Cited by 339T-cell and B-cell ImmunologySphingolipid Metabolism and SignalingPsoriasis: Treatment and Pathogenesis

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The receptor S1P1 overrides regulatory T cell-mediated immune suppression through Akt-mTOR

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Liu, Guangwei, Burns, Samir, Huang, Gonghua, Boyd, Kelli, Proia, Richard L, Flavell, Richard A, Chi, Hongbo·2009·Nature Immunology

DOI 10.1038/ni.1743PMC PMC2732340

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Abstract

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.

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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
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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
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Self-citation
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Zeng, H., & Chi, H. (2014) · Transcription · doi:10.4161/trns.28263 · Cited by 45
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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
ORCID: Liu, Guangwei
Huang, Gonghua
Boyd, Kelli
Proia, Richard L
Flavell, Richard A
Chi, Hongbo
Venue: Nature Immunology
Publisher: Springer Science and Business Media LLC
Published: 2009-05-31
Volume: 10
Issue: 7
Pages: 769-777
ISSN: 1529-2908 (ISSN-L)
1529-2916
DOI: 10.1038/ni.1743
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

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The receptor S1P1 overrides regulatory T cell-mediated immune suppression through Akt-mTOR

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