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

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 +11 more·2004·Immunity

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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Crossref · 10.1016/j.immuni.2004.07.013

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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.
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
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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