Altered human gut dendritic cell properties in ulcerative colitis are reversed by Lactobacillus plantarum extracellular encrypted peptide STp

Mol Nutr Food Res. 2014 May;58(5):1132-43. doi: 10.1002/mnfr.201300596. Epub 2013 Dec 18.

Abstract

Scope: 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.

Methods and 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.

Conclusion: 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.

Keywords: Dendritic Cells; Microbiota; Postbiotics; STp; Ulcerative colitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • B7-1 Antigen / genetics
  • B7-1 Antigen / metabolism
  • CD40 Antigens / genetics
  • CD40 Antigens / metabolism
  • Case-Control Studies
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cell Proliferation / drug effects
  • Colitis, Ulcerative / microbiology
  • Colitis, Ulcerative / therapy*
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism*
  • Female
  • Gastrointestinal Tract / drug effects
  • Gastrointestinal Tract / metabolism
  • Gastrointestinal Tract / microbiology
  • Healthy Volunteers
  • Humans
  • Immunohistochemistry
  • Inflammatory Bowel Diseases / pathology
  • Inflammatory Bowel Diseases / therapy
  • Lactobacillus plantarum / metabolism*
  • Lectins, C-Type / genetics
  • Lectins, C-Type / metabolism
  • Male
  • Mannose-Binding Lectins / genetics
  • Mannose-Binding Lectins / metabolism
  • Membrane Glycoproteins
  • Middle Aged
  • Peptides / pharmacology*
  • Probiotics / administration & dosage
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Receptors, Immunologic
  • Serine / pharmacology*
  • T-Lymphocytes / metabolism
  • Threonine / pharmacology*
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / metabolism

Substances

  • Antigens, CD
  • B7-1 Antigen
  • CD207 protein, human
  • CD40 Antigens
  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • LILRB4 protein, human
  • Lectins, C-Type
  • Mannose-Binding Lectins
  • Membrane Glycoproteins
  • Peptides
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • Toll-Like Receptors
  • Threonine
  • Serine