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* = Presenting author

P044 Roles of IL-33 on murine colitis and M2 macrophage differentiation in inflammatory bowel diseases

D. H. Seo*1, 2, M. S. Kawk1, X. Che1, 2, H. W. Ma1, 2, J. H. Kim1, 2, D. H. Kim1, T. I. Kim1, W. H. Kim1, S. W. Kim1, 2, 3, J. H. Cheon1, 2, 3

1Yonsei University, Department of Internal Medicine and Institute of Gastroenterology, College of Medicine, Seoul, South Korea, 2Yonsei University, Brain Korea 21 PLUS Project for Medical Science, College of Medicine, Seoul, South Korea, 3Yonsei University, Severance Biomedical Science Institute, College of Medicine, Seoul, South Korea

Background

IL-33 is a member of the IL-1 cytokine superfamily that signals through ST2 receptor, and induces helper T-cell type 2 immune response. Type 2 immune response by Th2/Treg may differentiate monocytes into M2 type macrophages. Type 2 cytokines induced by M2 type macrophages have anti-inflammatory and epithelial wound-healing functions. However, the role and underlying mechanisms of IL-33 in IBD remain poorly understood. Accordingly, we sought to clarify the role and underlying mechanisms of IL-33 on course of ulcerative colitis (UC), Crohn’s disease (CD), and intestinal inflammatory bowel disease (IBD).

Methods

First, we evaluated the serum concentrations of IL-33 and sST2 in 45 healthy individuals and 206 patients with UC, CD, and IBD who were diagnosed at Severance Hospital, Seoul, Korea. Next, we assessed the effects and mechanisms of IL-33 on the tri-nitrobenzene sulfonic acid (TNBS)-induced experimental colitis that mimics human IBD. Finally, wound-healing function was assessed using HT-29 cells, and M2 macrophage differentiation was evaluated using RAW cells and PBMCs of health controls and IBD patients.

Results

The plasma levels of IL-33 were significantly decreased in UC and intestinal BD patients (UC, p = 0.003; IBD, p = 0.001), whereas the plasma levels of sST2 were significantly increased in UC and intestinal BD patients (UC, p < 0.001; IBD, p = 0.004). IL-33 mRNA levels were increased in the TNBS-treated mice, whereas recombinant mouse IL-33 (rmIL-33) administration substantially ameliorated TNBS-mediated colonic tissue injury and clinical symptoms of colitis. Additionally, degree of wound healing was significantly faster in IL-33 treated PBMCs in both healthy controls and IBD patients. Moreover, when we co-cultured human monocytes and lymphocytes with the treatment of recombinant human IL-33 (rhIL-33) for 24 hours, we found more intensified CD206 fluorescence, an M2 macrophage surface marker, than untreated group

Conclusion

Our data provide clear evidence that IL-33 plays a protective role in TNBS-induced colitis and epithelial wound healing, which was closely related to a Th1-to-Th2/Treg switch. Thus, IL-33 might a promising candidate for new treatments for IBD.