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

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

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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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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
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
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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