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Essential Role of the E3 Ubiquitin Ligase Cbl-b in T Cell Anergy Induction
Open accessAbstract
Antigen-specific immunotolerance limits the expansion of self-reactive T cells involved in autoimmune diseases. Here, we show that the E3 ubiquitin ligase Cbl-b is upregulated in T cells after tolerizing signals. Loss of Cbl-b in mice results in impaired induction of T cell tolerance both in vitro and in vivo. Importantly, rechallenge of Cbl-b mutant mice with the tolerizing antigen results in massive lethality. Moreover, ablation of Cbl-b resulted in exacerbated autoimmunity. Mechanistically, loss of Cbl-b rescues reduced calcium mobilization of anergic T cells, which was attributed to Cbl-b-mediated regulation of PLCgamma-1 phosphorylation. Our results show a critical role for Cbl-b in the regulation of peripheral tolerance and anergy of T cells.
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“The E3 ubiquiting ligase family can affect PI3K, mTOR, and Ras/MAPK signaling pathways and help to actively maintain anergy [21,23,24].”
From T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment (2013) · cites this paper as [23]
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Metadata
- Authors
- Jeon, M.-S., Atfield, A., Venuprasad, K., Krawczyk, C., Sarao, R., Elly, C., Yang, C., Arya, S., Bachmaier, K., Su, L., Bouchard, D., Jones, R., Gronski, M., Ohashi, P., Wada, T., Bloom, D., Fathman, C. G., Liu, Y.-C., & Penninger, J. M.
- Affiliations
- La Jolla Institute for Immunology (US)
- University of Toronto (CA)
- Institute of Molecular Biotechnology (AT)
- Stanford Medicine (US)
- Corresponding author
- Liu, Yun-Cai
- Penninger, Josef M.
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2004-08
- Volume
- 21
- Issue
- 2
- Pages
- 167-177
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2039096179
- Cited by
- 348
- References
- 33
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 10 · 2023: 5 · 2022: 8 · 2021: 16 · 2020: 12 · 2019: 13 · 2018: 10 · 2017: 15 · 2016: 12 · 2015: 19 · 2014: 23 · 2013: 22 · 2012: 20
- FWCI
- 8.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ai050280-05)
- U.S. Public Health Service (R0156558)
- National Institute of Allergy and Infectious Diseases (R01 AI 50280)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- Cbl-b, E3 ubiquitin ligase, T cell anergy, T cell tolerance, antigen-specific tolerance, autoimmunity, calcium mobilization, peripheral tolerance, autoreactive T cells
- MeSH terms
- Animals, Antigens, Enterotoxins, Type C Phospholipases, T-Lymphocytes, Clonal Anergy, Adoptive Transfer, Ubiquitin-Protein Ligases, Adaptor Proteins, Signal Transducing, Proto-Oncogene Proteins c-cbl, Mice, Phospholipase C gamma, In Vitro Techniques
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