title: Interleukin-33 regulates intestinal inflammation by modulating macrophages in inflammatory bowel disease.
abstract: Interleukin 33 (IL-33) that signals through the ST2 receptor has emerged as a critical modulator in several inflammatory disorders, including inflammatory bowel disease (IBD). However, the precise mechanisms by which IL-33 modulates IBD are controversial. The aim of this study was thus to clarify the role of IL-33 in IBD. The plasma levels of IL-33 were significantly decreased, but soluble ST2 levels were increased in patients with IBD compared to healthy individuals. Moreover, IL-33 restored goblet cell numbers and induced macrophage switching from the M1 to the M2 phenotype. These effects were sufficient to ameliorate colitis in dextran sodium sulfate, trinitrobenzene sulfonic acid, and peritoneal cavity cell transfer models. IL-33 facilitated goblet cell restoration via modulating macrophages toward the M2 phenotype. In addition, wound healing was significantly faster in IL-33-treated human monocyte-derived macrophages than in control cells, which could be attributed to increased polarisation into M2 macrophages. We found that patients with IBD show decreased serum levels of IL-33 compared with healthy individuals and that IL-33 can attenuate colitis and aid tissue repair in mice. The mechanism by which IL-33 exerts these effects appears to involve the stimulation of differentiation of goblet cells and M2 macrophages.
authors.affiliation: Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.|Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Dong Hyuk
authors.initials: DH
authors.lastname: Seo
authors.affiliation: Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.|Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Che
authors.affiliation: Department of Internal Medicine, Graduate School, Yonsei University College of Medicine, Seoul, Korea.|Department of Internal Medicine, Kyung Hee University Hospital at Gang Dong, Kyung Hee University School of Medicine, Seoul, Korea.
authors.forename: Min Seob
authors.initials: MS
authors.lastname: Kwak
authors.affiliation: Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.|Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Soochan
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jae Hyeon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hyun Woo
authors.initials: HW
authors.lastname: Ma
authors.affiliation: Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.|Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Da Hye
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Tae Il
authors.initials: TI
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Won Ho
authors.initials: WH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea. swk21c@hanmail.net.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. swk21c@hanmail.net.|Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea. swk21c@hanmail.net.
authors.forename: Seung Won
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea. GENIUSHEE@yuhs.ac.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. GENIUSHEE@yuhs.ac.|Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea. GENIUSHEE@yuhs.ac.
authors.forename: Jae Hee
authors.initials: JH
authors.lastname: Cheon
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D020397:Goblet Cells / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000378:metabolism*; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000378:metabolism; D000067596:Interleukin-33 / Q000097:blood* / Q000494:pharmacology / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000473:pathology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D000893:Anti-Inflammatory Agents; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33