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: Wiebe Vanhove, Paul M Peeters, Dominiek Staelens, Anica Schraenen, Jan Van der Goten, Isabelle Cleynen, Sebastiaan De Schepper, Leentje Van Lommel, Niki L Reynaert, Frans Schuit, Gert Van Assche, Marc Ferrante, Gert De Hertogh, Emiel F M Wouters, Paul Rutgeerts, Séverine Vermeire, Kris Nys, Ingrid Arijs
• Journal: Inflammatory bowel diseases (Inflamm Bowel Dis) Vol. 21 Issue 11 Pg. 2673-82 (Nov 2015) ISSN: 1536-4844 [Electronic] England
• PMID: 26313692 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• AIM2 protein, human
• DNA-Binding Proteins
• HMGB1 Protein
• HMGB1 protein, human
• Inflammasomes
• Nuclear Proteins
• Phosphoproteins
• IFI16 protein, human
• Caspase 1

Topics

• Adult
• Aged
• Biopsy
• Case-Control Studies
• Caspase 1 (metabolism)
• Cohort Studies
• DNA-Binding Proteins (genetics, metabolism)
• Epithelial Cells (metabolism)
• Female
• HMGB1 Protein (metabolism)
• Humans
• Immunity, Innate
• Inflammasomes (genetics)
• Inflammatory Bowel Diseases (pathology)
• Intestinal Mucosa (pathology)
• Male
• Middle Aged
• Nuclear Proteins (genetics, metabolism)
• Phosphoproteins (genetics, metabolism)
• Signal Transduction
• Transcriptional Activation
• Up-Regulation