title: Dysregulated circulating dendritic cell function in ulcerative colitis is partially restored by probiotic strain Lactobacillus casei Shirota.
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.
authors: Antigen Presentation Research Group, Imperial College London, Northwick Park and St. Mark's Campus, Level 7W St. Mark's Hospital, Watford Road, Harrow HA1 3UJ, UK.
authors: Elizabeth R
authors: ER
authors: Mann
authors: Jialu
authors: J
authors: You
authors: Verena
authors: V
authors: Horneffer-van der Sluis
authors: David
authors: D
authors: Bernardo
authors: Hafid
authors: H
authors: Omar Al-Hassi
authors: Jon
authors: J
authors: Landy
authors: Simon T
authors: ST
authors: Peake
authors: Linda V
authors: LV
authors: Thomas
authors: Cheng T
authors: CT
authors: Tee
authors: Gui Han
authors: GH
authors: Lee
authors: Ailsa L
authors: AL
authors: Hart
authors: Parveen
authors: P
authors: Yaqoob
authors: Stella C
authors: SC
authors: Knight
mesh_terms: D049109:Cell Proliferation; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000276:immunology* / Q000382:microbiology*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D005434:Flow Cytometry; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007780:Lacticaseibacillus casei / Q000276:immunology*; D008213:Lymphocyte Activation; D019936:Probiotics / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D016207:Cytokines; D016212:Transforming Growth Factor beta
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