The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation
Arpaia, N., Campbell, C., Fan, X., Dikiy, S., van der Veeken, J., deRoos, P., Liu, H., Cross, J. R., Pfeffer, K., Coffer, P. J., et al. (2013) · Nature · doi:10.1038/nature12726 · Cited by 4,838
Induction of Intestinal Th17 Cells by Segmented Filamentous Bacteria
Ivanov, I. I., Atarashi, K., Manel, N., Brodie, E. L., Shima, T., Karaoz, U., Wei, D., Goldfarb, K. C., Santee, C. A., Lynch, S. V., et al. (2009) · Cell · doi:10.1016/j.cell.2009.09.033 · Cited by 4,554
An Immunomodulatory Molecule of Symbiotic Bacteria Directs Maturation of the Host Immune System
Mazmanian, S. K., Liu, C. H., Tzianabos, A. O., & Kasper, D. L. (2005) · Cell · doi:10.1016/j.cell.2005.05.007 · Cited by 2,910
Self-citationCD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells
Liu, W., Putnam, A. L., Xu-yu, Z., Szot, G. L., Lee, M. R., Zhu, S., Gottlieb, P. A., Kapranov, P., Gingeras, T. R., de St. Groth, B. F., et al. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20060772 · Cited by 2,606
Round, J. L., & Mazmanian, S. K. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909122107 · Cited by 2,233
Louis, P., & Flint, H. J. (2009) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.2009.01514.x · Cited by 2,179
PD-L1 regulates the development, maintenance, and function of induced regulatory T cells
Francisco, L. M., Salinas, V. H., Brown, K. E., Vanguri, V. K., Freeman, G. J., Kuchroo, V. K., & Sharpe, A. H. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20090847 · Cited by 2,072
Machiels, K., Joossens, M., Sabino, J., De Preter, V., Arijs, I., Eeckhaut, V., Ballet, V., Claes, K., Van Immerseel, F., Verbeke, K., et al. (2014) · Gut · doi:10.1136/gutjnl-2013-304833 · Cited by 1,904
Interactions between commensal intestinal bacteria and the immune system
Macpherson, A. J., & Harris, N. L. (2004) · Nature reviews. Immunology · doi:10.1038/nri1373 · Cited by 1,683
The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota
Round, J. L., Lee, S. M., Li, J., Tran, G., Jabri, B., Chatila, T. A., & Mazmanian, S. K. (2011) · Science · doi:10.1126/science.1206095 · Cited by 1,604
The role of gut microbiota in immune homeostasis and autoimmunity
Wu, H.-J., & Wu, E. (2012) · Gut Microbes · doi:10.4161/gmic.19320 · Cited by 1,426
Borsellino, G., Kleinewietfeld, M., Mitri, D. D., Sternjak, A., Diamantini, A., Giometto, R., Höpner, S., Centonze, D., Bernardi, G., Dell’Acqua, M. L., et al. (2007) · Blood · doi:10.1182/blood-2006-12-064527 · Cited by 1,287
CD39 and CD73 in immunity and inflammation
Antonioli, L., Pacher, P., Vizi, E. S., & Haskó, G. (2013) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2013.03.005 · Cited by 1,269
Allan, S. E., Crome, S. Q., Crellin, N. K., Passerini, L., Steiner, T. S., Bacchetta, R., Roncarolo, M. G., & Levings, M. K. (2007) · International Immunology · doi:10.1093/intimm/dxm014 · Cited by 872
Tran, D. Q., Ramsey, H. E., & Shevach, E. M. (2007) · Blood · doi:10.1182/blood-2007-06-094656 · Cited by 738
Ochoa-Repáraz, J., Mielcarz, D. W., Wang, Y., Begum-Haque, S., Dasgupta, S., Kasper, D. L., & Kasper, L. H. (2010) · Mucosal Immunology · doi:10.1038/mi.2010.29 · Cited by 507
Self-citationCD39+Foxp3+ Regulatory T Cells Suppress Pathogenic Th17 Cells and Are Impaired in Multiple Sclerosis
Fletcher, J. M., Lonergan, R. M., Costelloe, L., Kinsella, K., Moran, B., O’Farrelly, C., Tubridy, N. J., & Mills, K. H. G. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901881 · Cited by 476
Intestinal Commensal Microbes as Immune Modulators
Ivanov, I. I., & Honda, K. (2012) · Cell Host & Microbe · doi:10.1016/j.chom.2012.09.009 · Cited by 437
MHC Class II Expression Identifies Functionally Distinct Human Regulatory T Cells
Baecher‐Allan, C., Wolf, E., & Hafler, D. A. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.8.4622 · Cited by 420
Wang, L., Pino‐Lagos, K., de Vries, V. C., Guleria, I., Sayegh, M. H., & Noelle, R. J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0710441105 · Cited by 405
Venken, K., Hellings, N., Thewissen, M. M., Somers, V. A., Hensen, K., Rummens, J., Medaer, R., Hupperts, R., & Stinissen, P. (2007) · Immunology · doi:10.1111/j.1365-2567.2007.02690.x · Cited by 376
Decreased FOXP3 levels in multiple sclerosis patients
Huan, J., Culbertson, N. E., Spencer, L., Bartholomew, R. M., Burrows, G. G., Chou, Y. K., BOURDETTE, D. N., Ziegler, S. F., Offner, H., & Vandenbark, A. A. (2005) · Journal of Neuroscience Research · doi:10.1002/jnr.20522 · Cited by 369
Ochoa-Repáraz, J., Mielcarz, D. W., Ditrio, L. E., Burroughs, A. R., Begum-Haque, S., Dasgupta, S., Kasper, D. L., & Kasper, L. H. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1001443 · Cited by 367 · cited 1×
“This unique polysaccharide possesses the capacity to elicit T cell responses that are essential to the immune regulatory effects observed in hosts.(4,6) The otherwise Th2-skewed immune system in GF mice is rebalanced to reflect appropriate Th1 responses upon B.”
