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.