Diverse cellular and organismal functions of the lysosomal thiol reductase GILT

Matthew P Rausch; Karen Taraszka Hastings

doi:10.1016/j.molimm.2015.06.008

Diverse cellular and organismal functions of the lysosomal thiol reductase GILT

Mol Immunol. 2015 Dec;68(2 Pt A):124-8. doi: 10.1016/j.molimm.2015.06.008. Epub 2015 Jun 23.

Authors

Matthew P Rausch¹, Karen Taraszka Hastings²

Affiliations

¹ Department of Basic Medical Sciences, College of Medicine Phoenix, University of Arizona, Phoenix, AZ, USA; University of Arizona Cancer Center, AZ, USA.
² Department of Basic Medical Sciences, College of Medicine Phoenix, University of Arizona, Phoenix, AZ, USA; University of Arizona Cancer Center, AZ, USA; Department of Immunobiology, College of Medicine, University of Arizona, Tucson, AZ, USA. Electronic address: khasting@email.arizona.edu.

Abstract

Gamma-interferon-inducible lysosomal thiol reductase (GILT) is the only enzyme known to catalyze disulfide bond reduction in the endocytic pathway. GILT facilitates the presentation of a subset of epitopes from disulfide bond-containing antigens. Enhanced presentation of MHC class II-restricted epitopes alters central tolerance and modulates CD4+ T cell-mediated autoimmunity. Improved cross-presentation of viral epitopes results in improved cross-priming of viral-specific CD8+ T cells. GILT regulates the cellular redox state. In GILT-/- cells, there is a shift from the reduced to the oxidized form of glutathione, resulting in mitochondrial autophagy, decreased superoxide dismutase 2, and elevated superoxide levels. GILT expression diminishes cellular activation, including decreased phosphorylated ERK1/2, and decreases cellular proliferation. GILT enhances the activity of bacterial hemolysins, such as listeriolysin O, and increases bacterial replication and infection. GILT expression in cancer cells is associated with improved patient survival. These diverse roles of GILT are discussed.

Keywords: Antigen presentation; Autoimmunity; Cancer; GILT; IFI30; Redox.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Antigen Presentation*
Antigen-Presenting Cells / cytology
Antigen-Presenting Cells / enzymology
Antigen-Presenting Cells / immunology*
Antigens, Viral / genetics
Antigens, Viral / immunology
Autophagy
CD4-Positive T-Lymphocytes / cytology
CD4-Positive T-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / cytology
CD8-Positive T-Lymphocytes / immunology
Cross-Priming
Disulfides / chemistry
Disulfides / immunology
Extracellular Signal-Regulated MAP Kinases / genetics
Extracellular Signal-Regulated MAP Kinases / immunology
Glutathione / immunology
Glutathione / metabolism
Histocompatibility Antigens Class II / genetics
Histocompatibility Antigens Class II / immunology*
Humans
Lysosomes / enzymology
Lysosomes / immunology*
Mitochondria / immunology
Mitochondria / metabolism
Oxidation-Reduction
Oxidoreductases Acting on Sulfur Group Donors / genetics
Oxidoreductases Acting on Sulfur Group Donors / immunology*
Superoxide Dismutase / genetics
Superoxide Dismutase / immunology

Substances

Antigens, Viral
Disulfides
Histocompatibility Antigens Class II
Superoxide Dismutase
superoxide dismutase 2
IFI30 protein, human
Oxidoreductases Acting on Sulfur Group Donors
Extracellular Signal-Regulated MAP Kinases
Glutathione

Grants and funding

R03 AR063259/AR/NIAMS NIH HHS/United States