BackgroundSelf-citationTransient regulatory T-cells: A state attained by all activated human T-cells
Pillai, V., Ortega, S. B., Wang, C. K., & Karandikar, N. J. (2006) · Clinical Immunology · doi:10.1016/j.clim.2006.10.014 · Cited by 344
Polysaccharide processing and presentation by the MHCII pathway
Cobb, B. A., Wang, Q., Tzianabos, A. O., & Kasper, D. L. (2004) · Cell · doi:10.1016/j.cell.2004.05.001 · Cited by 340
Self-citationDasgupta, S., Erturk-Hasdemir, D., Ochoa-Reparaz, J., Reinecker, H.-C., & Kasper, D. L. (2014) · Cell Host & Microbe · doi:10.1016/j.chom.2014.03.006 · Cited by 292
Self-citationFriedman, D. J., Künzli, B. M., A-Rahim, Y. I., Sevigny, J., Berberat, P. O., Enjyoji, K., Csizmadia, E., Friess, H., & Robson, S. C. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0902869106 · Cited by 284
Levels of Foxp3 in Regulatory T Cells Reflect Their Functional Status in Transplantation
Chauhan, S. K., Saban, D. R., Lee, H. K., & Dana, R. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.182.1.148 · Cited by 261
Impaired regulatory T cell function in germ‐free mice
Östman, S., Rask, C., Wold, A. E., Hultkrantz, S., & Telemo, E. (2006) · European Journal of Immunology · doi:10.1002/eji.200535244 · Cited by 257
Sawant, D. V., & Vignali, D. A. A. (2014) · Immunological Reviews · doi:10.1111/imr.12173 · Cited by 255
Haas, J., Fritzsching, B., Trübswetter, P., Korporal, M., Milkova, L., Fritz, B., Vobis, D., Krammer, P. H., Suri‐Payer, E., & Wildemann, B. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.2.1322 · Cited by 253
Allan, S. E., McMurchy, A. N., Mérindol, N., Crellin, N. K., Amendola, M., Bacchetta, R., Naldini, L., Roncarolo, M. G., Soudeyns, H., & Levings, M. K. (2007) · Molecular Therapy · doi:10.1038/sj.mt.6300341 · Cited by 233
FOXP3 and scurfy: how it all began
Ramsdell, F., & Ziegler, S. F. (2014) · Nature reviews. Immunology · doi:10.1038/nri3650 · Cited by 225
Hippen, K. L., Merkel, S. C., Schirm, D. K., Nelson, C. E., Tennis, N. C., Riley, J. L., June, C. H., Miller, J. S., Wagner, J. E., & Blazar, B. R. (2011) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2011.03558.x · Cited by 221
Expression of CD39 by Human Peripheral Blood CD4+CD25+ T Cells Denotes a Regulatory Memory Phenotype
Dwyer, K. M., Hanidziar, D., Putheti, P., Hill, P., Pommey, S., McRae, J. L., Winterhalter, A. C., Doherty, G. A., Deaglio, S., Koulmanda, M., et al. (2010) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2010.03291.x · Cited by 217
Pop, S. M., Wong, C. P., Culton, D. A., Clarke, S. H., & Tisch, R. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20042398 · Cited by 210
Wang, Y., Telesford, K. M., Ochoa‐Repáraz, J., Haque-Begum, S., Christy, M., Kasper, E. J., Wang, L., Wu, Y., Robson, S. C., Kasper, D. L., et al. (2014) · Nature Communications · doi:10.1038/ncomms5432 · Cited by 208
Self-citationZwitterionic Polysaccharides Stimulate T Cells by MHC Class II-Dependent Interactions
Kalka-Moll, W. M., Tzianabos, A. O., Bryant, P. W., Niemeyer, M., Ploegh, H. L., & Kasper, D. L. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.11.6149 · Cited by 156
Self-citationGut Microbiome and Multiple Sclerosis
Bhargava, P., & Mowry, E. M. (2014) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-014-0492-2 · Cited by 129
Schuler, P. J., Schilling, B., Harasymczuk, M., Hoffmann, T. K., Johnson, J. T., Lang, S., & Whiteside, T. L. (2012) · European Journal of Immunology · doi:10.1002/eji.201142347 · Cited by 114
Zwitterionic capsular polysaccharides: the new MHCII-dependent antigens
