The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
The receptor S1P1 overrides regulatory T cell-mediated immune suppression through Akt-mTOR
Open accessAbstract
Regulatory T cells (T(reg) cells) are critically involved in maintaining immunological tolerance, but this potent suppression must be 'quenched' to allow the generation of adaptive immune responses. Here we report that sphingosine 1-phosphate (S1P) receptor type 1 (S1P1) delivers an intrinsic negative signal to restrain the thymic generation, peripheral maintenance and suppressive activity of T(reg) cells. Combining loss- and gain-of-function genetic approaches, we found that S1P1 blocked the differentiation of thymic T(reg) precursors and function of mature T(reg) cells and affected T(reg) cell-mediated immune tolerance. S1P1 induced selective activation of the Akt-mTOR kinase pathway to impede the development and function of T(reg) cells. Dynamic regulation of S1P1 contributed to lymphocyte priming and immune homeostasis. Thus, by antagonizing T(reg) cell-mediated immune suppression, the lipid-activated S1P1-Akt-mTOR pathway orchestrates adaptive immune responses.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Furthermore, the TTC3 gene is also involved in the regulation of AKT signaling and is related with immune tolerance and neuronal cell survival (Chen et al., 2003; Liu et al., 2009; Pulst, 2016).”
From Identification of Candidate Signature Genes and Key Regulators Associated With Trypanotolerance in the Sheko Breed (2019) · cites this paper as Liu et al., 2009
Experimental — accuracy not yet measured
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
Foxp3 programs the development and function of CD4+CD25+ regulatory T cells
Fontenot, J. D., Gavin, M. A., & Rudensky, A. Y. (2003) · Nature Immunology · doi:10.1038/ni904 · Cited by 7,745
Regulatory T Cells and Immune Tolerance
Sakaguchi, S., Yamaguchi, T., Nomura, T., & Ono, M. (2008) · Cell · doi:10.1016/j.cell.2008.05.009 · Cited by 5,475
Vignali, D. A. A., Collison, L. W., & Workman, C. J. (2008) · Nature Reviews Immunology · doi:10.1038/nri2343 · Cited by 3,463
Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1
Matloubian, M., Lo, C. G., Cinamon, G., Lesneski, M. J., Xu, Y., Brinkmann, V., Allende, M. L., Proia, R. L., & Cyster, J. G. (2004) · Nature · doi:10.1038/nature02284 · Cited by 2,581
Self-citationRegulatory T Cell Lineage Specification by the Forkhead Transcription Factor Foxp3
Fontenot, J. D., Rasmussen, J. P., Williams, L. M., Dooley, J., Farr, A. G., & Rudensky, A. Y. (2005) · Immunity · doi:10.1016/j.immuni.2005.01.016 · Cited by 2,302
Toll Pathway-Dependent Blockade of CD4 + CD25 + T Cell-Mediated Suppression by Dendritic Cells
Pasare, C., & Medzhitov, R. M. (2003) · Science · doi:10.1126/science.1078231 · Cited by 2,000
A function for interleukin 2 in Foxp3-expressing regulatory T cells
Fontenot, J. D., Rasmussen, J. P., Gavin, M. A., & Rudensky, A. Y. (2005) · Nature Immunology · doi:10.1038/ni1263 · Cited by 1,819
CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity
Belkaid, Y., Piccirillo, C. A., Méndez, S., Shevach, E. M., & Sacks, D. L. (2002) · Nature · doi:10.1038/nature01152 · Cited by 1,726
Alteration of Lymphocyte Trafficking by Sphingosine-1-Phosphate Receptor Agonists
