Interleukin (IL)-17AA reduces pro-inflammatory cytokine production by inflammatory bowel disease mucosa cultured ex vivo. Elucidating target cells involved in this effect

RENATA CURCIARELLO; PAOLO BIANCHERI; ANDRÉS ROCCA; ALICIA SAMBUELLI; GUSTAVO J. CORREA; MARTÍN YANTORNO; NÉSTOR CHOPITA; THOMAS T, MACDONALD; GUILLERMO, DOCENA

Ciudad Autónoma de Buenos Aires

Congreso; IV LASID meeting, LXIII Argentinean Society of Immunology meeting and II French Society for Immunology Meeting; 2015

LASID FAIC SAI

Inflammatory bowel disease (IBD) comprises chronic and immune-mediateddisorders. Interleukin (IL)-17A was found to be increased in mucosal lesions ofIBD patients. IL-17 cytokines family includes 5 members, which constitutedimers in their active form. IL-17A shares 50% homology with IL-17F, they mayform IL-17AA and IL-17FF homodimers or IL-17A/F heterodimer. Since the role ofIL-17 dimers is unknown in IBD, we studied the pro-inflammatory effect ofIL-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) werecultured ex vivo for 24 hours with IL-17AA,IL-17FF or IL-17A/F (1 ng/ml). Mucosal myofibroblasts isolated from theinflamed colon of 5 CD and 5 UC patients were cultured with increasingconcentrations (1-100 ng/ml) of each dimer or tumor necrosis factor (TNF)-a (20 ng/ml) as control. IL-6 and IL-8 were measured in culturesupernatants by ELISA.We found that IL-17AA, but not IL-17FF, significantly reduced IL-6 andIL-8 production, whereas IL-17A/F only decreased IL-8 release. As expected,TNF-a stimulation significantly increased IL-6 and IL-8 production in CD andUC myofibroblasts. However, none ofthe dimers modified the secretion of IL-6 and IL-8 at these concentrations.In conclusion, we found that IL-17AA exerted an anti-inflammatory actionon inflamed IBD biopsies, but this effect would not be directly mediated bymyofibroblasts. Further studies are being conducted to investigate asynergistic effect of IL-17 and TNF-α, and epithelial cells as target cells for IL-17AA in IBD mucosa.