Dysregulated Circulating Dendritic Cell Function in Ulcerative Colitis Is Partially Restored by Probiotic StrainLactobacillus caseiShirota

[摘要] Background. Dendritic cells regulate immune responses to microbial products and play a key roleinulcerativecolitis (UC)pathology. We determined the immunomodulatory effects of probiotic strainLactobacillus caseiShirota (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 markerβ7. LcS treatment restored the stimulatorycapacityofUC-DC, reflectingthatofcontrol-DC.LcStreatment conditioned control-DC to induce CLA on T cells in conjunction withβ7, generating a multihoming profile, but had no effects on UC-DC. Finally, LcS treatment enhanced DC ability to induce TGFβproduction 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.

[学科分类] 生理学与病理学