleynen Isabelle, De Schepper Sebastiaan, Van Lommel Leentje, Reynaert Niki L, Schuit Frans, Van Assche Gert, Ferrante Marc, De Hertogh Gert, Wouters Emiel F M, Rutgeerts Paul, Vermeire Séverine, Nys Kris, Arijs Ingrid
*Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, KU Leuven, Leuven, Belgium; †Department of Respiratory Medicine, Maastricht University Medical Centre+, Maastricht University, Maastricht, the Netherlands; ‡IUF - Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany; §Gene Expression Unit, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium; and ‖Translational Cell & Tissue Research, Department of Imaging & Pathology, KU Leuven, Leuven, Belgium.
Inflamm Bowel Dis. 2015 Nov;21(11):2673-82. doi: 10.1097/MIB.0000000000000535.
Inflammatory bowel disease (IBD) is characterized by a chronic inflammation of the gut, partly driven by defects in the innate immune system. Considering the central role of inflammasome signaling in innate immunity, we studied inflammasome components in IBD mucosa.
Expression of genes encoding inflammasome sensor subunits was investigated in colonic mucosal biopsies from 2 cohorts of patients with IBD and controls.
A significant upregulation (>2-fold change in expression, false discovery rate <0.05) of the PYHIN inflammasomes AIM2 and IFI16 in active IBD versus controls was found. Also IFI16 was significantly increased in inactive IBD versus controls. Moreover, responders to anti-tumor necrosis factor therapy showed decreased expression of these inflammasomes although IFI16 remained significantly increased in responders showing endoscopic healing versus controls. AIM2 was mainly expressed in epithelial cells, whereas IFI16 was expressed in both lymphocytes and epithelial cells. Functional activation of predominant AIM2/IFI16-mediated inflammasomes in active IBD colon was shown by the presence of the downstream effectors CASP1 and HMGB-1 in inflamed mucosa.
Our results highlight the importance of PYHIN inflammasome signaling in IBD and also link anti-tumor necrosis factor responsiveness to inflammasome signaling. Together, this points to the potential value of the inflammasome pathway as a new therapeutic target for IBD treatment.
炎症性肠病（IBD）的特征是肠道慢性炎症，部分由先天性免疫系统缺陷所致。鉴于炎性小体信号在先天性免疫中的核心作用，我们研究了IBD黏膜中的炎性小体成分。
在两组IBD患者和对照组的结肠黏膜活检组织中，研究编码炎性小体传感器亚基的基因表达情况。
发现与对照组相比，活动期IBD患者中PYHIN炎性小体AIM2和IFI16显著上调（表达变化>2倍，错误发现率<0.05）。与对照组相比，非活动期IBD患者的IFI16也显著增加。此外，抗肿瘤坏死因子治疗的应答者这些炎性小体的表达降低，不过在实现内镜愈合的应答者中，IFI16与对照组相比仍显著增加。AIM2主要在上皮细胞中表达，而IFI16在淋巴细胞和上皮细胞中均有表达。在活动期IBD结肠中，通过炎症黏膜中存在下游效应物CASP1和HMGB-1，证实了主要由AIM2/IFI16介导的炎性小体的功能激活。
我们的研究结果突出了PYHIN炎性小体信号在IBD中的重要性，并将抗肿瘤坏死因子反应性与炎性小体信号联系起来。总之，这表明炎性小体途径作为IBD治疗新靶点的潜在价值。
