Probiotics ameliorate recurrent Th1-mediated murine colitis by inducing IL-10 and IL-10-dependent TGF-beta-bearing regulatory cells.
Recent studies of murine models of mucosal inflammation suggest that, whereas some kinds of bacterial microflora are inducers of disease, others, known as probiotics, prevent disease. In the present study, we analyzed the regulatory cytokine and cell response to probiotic (VSL#3) administration in the context of the Th1 T cell colitis induced by trinitrobenzene sulfonic acid treatment of SJL/J mice. Daily administration of probiotics for 3 wk to mice during a remission period between a first and second course of colitis induced by trinitrobenzene sulfonic acid, resulted in a milder form of recurrent colitis than observed in mice administered PBS during this same period. This protective effect was attributable to effects on the lamina propria mononuclear cell (LPMC) population, because it could be transferred by LPMC from probiotic-treated mice to naive mice. Probiotic administration was associated with an early increase in the production of IL-10 and an increased number of regulatory CD4+ T cells bearing surface TGF-beta in the form of latency-associated protein (LAP) (LAP+ T cells). The latter were dependent on the IL-10 production because administration of anti-IL-10R mAb blocked their appearance. Finally, the LAP+ T cells were essential to the protective effect of probiotics because administration of anti-IL-10R or anti-TGF-beta at the initiation of recurrent colitis induction or depletion of LAP+ T cells from LPMC abolished the latter's capacity to transfer protection to naive recipients. These studies show that probiotic (VSL#3) administration during a remission period ameliorates the severity of recurrent colitis by inducing an immunoregulatory response involving TGF-beta-bearing regulatory cells.
Di Giacinto
Claudia
C
Immune-Mediated Diseases Section, Department of Infectious, Parasitic, and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
Marinaro
Mariarosaria
M
Sanchez
Massimo
M
Strober
Warren
W
Boirivant
Monica
M
D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D016753:Interleukin-10 / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D010446:Peptide Fragments / Q000378:metabolism; D019936:Probiotics; D011498:Protein Precursors / Q000378:metabolism; D012008:Recurrence; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
D010446:Peptide Fragments; D011498:Protein Precursors; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D014302:Trinitrobenzenesulfonic Acid