Inflammatory Bowel Disease-Associated Interleukin-33 Is Preferentially Expressed in Ulceration-Associated Myofibroblasts

Interleukin 33 (IL 33) is a novel member of the inter leukin 1 family that induces mucosal pathology in vivo and may drive fibrosis development and angio genesis To address its potential role in inflammatory bowel disease we explored its tissue expression in biopsy specimens from untreated ulcerative colitis patients, observing a 2 6 fold up regulation of 11, 33 mRNA levels compared to controls Immunohistochemical analyses of surgical specimens showed that a prominent source of IL 33 in ulcerative colitis lesions were ulceration associated myofibroblasts that co expressed the fibroblast marker heat shock pro tern 47 platelet derived growth factor receptor (PDGFR)beta and in part, the myofibroblast marker a smooth muscle actin (SMA) In contrast IL 33 positive myofibroblasts were almost absent near the deep fissures seen in Crohn s disease A screen of known and putative activators of 11 33 in cultured fibroblasts revealed that the Toll like receptor 3 agonist poly (I C) was among the strongest inducers of IL 33 and that it synergized with transforming growth factor beta a combination also known to boost myofibroblast differentiation Experimental wound healing in rat skin revealed that the de novo induction of IL-33 in pericytes and the possible activation of scattered tissue resident IL-33(+)PDGFR beta(+)alpha SMA(-) fibroblast like cells were early events that preceded the later appearance of IL 33(+)PDGFR beta(+)alpha SMA(+) cells In conclusion our data point to a novel role for IL-33 in mucosal healing and wound repair and to an interesting difference be tween ulcerative colitis and Crohn s disease (Am J Pathol 2010, 177 2804-2815 DOI 10.2353/ajpath 2010 100378)