Cbl-b and itch: key regulators of peripheral T-cell tolerance

Cancer Res. 2010 Apr 15;70(8):3009-12. doi: 10.1158/0008-5472.CAN-09-4076.

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.

Keywords: Foxp3; Tolerance; Tregs; Ubiquitination; tumor Immunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Forkhead Transcription Factors / biosynthesis
  • Humans
  • Immune System
  • Immune Tolerance*
  • Mice
  • Neoplasms / metabolism
  • Proto-Oncogene Proteins c-cbl / metabolism*
  • Repressor Proteins / metabolism*
  • Signal Transduction
  • T-Lymphocytes / cytology
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes, Regulatory / cytology
  • Transforming Growth Factor beta1 / metabolism
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Repressor Proteins
  • Transforming Growth Factor beta1
  • ITCH protein, human
  • Itch protein, mouse
  • Proto-Oncogene Proteins c-cbl
  • Ubiquitin-Protein Ligases
  • CBL protein, human
  • Cbl protein, mouse