title: Strong Upregulation of AIM2 and IFI16 Inflammasomes in the Mucosa of Patients with Active Inflammatory Bowel Disease.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Expression of genes encoding inflammasome sensor subunits was investigated in colonic mucosal biopsies from 2 cohorts of patients with IBD and controls.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: *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.
authors: Wiebe
authors: W
authors: Vanhove
authors: Paul M
authors: PM
authors: Peeters
authors: Dominiek
authors: D
authors: Staelens
authors: Anica
authors: A
authors: Schraenen
authors: Jan
authors: J
authors: Van der Goten
authors: Isabelle
authors: I
authors: Cleynen
authors: Sebastiaan
authors: S
authors: De Schepper
authors: Leentje
authors: L
authors: Van Lommel
authors: Niki L
authors: NL
authors: Reynaert
authors: Frans
authors: F
authors: Schuit
authors: Gert
authors: G
authors: Van Assche
authors: Marc
authors: M
authors: Ferrante
authors: Gert
authors: G
authors: De Hertogh
authors: Emiel F M
authors: EF
authors: Wouters
authors: Paul
authors: P
authors: Rutgeerts
authors: Séverine
authors: S
authors: Vermeire
authors: Kris
authors: K
authors: Nys
authors: Ingrid
authors: I
authors: Arijs
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D016022:Case-Control Studies; D020170:Caspase 1 / Q000378:metabolism; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D024243:HMGB1 Protein / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D058847:Inflammasomes / Q000235:genetics*; D015212:Inflammatory Bowel Diseases / Q000473:pathology*; D007413:Intestinal Mucosa / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: C410167:AIM2 protein, human; D004268:DNA-Binding Proteins; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D058847:Inflammasomes; D009687:Nuclear Proteins; D010750:Phosphoproteins; C076700:IFI16 protein, human; D020170:Caspase 1