ICMI 2015

F.13 Identification of potential therapeutic macrophage-related targets for inflammatory bowel disease (IBD)

Friday, July 17, 2015
Grand Hall and Gallery, Ground Floor & 1st Floor (Maritim Hotel)
Francesca Ammoscato , Barts and The London School of Medine and Dentistry, London, United States
Aneta Kucik , Barts and The London School of Medicine and Dentistry, London, United Kingdom
Paolo Biancheri, MD , Barts and The London School of Medicine and Dentistry, London, United Kingdom
Paolo Giuffrida , Clinica Medica I Laboratorio di Gastroenterologia Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
Laurens Kruidenier, PhD , Takeda Cambridge Limited, Cambridge, United Kingdom
Thomas MacDonald, PhD , Barts and the London School of Medicine and Dentistry, London, United Kingdom
Background & Aims: Intestinal macrophages play an important role in IBD, however their gene expression profile is unknown. We therefore performed gene arrays on gut macrophages isolated from IBD patients and control subjects (HCs).

Methods: 84 genes were analyzed in lamina propria CD33+ macrophages isolated from the inflamed colon of 11 IBD patients and from the normal colon of 10 HCs. IL-24 was measured in the supernatants of IBD and control biopsies cultured ex vivo, and TNF-α concentration was determined in the supernatants of inflamed IBD biopsies cultured ex vivo with rhIL-24.

Results: IL24, IL21, INHBA, TNFSF8, LTB and IL10 expression was significantly higher in IBD compared to HC intestinal macrophages, whereas MSTN, IFNA4, BMP5, BMP2 and PDGFA expression was significantly down-regulated in IBD macrophages. IL-24 was significantly higher in inflamed IBD (928.5 ± 171.3 pg/ml) than in HC (273.2 ± 37.8 pg/ml) biopsy supernatants. Compared to medium alone, ex vivo culture with rhIL-24 significantly increased TNF-α production by inflamed IBD biopsies (119.9 ± 41.0 and 436.9 ± 115.7 pg/ml, respectively).

Conclusions: IBD gut macrophages show a dysregulated immune gene profile, which we are functionally evaluating in the search for macrophage-related therapeutic targets. Preliminary data show that IL-24 is up-regulated in IBD mucosa and promotes TNF-α release by IBD biopsies cultured ex vivo.