Ees Nieuwenhuis

Chemokine production by buccal epithelium as a distinctive feature of pediatric Crohn disease

Objectives: Inflammatory bowel diseases (IBD) represent an aberrant immune response by the mucosal immune system to luminal bacteria. Because the oral mucosa harbors the first epithelial cells that interact with microorganisms, we assessed the immunologic activity of buccal epithelium in children with IBD and adults with Crohn disease. Methods: Buccal epithelial cells were obtained from 17 children and 14 adults with Crohn disease, 18 children with ulcerative colitis, and 40 controls. Cells were cultured with and without microbial stimulation. Chemokine levels were determined in culture supernatants by cytometric bead array and enzyme-linked immunoabsorbent assay. CXCL-8 production was studied by immunohistochemical analysis of these cells. CXCL-8 production by lipopolysaccharide stimulated monocyte-derived dendritic cells from these patients was determined. Results: Compared with controls, pediatric ulcerative colitis patients, and adult Crohn disease patients, only in children with Crohn disease did buccal epithelial cells exhibit enhanced production of CXCL-8, CXCL-9, and CXCL-10. In vitro stimulation with lipopolysaccharide or zymosan resulted in a further increase of chemokine levels only in cells from pediatric Crohn disease patients. CXCL-8 production by stimulated monocyte-derived dendritic cells from children with Crohn disease was equal to that of children with ulcerative colitis. Conclusions: Buccal epithelium of children with Crohn disease is immunologically active, even in the absence of oral lesions. The enhanced chemokine production is associated with pediatric Crohn disease and appears restricted to cells derived from the epithelial barrier. Assessment of chemokine production by buccal epithelial cells may become a new, rapid, noninvasive test for screening and classification of IBD in children.

Production of IL12p70 and IL23 by monocyte-derived dendritic cells in children with inflammatory bowel disease

Inflammatory bowel disease (IBD) patients represent a heterogeneous group of patients that may need novel classification beyond just Crohns’ disease (CD) and ulcerative colitis (UC). Notably, based on patient specifics such as genetics, disease location, immune responses and drug responsiveness, it seems likely that early-onset IBDs represents a specific disease entity.1 Consequently, various disease-associated effector T cells have been identified, probably generated under the control of cytokines that are produced by antigen-presenting cells. In their recent publication, Kugathsan et al demonstrated that the level of IL12β2 (interleukin 12 receptor) expression by mucosal T cells may be a major determinant during the initial manifestations of CD for the development of the typically associated mucosal Th1 cytokine profile.2 In this case, the presence of a specific T cell receptor correlated …

O-04: Secretory leukocyte protease inhibitor (SLPI) is a potent regulator of microbial induced monocyte activation and intestinal inflammation

O-01 IL-10 receptor dependent signals regulate the generation and function of anti-inflammatory macrophages in mice and humans S.B. Snapper1 *, D. Shouval1, A. Biswas1, J.A. Goettel1, K. McCann1, J.C. Escher2, J.N. Samsom2, R.S. Somech3, B. Weiss3, R. Beier4, L. Conklin5, C.L. Ebens6, F.G.M. Santos7, M. Sherlock8, C. Klein9, A.M. Muise10, B.H. Horwitz11. 1Boston Children’s Hospital, Boston, United States of America, 2Erasmus Medical Center Sophia Children’s Hospital, Rotterdam, The Netherlands, 3Edmond and Lily Safra Children’s Hospital, Tel Hashomer, Israel, 4Hannover Medical School, Hannover, Germany, 5Children’s National Medical Center, Washington DC, United States of America, 6University of Michigan, Ann Arbor, United States of America, 7Hospital das Clinicas, Federal University of Minas Gerais, Minas Gerais, Brazil, 8McMaster Children’s Hospital, West Hamilton, Canada, 9Dr von Hauner Children’s Hospital, Munich, Germany, 10Hospital for Sick Children, Toronto, Canada, 11Harvard Medical School, Boston, United States of America