Interleukin (IL)-17 modulates the pro-inflammatory response of colonic myofibroblasts from patients with inflammatory bowel disease

CURCIARELLO R; ROLDÁN AS; BIANCHERI P; CAMACHO K; ANDRÉS ROCCA; SAMBUELLI A; GUSTAVO J. CORREA; YANTORNO M; VILLLAVERDE A; TUFARE; HERMOSO RAMELLO M; MACDONALD TT; DOCENA G

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias, LXV Reunión Anual de la Sociedad Argentina de Inmunología; 2017

Inflammatory boweldisease (IBD), mainly Crohn's disease (CD) and ulcerative colitis(UC), are chronic intestinal disorders in which pro-inflammatorycytokines are involved. Th17 cells and IL-17are abundantly found in the inflamed intestinal mucosa. Although IL-17A hasbeen reported as a pathogenic factor in IBD, the exact role for IL-17 in IBDremains controversial. We have previously shown that IL-17 dimmers (IL-17AA, FFand 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, weaimed 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 surgicalsamples 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-8were quantified by ELISA. And IL-33 and ST2 gene expression was quantified byqPCR as pro-inflammatory markers. We found that IL-17 dimmers did not induce IL-6 nor IL-8 secretion, howeveronly IL-17A combined with TNF significantly diminished IL-6 and IL-8 productionby UC and CD myofibroblasts compared with TNF alone (p<0.1). Besides, IL-17 dimmersinduced a two- to eight-fold increase in IL-33 and ST2 expression on UC and CD fibroblasts.In conclusion, we found that intestinal myofibroblasts from IBD patientsare target cells for IL-17 and IL-17 dimmers differentially modulated thepro-inflammatory response. Moreover, CD fibroblasts expressed IL-33 and ST2,which has been described so far as exclusively produced by UC fibroblasts.These findings suggest that IL-17 may play different roles in the pathogenesisof IBD, depending on the cell subset affected.