Dysregulated circulating dendritic cell function in ulcerative colitis is partially restored by probiotic strain Lactobacillus casei Shirota

Elizabeth R Mann, Jialu You, Verena Horneffer-van der Sluis, David Bernardo, Hafid Omar Al-Hassi, Jon Landy, Simon T Peake, Linda V Thomas, Cheng T Tee, Gui Han Lee, Ailsa L Hart, Parveen Yaqoob, Stella C Knight

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Dendritic cells regulate immune responses to microbial products and play a key role in ulcerative colitis (UC) pathology. We determined the immunomodulatory effects of probiotic strain Lactobacillus casei Shirota (LcS) on human DC from healthy controls and active UC patients.

METHODS: Human blood DC from healthy controls (control-DC) and UC patients (UC-DC) were conditioned with heat-killed LcS and used to stimulate allogeneic T cells in a 5-day mixed leucocyte reaction.

RESULTS: UC-DC displayed a reduced stimulatory capacity for T cells (P < 0.05) and enhanced expression of skin-homing markers CLA and CCR4 on stimulated T cells (P < 0.05) that were negative for gut-homing marker β7. LcS treatment restored the stimulatory capacity of UC-DC, reflecting that of control-DC. LcS treatment conditioned control-DC to induce CLA on T cells in conjunction with β7, generating a multihoming profile, but had no effects on UC-DC. Finally, LcS treatment enhanced DC ability to induce TGFβ production by T cells in controls but not UC patients.

CONCLUSIONS: We demonstrate a systemic, dysregulated DC function in UC that may account for the propensity of UC patients to develop cutaneous manifestations. LcS has multifunctional immunoregulatory activities depending on the inflammatory state; therapeutic effects reported in UC may be due to promotion of homeostasis.

Original languageEnglish
Article number573576
Number of pages12
JournalMediators of Inflammation
Volume2013
DOIs
Publication statusPublished - 2013

Keywords

  • Cell Proliferation
  • Cells, Cultured
  • Colitis, Ulcerative/immunology
  • Cytokines/metabolism
  • Dendritic Cells/cytology
  • Flow Cytometry
  • Homeostasis
  • Humans
  • Inflammation/immunology
  • Lactobacillus casei/immunology
  • Lymphocyte Activation
  • Probiotics/pharmacology
  • T-Lymphocytes/cytology
  • Transforming Growth Factor beta/metabolism

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