INTERLEUKIN (IL)-17 MODULATES THE PRO-INFLAMMATORY RESPONSE OF COLONIC MYOFIBROBLASTS FROM PATIENTS WITH INFLAMMATORY BOWEL DISEASE

CURCIARELLO R; BIANCHERI PAOLO; SOL ROLDAN A; DUBOIS C; ROCCA ANDRES; SAMBUELLI ALICIA; CORREA GUSTAVO; YANTORNO MARTÍN; VILLAVERDE AUGUSTO; TUFARE F; HERMOSO RAMALLO MARCELA; MACDONALD T; DOCENA G

CABA

Congreso; Reunión Conjunta de Sociedades de Biociencia, LXV Reunión Annual de la Sociedad Argentina de Inmunología; 2017

Inflammatory bowel disease (IBD), mainly Crohn's disease (CD) and ulcerative colitis (UC), are chronic intestinal disorders in which pro-inflammatory cytokines are involved. Th17 cells and IL-17 are abundantly found in the inflamed intestinal mucosa. Although IL-17A has been reported as a pathogenic factor in IBD, the exact role for IL-17 in IBD remains controversial. We have previously shown that IL-17 dimmers (IL-17AA, FF and AF) are differentially produced in UC and CD lamina propria, and the anti-inflammatory properties of IL-17AA. In order to identify target cells for IL-17 in IBD intestinal mucosa, we aimed to study the effect of IL-17A, IL-17F and IL-17A/F on human colonic myofibroblasts, which may be pro- or anti-inflammatory cells. Myofibroblasts were isolated from intestinal biopsies or surgical samples from IBD adult patients (UC n=3, CD n=4) and healthy donors (HC n=1). Cells were stimulated with recombinant human IL-17A, IL-17F or IL-17AF (1ng/ml), in combination with TNF (1ng/ml) or medium as control. Secreted IL-6 and IL-8 were quantified by ELISA, and IL-33 and ST2 gene expression was quantified by qPCR as pro-inflammatory markers. We found that IL-17 dimmers did not induce IL-6 nor IL-8 secretion, however only IL-17A combined with TNF significantly diminished IL-6 and IL-8 production by UC and CD myofibroblasts compared with TNF alone (p