Expanding roles for GILT in immunity

Gamma-interferon-inducible lysosomal thiol reductase (GILT), a thioredoxin-related oxidoreductase, functions in MHC class II-restricted antigen processing and MHC class I-restricted cross-presentation by reducing disulfide bonds of endocytosed proteins and facilitating their unfolding and optimal degradation. However, recent reports have greatly expanded our understanding of GILT's function. Several studies of GILT and antigen processing have shown that the influence of GILT on the peptide repertoire can alter the character of the immune response and affect central tolerance. Furthermore, a few unexpected roles for GILT have been uncovered: as a host factor for Listeria monocytogenes infection, in the maintenance of cellular glutathione (GSH) levels, and possibly outside the cell, as enzymatically active GILT is secreted by activated macrophages.

Graphical abstractFigure optionsDownload full-size imageDownload high-quality image (166 K)Download as PowerPoint slideHighlights► GILT is exceptionally positioned to regulate a number of cellular functions. ► GILT influences the peptide repertoire and the character of T cell responses. ► GILT has unexpected functions independent of antigen processing.