Cited by 349T-cell and B-cell ImmunologyImmune Response and InflammationImmunotherapy and Immune Responses

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Essential Role of the E3 Ubiquitin Ligase Cbl-b in T Cell Anergy Induction

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Jeon, Myung-Shin, Atfield, Alex, Venuprasad, K., Krawczyk, Connie, Sarao, Renu, Elly, Chris, Yang, Chun, Arya, Sudha, Bachmaier, Kurt, Su, Leon, Bouchard, Dennis, Jones, Russel, Gronski, Mathew, Ohashi, Pamela, Wada, Teiji, Bloom, Debra, Fathman, C.Garrison, Liu, Yun-Cai, Penninger, Josef M.·2004·Immunity

DOI 10.1016/j.immuni.2004.07.013

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Abstract

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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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: Jeon, Myung-Shin
Venuprasad, K.
Krawczyk, Connie
Yang, Chun
Bachmaier, Kurt
Su, Leon
Ohashi, Pamela
Wada, Teiji
Fathman, C.Garrison
Liu, Yun-Cai
Penninger, Josef M.
Venue: Immunity
Publisher: Elsevier BV
Published: 2004-08
Volume: 21
Issue: 2
Pages: 167-177
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/j.immuni.2004.07.013
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 3272 d)
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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Essential Role of the E3 Ubiquitin Ligase Cbl-b in T Cell Anergy Induction

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