MANDALA, S. M., Hajdu, R., Bergstrom, J. D., Quackenbush, E. J., Xie, J., Milligan, J. A., Thornton, R. A., Shei, G.-J., Card, D., Keohane, C.-A., et al. (2002) · Science · doi:10.1126/science.1070238 · Cited by 1,691
The Immune Modulator FTY720 Targets Sphingosine 1-Phosphate Receptors
Brinkmann, V., Davis, M. D., Heise, C. E., Albert, R., Cottens, S., Hof, R., Bruns, C., Prieschl, E. E., Baumruker, T., HIESTAND, P. C., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c200176200 · Cited by 1,512
Flagged first, then by citations
Cited by
Sorted by citations
Items 301–339 of 339
Rodríguez, C. F., Azpiazu, M. D., & Castro, A. (2003) · Revista de la Sociedad Geológica de España · Cited by 1
Mapping the genes for complex canine autoimmune diseases
Massey, J. (2012) · Research Explorer (The University of Manchester) · Cited by 1
Migration of Functionally Specialized T-Helper Cells: TFH Cells, Th17 Cells and FoxP3+ T Cells
Kim, C. H. (2010) · Translational research in biomedicine · doi:10.1159/000274477
Biology Revealed by Sphingosine 1‐Phosphate (S1P) Receptor Gene‐Altered Mice
Allende, M. L., Kono, M., Alexaki, A., Giannouli, C. C., Kang, J., Theisen, C. C., Koerner, E. L., & Proia, R. L. (2013) · Wiley eBooks · doi:10.1002/9781118531426.ch23
Self-citationS1P receptor agonists, a novel generation of immunosuppressants
Almagro, R. L., Tarrasón, G., & Godessart, N. (2010) · Cambridge University Press eBooks · doi:10.1017/cbo9780511760334.018
Signals Controlling Regulatory T Cell Differentiation and Homeostasis
Zou, T. (2012) · ScholarlyCommons (University of Pennsylvania)
Kim, Y. U. (2015) · Digital Commons-TMC (Texas Medical Center)
Transcriptomic changes of the gut in dairy calves during pre-weaned period
Liang, G. (2016) · ERA: Education and Research Archive (University of Alberta) · doi:10.7939/r39882v9t
Wang, H., Fang, K., & Chang, X. (2020) · doi:10.21203/rs.2.20626/v1
Caspi, R. R., & Chaon, B. (2012) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.13477043.15750073
McCune, J. M., & Bronevetsky, Y. (2013) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.718027780.793482746
Mapara, M. Y., & Lu, C. (2010) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.5667958.5640057
Lysophospholipid (S1P) receptors in GtoPdb v.2023.1
Blaho, V. A., Chun, J. J. M., Herr, D. R., Jones, D. G., Jonnalagadda, D., & Kihara, Y. (2023) · IUPHAR/BPS Guide to Pharmacology CITE · doi:10.2218/gtopdb/f135/2023.1
Expression of inflammatory mediators in CD103+ and CD103- T cells isolated from periodontitis tissue
Isaraphithakkul, B., Mahanonda, R., & Pichyangkul, S. (2017) · doi:10.58837/chula.the.2017.396
Coulombeau, R., Selck, C., Giang, N., Al-Mohammad, A., Ng, N., Maher, A. K., Argüello, R. J., Scalfari, A., Varley, J. A., Nicholas, R. S., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.05.20.594966
Immunometabolism Governs T Cell Immunity
Raynor, J. L., Shi, H., & Chi, H. (2025) · Elsevier eBooks · doi:10.1016/b978-0-12-824465-4.00275-1
Self-citationLoschinski, R., Karl, F., Drettwan, D., Wittmann, J., Jacobs, B., Völkl, S., Bruns, H., Mackensen, A., & Mougiakakos, D. (2025) · Clinical & Translational Immunology · doi:10.1002/cti2.70060
Combination Strategies for Stem Cell Mobilization Targeting CXCR4 and S1P Receptors
Harun, N., Bradstock, K. F., & Bendall, L. J. (2011) · Springer eBooks · doi:10.1007/978-1-4614-1960-0_3
Malone, K., Díaz, A. D., Shearer, J. A., Moore, A., & Waeber, C. (2021) · Figshare · doi:10.6084/m9.figshare.13669408
