title: Cbl-b and itch: key regulators of peripheral T-cell tolerance.
abstract: E3 ligases Cbl-b and Itch have emerged as dominant "tolerogenic" regulators of T cells because their deficiency results in severe autoimmune diseases. Cbl-b and Itch ligase activity regulate T-cell anergy and development of Foxp3+ regulatory T cells (Treg) in the periphery by modulating key components of T-cell receptor (TCR) and transforming growth factor-beta (TGF-beta) signaling. Manipulation of Cbl-b and Itch activities may provide unique opportunities to develop future therapies for immune disorders such as autoimmunity and cancer.
authors.affiliation: Department of Immunology and Microbiology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. poojaryv@karmanos.org
authors.forename: K
authors.initials: K
authors.lastname: Venuprasad
mesh_terms: D000818:Animals; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D006801:Humans; D007107:Immune System; D007108:Immune Tolerance; D051379:Mice; D009369:Neoplasms / Q000378:metabolism; D050721:Proto-Oncogene Proteins c-cbl / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012097:Repressor Proteins; D053773:Transforming Growth Factor beta1; C432966:ITCH protein, human; C471637:Itch protein, mouse; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; C067419:CBL protein, human; C493849:Cbl protein, mouse
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