Control of IFN-γ production and regulatory function by the inducible nuclear protein IκB-ζ in T cells.

The transcriptional regulator IκB-ζ is important for the control of apoptosis in keratinocytes. Thus， IκB-ζ-deficient mice develop autoimmune diseases， such as Sjögren's syndrome. However， T cells also play a pivotal role in Sjögren's syndrome. To study the role of IκB-ζ in T cells， we generated T cell-specific， IκB-ζ-deficient mice. We observed increased numbers of peripheral effector/memory CD4(+) cells and IFN-γ-producing CD4(+) cells in 3-week-old mice. We found that IκB-ζ can be up-regulated by TGF-β1 in naïve CD4(+) T cells and that it negatively regulates IFN-γ expression. In addition， we generated Treg-specific， IκB-ζ deficient mice and found that IκB-ζ is dispensable for the plasticity and stability of Tregs. However， Tregs from T cell-specific， IκB-ζ-deficient mice have reduced immunoregulatory function. Thus， our data reveal a previously unappreciated role for IκB-ζ in IFN-γ production in T cells and the immunoregulatory function of Tregs.