title: Altered human gut dendritic cell properties in ulcerative colitis are reversed by Lactobacillus plantarum extracellular encrypted peptide STp.
abstract: METHODS
  The human/microbiota cross-talk is partially mediated by bacteria-derived peptides like Serine-Threonine peptide (STp), which is resistant to gut proteolysis, is found in the human healthy colon and induces regulatory properties on gut dendritic cells (DCs); here we characterized human gut DC in ulcerative colitis (UC) patients and studied the effect of STp on their properties.
  
  
  RESULTS
  Human colonic DC from healthy controls and UC patients were isolated, conditioned for 24 h +/- STp and characterized by flow cytometry, immunohistochemistry, and electron microscopy. Expression of immature DC markers DC-SIGN and ILT3, and Toll-like receptors were increased on gut UC-DC. Langerin (involved in phagocytosis), lymph node homing marker CCR7, and activation markers CD40/CD80/CD86 were decreased in UC. Gut DC had restricted stimulatory capacity for T-cells in UC. Conditioning of DC with STp in vitro reduced Toll-like receptor expression, increased CD40 and CD80 expression, and restored their stimulatory capacity.
  
  
  CONCLUSIONS
  Colonic DCs display an abnormal immature phenotype in UC, which was partially restored following STp treatment. Bacteria-derived metabolites, like STp, seem to have a role in gut homeostasis that is missing in UC so they might lead a new era of probiotic products setting the basis for nondrug dietary therapy in inflammatory bowel disease.
authors.affiliation: Antigen Presentation Research Group, Imperial College London, Northwick Park and St. Mark's Campus, Harrow, UK.
authors.forename: Hafid O
authors.initials: HO
authors.lastname: Al-Hassi
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Mann
authors.forename: Borja
authors.initials: B
authors.lastname: Sanchez
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: English
authors.forename: Simon T C
authors.initials: ST
authors.lastname: Peake
authors.forename: Jonathan
authors.initials: J
authors.lastname: Landy
authors.forename: Ripple
authors.initials: R
authors.lastname: Man
authors.forename: Maria
authors.initials: M
authors.lastname: Urdaci
authors.forename: Ailsa L
authors.initials: AL
authors.lastname: Hart
authors.forename: Luis
authors.initials: L
authors.lastname: Fernandez-Salazar
authors.forename: Gui Han
authors.initials: GH
authors.lastname: Lee
authors.forename: Jose A
authors.initials: JA
authors.lastname: Garrote
authors.forename: Eduardo
authors.initials: E
authors.lastname: Arranz
authors.forename: Abelardo
authors.initials: A
authors.lastname: Margolles
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Stagg
authors.forename: Stella C
authors.initials: SC
authors.lastname: Knight
authors.forename: David
authors.initials: D
authors.lastname: Bernardo
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003093:Colitis, Ulcerative / Q000382:microbiology / Q000628:therapy*; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D064368:Healthy Volunteers; D006801:Humans; D007150:Immunohistochemistry; D015212:Inflammatory Bowel Diseases / Q000473:pathology / Q000628:therapy; D048191:Lactiplantibacillus plantarum / Q000378:metabolism*; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D008297:Male; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins; D008875:Middle Aged; D010455:Peptides / Q000494:pharmacology*; D019936:Probiotics / Q000008:administration & dosage; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic; D012694:Serine / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000378:metabolism; D013912:Threonine / Q000494:pharmacology*; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D019013:CD40 Antigens; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins; D010455:Peptides; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D012694:Serine; D013912:Threonine; D051193:Toll-Like Receptors; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C121916:CD207 protein, human; C107907:LILRB4 protein, human
keywords: Dendritic Cells; Microbiota; Postbiotics; STp; Ulcerative colitis