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 m...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2010-02, Vol.107 (5), p.2159-2164
Main Authors: Kwon, Ho-Keun, Lee, Choong-Gu, So, Jae-Seon, Chae, Chang-Suk, Hwang, Ji-Sun, Sahoo, Anupama, Nam, Jong Hee, Rhee, Joon Haeng, Hwang, Ki-Chul, Im, Sin-Hyeog
Format: Article
Language:English
Subjects:
Adoptive Transfer
Animals
Arthritis, Experimental - immunology
Arthritis, Experimental - pathology
Arthritis, Experimental - therapy
Autoimmune diseases
B lymphocytes
Biological Sciences
CD11c Antigen - metabolism
Cytokines
Dendritic cells
Dendritic Cells - immunology
Dendritic Cells - pathology
Dermatitis, Atopic - immunology
Dermatitis, Atopic - pathology
Dermatitis, Atopic - therapy
Disease Models, Animal
Drug regulation
Effects
Forkhead Transcription Factors - metabolism
Immune disorders
Immune system
Immune System Diseases - immunology
Immune System Diseases - pathology
Immune System Diseases - therapy
Immunosuppression
Inflammatory bowel diseases
Inflammatory Bowel Diseases - immunology
Inflammatory Bowel Diseases - pathology
Inflammatory Bowel Diseases - therapy
Medical treatment
Mice
Mice, Inbred BALB C
Mice, Transgenic
Population growth
Probiotics
Probiotics - administration & dosage
T cell receptors
T lymphocytes
T-Lymphocytes, Regulatory - immunology
T-Lymphocytes, Regulatory - metabolism
T-Lymphocytes, Regulatory - pathology
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Summary: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-β, 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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0904055107