Cbl-b and itch: key regulators of peripheral T-cell tolerance.
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.
Venuprasad
K
K
Department of Immunology and Microbiology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. poojaryv@karmanos.org
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*
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
J Clin Invest. 2006 Apr;116(4):1117-26
16557301
Nat Immunol. 2002 Mar;3(3):281-7
11828324
Nat Rev Cancer. 2005 Apr;5(4):263-74
15776005
Nat Med. 2004 Nov;10(11):1234-9
15467726
Cell. 2008 May 30;133(5):775-87
18510923
Immunity. 2004 Aug;21(2):167-77
15308098
Adv Exp Med Biol. 2006;584:207-17
16802609
J Clin Invest. 2007 Apr;117(4):1029-36
17364027
Nat Immunol. 2005 May;6(5):472-80
15834410
Nature. 2000 Jan 13;403(6766):211-6
10646608
Cell. 2002 Jun 14;109(6):719-31
12086671
Mol Cell. 2005 Sep 2;19(5):581-93
16137616
Nature. 2000 Jan 13;403(6766):216-20
10646609
Cell. 2003 Jun 13;113(6):685-700
12809600
Nat Immunol. 2004 Mar;5(3):255-65
14973438
Science. 2004 Oct 8;306(5694):271-5
15358865
Nat Rev Immunol. 2002 Jan;2(1):11-9
11908514
J Immunol. 2006 Feb 1;176(3):1316-20
16424156
Nat Immunol. 2008 Mar;9(3):245-53
18278048
J Exp Med. 2007 Apr 16;204(4):879-91
17403934