Regulation of immune responses by E3 ubiquitin ligase Cbl-b

Cell Immunol. 2019 Jun:340:103878. doi: 10.1016/j.cellimm.2018.11.002. Epub 2018 Nov 7.

Abstract

Casitas B lymphoma-b (Cbl-b), a RING finger E3 ubiquitin ligase, has been identified as a critical regulator of adaptive immune responses. Cbl-b is essential for establishing the threshold for T cell activation and regulating peripheral T cell tolerance through various mechanisms. Intriguingly, recent studies indicate that Cbl-b also modulates innate immune responses, and plays a key role in host defense to pathogens and anti-tumor immunity. These studies suggest that targeting Cbl-b may represent a potential therapeutic strategy for the management of human immune-related disorders such as autoimmune diseases, infections, tumors, and allergic airway inflammation. In this review, we summarize the latest developments regarding the roles of Cbl-b in innate and adaptive immunity, and immune-mediated diseases.

Keywords: Cbl-b; Immune-related disorders; Innate and adaptive immune responses; T cell tolerance; Ubiquitination.

Publication types

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

MeSH terms

  • Adaptive Immunity / drug effects
  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / immunology
  • Animals
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / pathology
  • Bacterial Infections / drug therapy
  • Bacterial Infections / genetics
  • Bacterial Infections / immunology*
  • Bacterial Infections / pathology
  • Cytokines / genetics
  • Cytokines / immunology
  • Gene Expression Regulation
  • Humans
  • Hypersensitivity / drug therapy
  • Hypersensitivity / genetics
  • Hypersensitivity / immunology*
  • Hypersensitivity / pathology
  • Immunity, Innate / drug effects
  • Immunologic Factors / therapeutic use
  • Lymphocyte Activation
  • Molecular Targeted Therapy / methods
  • Mycoses / drug therapy
  • Mycoses / genetics
  • Mycoses / immunology*
  • Mycoses / pathology
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Peripheral Tolerance / drug effects
  • Proto-Oncogene Proteins c-cbl / genetics*
  • Proto-Oncogene Proteins c-cbl / immunology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology
  • Virus Diseases / drug therapy
  • Virus Diseases / genetics
  • Virus Diseases / immunology*
  • Virus Diseases / pathology

Substances

  • Adaptor Proteins, Signal Transducing
  • Cytokines
  • Immunologic Factors
  • CBLB protein, human
  • Proto-Oncogene Proteins c-cbl