Cobb, B. A., & Kasper, D. L. (2005) · Cellular Microbiology · doi:10.1111/j.1462-5822.2005.00591.x · Cited by 96
Self-citationCD39 and CD161 Modulate Th17 Responses in Crohn's Disease
Bai, A., Moss, A. C., Kokkotou, E. G., Usheva, A., Sun, X., Cheifetz, A. S., Zheng, Y., Longhi, M. S., Gao, W., Wu, Y., et al. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1400346 · Cited by 92
Kisielewicz, A., Schaier, M., Schmitt, E., Hug, F., Haensch, G. M., Meuer, S. C., Zeier, M. G., Sohn, C., & Steinborn, A. (2010) · Clinical Immunology · doi:10.1016/j.clim.2010.07.008 · Cited by 67
Peelen, E., Damoiseaux, J. G. M. C., Smolders, J., Knippenberg, S. A. M., Menheere, P. P. C. A., Tervaert, J. W. C., Hupperts, R., & Thewissen, M. M. (2011) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2011.09.013 · Cited by 61
Herrath, J., Chemin, K., Albrecht, I., Catrina, A. I., & Malmström, V. (2014) · European Journal of Immunology · doi:10.1002/eji.201344140 · Cited by 56
Baecher‐Allan, C., Costantino, C. M., Cvetanovich, G. L., Ashley, C. W., Bériou, G., Dominguez‐Villar, M., & Hafler, D. A. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1002502 · Cited by 53
Fingolimod Increases CD39-Expressing Regulatory T Cells in Multiple Sclerosis Patients
Muls, N., Dang, H. A., Sindic, C. J. M., & Pesch, V. V. (2014) · PLoS ONE · doi:10.1371/journal.pone.0113025 · Cited by 52
王, 钊. (2015) · Hans Journal of Nanotechnology · doi:10.12677/nat.2015.51001 · Cited by 51
Glycoantigens Induce Human Peripheral Tr1 Cell Differentiation with Gut-homing Specialization
Kreisman, L. S. C., & Cobb, B. A. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.206011 · Cited by 38
Stephen, T. L., Niemeyer, M., Tzianabos, A. O., Krönke, M., Kasper, D. L., & Kalka-Moll, W. M. (2005) · Infection and Immunity · doi:10.1128/iai.73.4.2184-2189.2005 · Cited by 36
Self-citationRapamycin Regulates iTreg Function through CD39 and Runx1 Pathways
Lu, Y., Wang, J., Gu, J., Lu, H., Li, X., Qian, X., Liu, X., Wang, X., Zhang, F., & Lu, L. (2014) · Journal of Immunology Research · doi:10.1155/2014/989434 · Cited by 24
Research works printed but not linked: 3
- Ochoa-Repáraz J, 2010, Mucosal immunology, 1
- Lu Y, 2014, J Immunol Res, 1
- Ramsdell F, 2014, Nat Pub Group, 14, 343
Cited by
Sorted by citations
Gut microbiota, metabolites and host immunity
Rooks, M. G., & Garrett, W. S. (2016) · Nature reviews. Immunology · doi:10.1038/nri.2016.42 · Cited by 3,409
Lactobacillus reuteri induces gut intraepithelial CD4 + CD8αα + T cells
Cervantes-Barragan, L., Chai, J. N., Tianero, M. D., Di Luccia, B., Ahern, P. P., Merriman, J., Cortez, V. S., Caparon, M. G., Donia, M. S., Gilfillan, S., et al. (2017) · Science · doi:10.1126/science.aah5825 · Cited by 896
Postler, T. S., & Ghosh, S. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.05.008 · Cited by 876
“…PSA also activates toll-like receptor (TLR) 2 expressed on the surface of DCs, which triggers the release of cytokines that promote IL-10 production by T cells (Cobb et al., 2004; Dasgupta et al., 2014; Johnson et al., 2015; Mazmanian et al., 2005, 2008; Telesford et al., 2015; Wang et al., 2006).”
BackgroundLeaky Gut As a Danger Signal for Autoimmune Diseases
Mu, Q., Kirby, J. L., Reilly, C. M., & Luo, X. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00598 · Cited by 634
The gut microbiota influences anticancer immunosurveillance and general health
Routy, B., Gopalakrishnan, V., Daillère, R., Zitvogel, L., Wargo, J. A., & Kroemer, G. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-018-0006-2 · Cited by 523
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
