Abstract
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. 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. 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.
Highlights
Ulcerative colitis (UC) results from inappropriate mucosal immune responses to constituents of the intestinal flora in genetically predisposed individuals [1]
We have analyzed the phenotype and function of human gut dendritic cells (DC) to demonstrate for the first time, to our knowledge, that in UC DC exhibit an immature phenotype with reduced langerin and chemokine receptor 7 (CCR7) expression, compared to healthy controls
We have previously demonstrated that serine-threonine peptide (STp), a peptide secreted from probiotic strain L. plantarum, is present in the colon of healthy controls and has regulatory effects on gut DC in vitro [22]
Summary
Ulcerative colitis (UC) results from inappropriate mucosal immune responses to constituents of the intestinal flora in genetically predisposed individuals [1]. Intestinal DCs are present within Peyer’s patches and distributed throughout the lamina propria (LP), and maintain the delicate balance in the gut between immunogenicity against invading pathogens and tolerance of the commensal microbiota Disruption of this balance can result in inflammatory bowel disease (IBD) [4, 5]. Upon DC activation lymph node homing marker C-chemokine receptor 7 (CCR7) is upregulated on DC enabling migration to secondary lymphoid tissue in order to generate primary T-cell responses [8] These T-cell responses generated can be immunogenic or tolerogenic [3,9], but properties of healthy gut DCs suggest that in the steady state, gut DCs have a homeostatic role, likely to be due to the high antigenic load including the gut microbiota and food antigens. Altered DC phenotype and function in UC suggests that they contribute to UC pathogenesis [5, 13, 14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
