IL-33 AND THE PRO-INFLAMATORY RESPONSE OF COLONIC FIBROBLASTS FROM PATIENTS WITH INFLAMMATORY BOWEL DISEASE ARE MODULATED BY INTERLEUKIN-17

ANA SOL ROLDÁN; ALICIA SAMBUELLI; FERNANDO CHIRDO; GUILLERMO HORACIO DOCENA; FEDERICO PÉREZ; SANTIAGO BRAYER; MARTÍN YANTORNO; THOMAS T. MACDONALD; RENATA CURCIARELLO; KAREN DUBOIS CAMACHO; GUSTAVO J. CORREA; MARCELA HERMOSO RAMELLO

Cancun

Congreso; XII Congress of the Latin American Association of Immunology & XXIII Congress of the Mexican Society of Immunology. Cancun Quintana Roo, Mexico, 14 May - 18 May, 2018; 2018

Rosana Pelayo, Mexican Institute for Social Security, Puebla, Mexico.

Inflammatory bowel diseases (IBD), mainly Crohn´s disease (CD) and ulcerative colitis (UC), are chronic intestinal disorders caused by environmental and genetic factors. The gut-associated immune system is permanently activated in IBD, leading to an increase of pro-inflammatory cytokines, mediating immune cell activation/proliferation and extracellular matrix remodeling processes that cause the intestinal lesions (abscesses, fistulae, fibrosis and stenosis). Even though it is widely known that cytokines are involved in the fibrotic process, currently no anti-inflammatory therapy is available to modulate or reverse fibrosis.Th17 cells and IL-17 are abundantly found in the inflamed intestinal mucosa, although IL-17A has been reported as a mediator of IBD, its exact role remains unclear. We have previously shown that IL-17 dimmers (IL-17AA, FF and AF) are differentially produced by UC and CD lamina propria cells, and even the anti-inflammatory properties of IL-17AA. Additionally, IL-33 and its receptor ST2 are increased in inflamed mucosa from UC patients and in a lesser extent, from CD patients. We have found that activated intestinal myofibroblasts trigger the ulcerative lesions in UC, but not in CD, while secreting IL-33, and thus supporting a functional role for IL-33 in ulceration and wound healing in UC.In order to identify target cells for IL-17 in IBD intestinal mucosa, we studied the effect of IL-17A, IL-17F and IL-17A/F on the inflammatory response of human colonic myofibroblasts. Additionally, investigations were carried out on the modulation of the IL-33/ST2 axis by IL-17.Myofibroblasts isolated from intestinal biopsies/surgical samples from adult patients (UC n=3, CD n=4) and healthy donors (HC n=1) were found to secrete IL-6 and IL-8 (detected by ELISA) when stimulated for 24 hours with recombinant human IL-17A, IL-17F or IL-17AF (1ng/ml) (combined with 1ng/ml TNF or medium). Moreover, increased expression of IL-33 and ST2 was detected in myofibroblasts exposed to similar conditions (qPCR and confocal microscopy).Further analysis of myofibroblasts stimulated with IL-17 dimmers revealed no secretion of IL-6 or IL-8, however IL-17A+TNF diminished cytokine production compared with TNF on its own (p