Dysregulated Circulating Dendritic Cell Function in Ulcerative Colitis Is Partially Restored by Probiotic Strain Lactobacillus casei Shirota

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....

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Main Authors: 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
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2013/573576
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author 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
author_facet 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
author_sort Elizabeth R. Mann
collection DOAJ
description 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.
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spelling doaj-art-bd54172861994b7ebf1f44fceab9a3ab2025-02-03T05:44:07ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/573576573576Dysregulated Circulating Dendritic Cell Function in Ulcerative Colitis Is Partially Restored by Probiotic Strain Lactobacillus casei ShirotaElizabeth R. Mann0Jialu You1Verena Horneffer-van der Sluis2David Bernardo3Hafid Omar Al-Hassi4Jon Landy5Simon T. Peake6Linda V. Thomas7Cheng T. Tee8Gui Han Lee9Ailsa L. Hart10Parveen Yaqoob11Stella C. Knight12Antigen Presentation Research Group, Imperial College London, Northwick Park and St. Mark’s Campus, Level 7W St. Mark’s Hospital, Watford Road, Harrow HA1 3UJ, UKDepartment of Food and Nutritional Sciences, University of Reading, Reading, UKNorthwick Park Institute for Medical Research, Harrow, UKAntigen Presentation Research Group, Imperial College London, Northwick Park and St. Mark’s Campus, Level 7W St. Mark’s Hospital, Watford Road, Harrow HA1 3UJ, UKAntigen Presentation Research Group, Imperial College London, Northwick Park and St. Mark’s Campus, Level 7W St. Mark’s Hospital, Watford Road, Harrow HA1 3UJ, UKAntigen Presentation Research Group, Imperial College London, Northwick Park and St. Mark’s Campus, Level 7W St. Mark’s Hospital, Watford Road, Harrow HA1 3UJ, UKAntigen Presentation Research Group, Imperial College London, Northwick Park and St. Mark’s Campus, Level 7W St. Mark’s Hospital, Watford Road, Harrow HA1 3UJ, UKYakult UK Ltd., West End Road, South Ruislip, UKAntigen Presentation Research Group, Imperial College London, Northwick Park and St. Mark’s Campus, Level 7W St. Mark’s Hospital, Watford Road, Harrow HA1 3UJ, UKAntigen Presentation Research Group, Imperial College London, Northwick Park and St. Mark’s Campus, Level 7W St. Mark’s Hospital, Watford Road, Harrow HA1 3UJ, UKAntigen Presentation Research Group, Imperial College London, Northwick Park and St. Mark’s Campus, Level 7W St. Mark’s Hospital, Watford Road, Harrow HA1 3UJ, UKDepartment of Food and Nutritional Sciences, University of Reading, Reading, UKAntigen Presentation Research Group, Imperial College London, Northwick Park and St. Mark’s Campus, Level 7W St. Mark’s Hospital, Watford Road, Harrow HA1 3UJ, UKBackground. 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.http://dx.doi.org/10.1155/2013/573576
spellingShingle 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
Dysregulated Circulating Dendritic Cell Function in Ulcerative Colitis Is Partially Restored by Probiotic Strain Lactobacillus casei Shirota
Mediators of Inflammation
title Dysregulated Circulating Dendritic Cell Function in Ulcerative Colitis Is Partially Restored by Probiotic Strain Lactobacillus casei Shirota
title_full Dysregulated Circulating Dendritic Cell Function in Ulcerative Colitis Is Partially Restored by Probiotic Strain Lactobacillus casei Shirota
title_fullStr Dysregulated Circulating Dendritic Cell Function in Ulcerative Colitis Is Partially Restored by Probiotic Strain Lactobacillus casei Shirota
title_full_unstemmed Dysregulated Circulating Dendritic Cell Function in Ulcerative Colitis Is Partially Restored by Probiotic Strain Lactobacillus casei Shirota
title_short Dysregulated Circulating Dendritic Cell Function in Ulcerative Colitis Is Partially Restored by Probiotic Strain Lactobacillus casei Shirota
title_sort dysregulated circulating dendritic cell function in ulcerative colitis is partially restored by probiotic strain lactobacillus casei shirota
url http://dx.doi.org/10.1155/2013/573576
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