Interleukin (IL)-17AA Reduces Pro-Inflammatory Cytokine Production By Inflammatory Bowel Disease Mucosa Cultured Ex Vivo. Elucidating target cells involved in this effect.

CURCIARELLO RENATA; BIANCHERI PAOLO; ROCCA ANDRES; SAMBUELLI ALICIA; CORREA GUSTAVO; YANTORNO MARTÍN; CHOPITA NÉSTOR; MACDONALD THOMAS; DOCENA GUILLERMO H.

Buenos Aires

Congreso; First International Congress of LASID FAIC SAI, IV Meeting LASID and LXIII Congreso Anual de la Sociedad Argentina de Inmunología; 2015

SAI

Inflammatory bowel diseases (IBD) are chronic and immune-mediated disorders. Interleukin (IL)-17A was found to be increased in mucosal lesions of IBD patients. IL-17 cytokines family includes 5 members, which constitute dimers in their active form. IL-17A shares 50% homology with IL-17F, they may form IL-17AA and IL-17FF homodimers or IL-17A/F heterodimer. Since the role of IL-17 dimers is unknown in IBD, we studied the pro-inflammatory effect of IL-17AA, IL-17FF and IL-17-A/F in intestinal samples of ulcerative colitis (UC) and Crohn?s disease (CD) patients.Inflamed colonic biopsies from 26 IBD patients (13 UC and 13 CD) were cultured ex vivo for 24 hours with IL-17AA, IL-17FF or IL-17A/F (1 ng/ml). Mucosal myofibroblasts isolated from the inflamed colon of 5 CD and 5 UC patients were cultured with increasing concentrations (1-100 ng/ml) of each dimer or tumor necrosis factor (TNF)- (20 ng/ml) as control. IL-6, IL-8 and TNF-α were measured in culture supernatants by ELISA.We found that IL-17AA, but not IL-17FF, significantly reduced IL-6 and IL-8 production, whereas IL-17A/F only decreased IL-8 release. As expected, TNF- stimulation significantly increased IL-6 and IL-8 production in CD and UC myofibroblasts. However, none of the dimers modified the secretion of IL-6 and IL-8 at these concentrations.In conclusion, we found that IL-17AA exerted an anti-inflammatory action on inflamed IBD biopsies, but this effect would not be directly mediated by myofibroblasts. Further studies are being conducted to investigate a synergistic effect of IL-17 and TNF-α and epithelial cells as target cells for IL-17AA in IBD mucosa.