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A commensal symbiotic factor derived from Bacteroides fragilis promotes human CD39 + Foxp3 + T cells and T reg function
Open accessAbstract
Polysaccharide A (PSA) derived from the human commensal Bacteroides fragilis is a symbiosis factor that stimulates immunologic development within mammalian hosts. PSA rebalances skewed systemic T helper responses and promotes T regulatory cells (Tregs). However, PSA-mediated induction of Foxp3 in humans has not been reported. In mice, PSA-generated Foxp3(+) Tregs dampen Th17 activity thereby facilitating bacterial intestinal colonization while the increased presence and function of these regulatory cells may guard against pathological organ-specific inflammation in hosts. We herein demonstrate that PSA induces expression of Foxp3 along with CD39 among naïve CD4 T cells in vitro while promoting IL-10 secretion. PSA-activated dendritic cells are essential for the mediation of this regulatory response. When cultured with isolated Foxp3(+) Tregs, PSA enriched Foxp3 expression, enhanced the frequency of CD39(+)HLA-DR(+) cells, and increased suppressive function as measured by decreased TNFα expression by LPS-stimulated monocytes. Our findings are the first to demonstrate in vitro induction of human CD4(+)Foxp3(+) T cells and enhanced suppressive function of circulating Foxp3(+) Tregs by a human commensal bacterial symbiotic factor. Use of PSA for the treatment of human autoimmune diseases, in particular multiple sclerosis and inflammatory bowel disease, may represent a new paradigm in the approach to treating autoimmune disease.
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“PSA exposure increases expression of ENTPD1 on FoxP3+ Tregs, thus suggesting a potential intersection between PSA and (microbially derived) extracellular ATP in the regulation of the immune system (Telesford et al., 2015).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Telesford et al., 2015
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Metadata
- Authors
- Telesford, K. M., Yan, W., Ochoa-Reparaz, J., Pant, A., Kircher, C., Christy, M. A., Begum-Haque, S., Kasper, D. L., & Kasper, L. H.
- Affiliations
- Dartmouth College (US)
- Harvard University (US)
- Corresponding author
- Telesford, Kiel M
- Venue
- Gut Microbes
- Publisher
- Informa UK Limited
- Published
- 2015-07-04
- Volume
- 6
- Issue
- 4
- Pages
- 234-242
- ISSN
- 1949-0976 (ISSN-L)
- 1949-0984
- PMC
- PMC4615798
- OpenAlex
- W1894807755
- Cited by
- 252
- References
- 51
- Citations by year
- 2026: 14 · 2025: 30 · 2024: 22 · 2023: 26 · 2022: 28 · 2021: 27 · 2020: 20 · 2019: 21 · 2018: 20 · 2017: 22 · 2016: 22
- FWCI
- 10.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gut Microbes (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Multiple Sclerosis Society
- Multiple Sclerosis Society
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R41AI110170)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- Bacteroides fragilis, polysaccharide A, regulatory T cells, Foxp3, CD39, commensal bacteria, gut microbiota, dendritic cells, IL-10, Treg suppressive function, autoimmune disease, multiple sclerosis, inflammatory bowel disease, Th17 cells
- MeSH terms
- Apyrase, Bacteroides fragilis, Cells, Cultured, Dendritic Cells, Humans, Lipopolysaccharides, Symbiosis, CD4-Positive T-Lymphocytes, Antigens, CD, Immunophenotyping, T-Lymphocyte Subsets, Forkhead Transcription Factors
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