Generation of regulatory dendritic cells and CD4+Foxp3+ T cells by probiotics administration suppresses immune disorders.
The beneficial effects of probiotics have been described in many diseases, but the mechanism by which they modulate the immune system is poorly understood. In this study, we identified a mixture of probiotics that up-regulates CD4(+)Foxp3(+) regulatory T cells (Tregs). Administration of the probiotics mixture induced both T-cell and B-cell hyporesponsiveness and down-regulated T helper (Th) 1, Th2, and Th17 cytokines without apoptosis induction. It also induced generation of CD4(+)Foxp3(+) Tregs from the CD4(+)CD25(-) population and increased the suppressor activity of naturally occurring CD4(+)CD25(+) Tregs. Conversion of T cells into Foxp3(+) Tregs is directly mediated by regulatory dendritic cells (rDCs) that express high levels of IL-10, TGF-beta, COX-2, and indoleamine 2,3-dioxygenase. Administration of probiotics had therapeutical effects in experimental inflammatory bowel disease, atopic dermatitis, and rheumatoid arthritis. The therapeutical effect of the probiotics is associated with enrichment of CD4(+)Foxp3(+) Tregs in the inflamed regions. Collectively, the administration of probiotics that enhance the generation of rDCs and Tregs represents an applicable treatment of inflammatory immune disorders.
Kwon
Ho-Keun
HK
Department of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea.
Lee
Choong-Gu
CG
So
Jae-Seon
JS
Chae
Chang-Suk
CS
Hwang
Ji-Sun
JS
Sahoo
Anupama
A
Nam
Jong Hee
JH
Rhee
Joon Haeng
JH
Hwang
Ki-Chul
KC
Im
Sin-Hyeog
SH
D019264:Adoptive Transfer; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy; D039521:CD11c Antigen / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D003876:Dermatitis, Atopic / Q000276:immunology / Q000473:pathology / Q000628:therapy; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D007154:Immune System Diseases / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D007165:Immunosuppression Therapy; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000473:pathology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D019936:Probiotics / Q000008:administration & dosage*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D039521:CD11c Antigen; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse