P048 Mucosal macrophages express elevated levels of HDAC9 in inflamed and uninflamed mucosa of Crohn’s disease, but not ulcerative colitis
M. Ghiboub1, J. de Bruyn1, K. Reedquist2, T. Radstake3, C. Wichers2, M. Wildenberg1, J. Broen3, G. D’Haens4, W. de Jonge1
1Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Center, Amsterdam, The Netherlands, 2Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands, 3Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands, 4Pediatric Gastroenterology and Nutrition, Amsterdam University Medical Center, Amsterdam, The Netherlands
Background
Histone deacetylases (HDACs) are a group of enzymes that control histone and non-histone deacetylation and influence inflammatory gene transcription. Certain members of the HDAC family control the function of macrophages and play an important role in immune response. In this study, we aimed to study the expression of HDACs in mucosal macrophages isolated from inflammatory bowel diseases (IBD) patients.
Methods
Both macroscopically inflamed and non-inflamed colon resection tissue were collected from 15 Crohn’s disease (CD) and nine ulcerative colitis (UC) patients operated on for therapy refractory disease. Of the CD patients, 53% had ileal and 47% ileocolonic disease. Of the UC patients, 44% had left-sided colitis and 56% pancolitis. Lamina propria was separated from the muscularis externa, and a targeted array for epigenetic enzymes was performed. To assess the relevance of HDAC9 gene expression in terms of protein level, immunofluorescence staining of HDAC9 protein was undertaken in tissue sections from inflamed and non-inflamed mucosa. CD68 was used as a pan-macrophage marker.
Results
From our array, expression of HDAC9 was significantly higher in the inflamed mucosa of CD patients compared with UC patients (
Conclusion
HDAC9 is member of class IIA HDAC superfamily that exerts pro-inflammatory properties. The inhibition of HDAC9 in experimental murine colitis clearly enhances regulatory T-cell function, suggesting a critical role for HDAC9 in breaching immune homeostasis (de Zoeten EF et al, 2009). We suggest here that HDAC9 can serve as an additional marker to distinguish CD from UC in tissue biopsies. Furthermore, we show for the first time that HDAC9 protein is expressed in mucosal macrophages of CD patients, indicating its potential in mediating macrophage inflammatory function in IBD. Further studies are currently being undertaken to elucidate the role of HDAC9 in CD pathogenesis.