title: Differential accumulation and function of proinflammatory 6-sulfo LacNAc dendritic cells in lymph node and colon of Crohn's versus ulcerative colitis patients.
abstract: Human Slan DCs have been studied in patients with psoriasis, rheumatoid arthritis, cancer, and autoimmune diseases. In this study, we investigated the frequency, phenotype, and function of Slan DCs in blood, colon, as well as mLNs of patients with IBD. We first show that the frequency of circulating CD14(dull)Slan DCs was reduced in CD patients refractory to immunosuppressive drugs or TNF-α blockers relative to untreated CD, UC, and healthy subjects. In blood of CD patients, Slan DCs expressed CD172a, as detected by CD47 fusion protein binding, when compared with its lack of expression in control subjects. Next, we demonstrate that CD172a(+)Slan DCs that produced IL-1β and TNF-α accumulated in mLNs and colons of CD patients. The CD172a(+)Slan DCs up-regulated their expression of CD14 in CD tissues and the proinflammatory cytokines were produced in CD14(bright)CD172a(+)Slan DCs. By contrast, no difference was noted in the frequency of Slan DCs between inflamed, noninflamed colonic mucosa of UC patients and control, non-IBD donors. Finally, the percentage of cytokine-producing Slan DCs also augmented in response to TLR2 and NOD2 in in vitro stimulation in PBMCs of CD, but not UC, patients. In conclusion, we propose that proinflammatory CD14(bright)CD172a(+)Slan DCs are a distinguishing feature between CD and UC, as these cells accumulate uniquely in mLNs and colonic mucosa of CD patients. Thus, Slan DCs may contribute to CD immunopathogenesis.
authors.affiliation: *Immunoregulation Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada; Center for Innovative and Translational Medicine, Kochi University Medical School, Kochi, Japan; and Departments of Gastroenterology, Digestive Tract Surgery, and Pathology, Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada.
authors.forename: Marwa
authors.initials: M
authors.lastname: Bsat
authors.affiliation: *Immunoregulation Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada; Center for Innovative and Translational Medicine, Kochi University Medical School, Kochi, Japan; and Departments of Gastroenterology, Digestive Tract Surgery, and Pathology, Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada.
authors.forename: Laurence
authors.initials: L
authors.lastname: Chapuy
authors.affiliation: *Immunoregulation Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada; Center for Innovative and Translational Medicine, Kochi University Medical School, Kochi, Japan; and Departments of Gastroenterology, Digestive Tract Surgery, and Pathology, Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada.
authors.forename: Nobuyasu
authors.initials: N
authors.lastname: Baba
authors.affiliation: *Immunoregulation Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada; Center for Innovative and Translational Medicine, Kochi University Medical School, Kochi, Japan; and Departments of Gastroenterology, Digestive Tract Surgery, and Pathology, Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada.
authors.forename: Manuel
authors.initials: M
authors.lastname: Rubio
authors.affiliation: *Immunoregulation Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada; Center for Innovative and Translational Medicine, Kochi University Medical School, Kochi, Japan; and Departments of Gastroenterology, Digestive Tract Surgery, and Pathology, Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada.
authors.forename: Benoit
authors.initials: B
authors.lastname: Panzini
authors.affiliation: *Immunoregulation Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada; Center for Innovative and Translational Medicine, Kochi University Medical School, Kochi, Japan; and Departments of Gastroenterology, Digestive Tract Surgery, and Pathology, Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada.
authors.forename: Ramses
authors.initials: R
authors.lastname: Wassef
authors.affiliation: *Immunoregulation Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada; Center for Innovative and Translational Medicine, Kochi University Medical School, Kochi, Japan; and Departments of Gastroenterology, Digestive Tract Surgery, and Pathology, Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada.
authors.forename: Carole
authors.initials: C
authors.lastname: Richard
authors.affiliation: *Immunoregulation Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada; Center for Innovative and Translational Medicine, Kochi University Medical School, Kochi, Japan; and Departments of Gastroenterology, Digestive Tract Surgery, and Pathology, Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada.
authors.forename: Genevieve
authors.initials: G
authors.lastname: Soucy
authors.affiliation: *Immunoregulation Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada; Center for Innovative and Translational Medicine, Kochi University Medical School, Kochi, Japan; and Departments of Gastroenterology, Digestive Tract Surgery, and Pathology, Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada.
authors.forename: Heena
authors.initials: H
authors.lastname: Mehta
authors.affiliation: *Immunoregulation Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada; Center for Innovative and Translational Medicine, Kochi University Medical School, Kochi, Japan; and Departments of Gastroenterology, Digestive Tract Surgery, and Pathology, Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada m.sarfati@umontreal.ca.
authors.forename: Marika
authors.initials: M
authors.lastname: Sarfati
mesh_terms: D000328:Adult; D000368:Aged; D000606:Amino Sugars / Q000096:biosynthesis / Q000276:immunology; D003093:Colitis, Ulcerative / Q000276:immunology*; D003106:Colon / Q000276:immunology*; D003424:Crohn Disease / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: C467438:6-sulfo-LacNac; D000606:Amino Sugars; D016207:Cytokines
keywords: CD172; CD47; cytokines; human; inflammatory bowel diseases