Cited by 252T-cell and B-cell ImmunologyGut microbiota and healthImmune Response and Inflammation

A commensal symbiotic factor derived from Bacteroides fragilis promotes human CD39 + Foxp3 + T cells and T reg function

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Telesford, Kiel M, Yan, Wang, Ochoa-Reparaz, Javier, Pant, Anudeep, Kircher, Christopher, Christy, Marc A, Begum-Haque, Sakhina, Kasper, Dennis L +1 more·2015·Gut Microbes

Abstract

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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Crossref · 10.1080/19490976.2015.1056973

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  • PSA exposure increases ENTPD1 expression on FoxP3+ Tregs, suggesting a potential intersection between PSA and extracellular ATP in immune regulation.

    “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).”

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  1. Schuler PJ, Schilling B, Harasymczuk M, Hoffmann TK, Johnson J, Lang S, Whiteside TL. Phenotypic and functional characteristics of CD4CCD39C FOXP3C and CD4CCD39CFOXP3neg T-cell subsets in cancer patients. Eur J Immunol 2012; 42:1876-85:n/a-n/a; PMID:22585562

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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
Published
2015-07-04
Volume
6
Issue
4
Pages
234-242
ISSN
  • 1949-0976 (ISSN-L)
  • 1949-0984
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
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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