Malone, K., Díaz, A. D., Shearer, J. A., Moore, A., & Waeber, C. (2021) · Figshare · doi:10.6084/m9.figshare.13669402
Malone, K., Díaz, A. D., Shearer, J. A., Moore, A., & Waeber, C. (2021) · Figshare · doi:10.6084/m9.figshare.13669405
Malone, K., Díaz, A. D., Shearer, J. A., Moore, A., & Waeber, C. (2021) · Figshare · doi:10.6084/m9.figshare.13669414
Malone, K., Díaz, A. D., Shearer, J. A., Moore, A., & Waeber, C. (2021) · Figshare · doi:10.6084/m9.figshare.13669411
Lin, Y., Seno, T., Hsu, A. Y.-H., Cartier, A., Kuo, A., Levesque, M. V., Ghosh, A., Fohmann, I., Blaho, V. A., Galvani, S., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.05.703783
Impact des inhibiteurs de la voie mTOR sur la réponse immunitaire T anti-tumorale
Beziaud, L. (2015) · theses.fr (ABES) · doi:10.70675/02936eacz6998z4fd1zb56cz2535d854411e
Hamdani, S. (2016) · theses.fr (ABES) · doi:10.70675/9e24450czb094z4495zafbfz117b8e3adf32
Implication de la GTPase RagA dans l’activation et la polarisation de la réponse lymphocytaire T
Attia, M. (2017) · theses.fr (ABES) · doi:10.70675/54b64a32zdbe2z447dzaab4z42858c3a25e6
Lin, Y., Seno, T., Hsu, A. Y.-H., Cartier, A., Kuo, A., Levesque, M. V., Ghosh, A., Fohmann, I., Blaho, V. A., Galvani, S., et al. (2026) · eLife · doi:10.7554/elife.112544
Lin, Y., Seno, T., Hsu, A. Y.-H., Cartier, A., Kuo, A., Levesque, M. V., Ghosh, A., Fohmann, I., Blaho, V. A., Galvani, S., et al. (2026) · eLife · doi:10.7554/elife.112544.1
Ling, Z.-G., Xiang, T.-W., Yang, C., Zhang, D.-Y., You, Y.-H., Xiao, S.-Y., Xie, L.-L., Tan, J.-L., Dai, Q.-J., Huang, G., et al. (2026) · Gut microbes · doi:10.1080/19490976.2026.2739669
Self-citation
Metadata
- Authors
- Liu, G., Burns, S., Huang, G., Boyd, K., Proia, R. L., Flavell, R. A., & Chi, H.
- Affiliations
- St. Jude Children's Research Hospital (US)
- National Institutes of Health (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Chi, Hongbo
- Venue
- Nature Immunology
- Published
- 2009-05-31
- Volume
- 10
- Issue
- 7
- Pages
- 769-777
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC2732340
- OpenAlex
- W1989291933
- Cited by
- 339
- References
- 50
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 15 · 2023: 13 · 2022: 15 · 2021: 21 · 2020: 15 · 2019: 18 · 2018: 11 · 2017: 25 · 2016: 23 · 2015: 26 · 2014: 28 · 2013: 22 · 2012: 34
- FWCI
- 13.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS064599)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (K01AR053573)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- S1P1 receptor, sphingosine-1-phosphate, regulatory T cells, Akt/mTOR signaling, immune tolerance, immunosuppression, peripheral tolerance, lymphocyte priming, immune homeostasis, lipid signaling
- MeSH terms
- Animals, Animals, Newborn, Carrier Proteins, Cell Differentiation, Colon, Female, Flow Cytometry, Homeostasis, Immune Tolerance, Male, Mice, Inbred C57BL, Mice, Transgenic, Thymus Gland, Signal Transduction, CD4-Positive T-Lymphocytes, Leukocyte Common Antigens, Phosphotransferases (Alcohol Group Acceptor), Mice, Knockout, Adoptive Transfer, Receptors, Lysosphingolipid, T-Lymphocytes, Regulatory, Proto-Oncogene Proteins c-akt, Mice, Forkhead Transcription Factors, Interleukin-2 Receptor alpha Subunit, TOR Serine-Threonine Kinases
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
