RRC ID 54355
Author MaruYama T, Kobayashi S, Ogasawara K, Yoshimura A, Chen W, Muta T.
Title Control of IFN-γ production and regulatory function by the inducible nuclear protein IκB-ζ in T cells.
Journal J Leukoc Biol
Abstract 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.
Volume 98(3)
Pages 385-93
Published 2015-9-1
DOI 10.1189/jlb.2A0814-384R
PII jlb.2A0814-384R
PMID 26019294
PMC PMC4541499
MeSH Adaptor Proteins, Signal Transducing / deficiency Adaptor Proteins, Signal Transducing / metabolism* Animals Colitis / chemically induced Colitis / immunology Colitis / pathology Forkhead Transcription Factors / genetics Forkhead Transcription Factors / metabolism Gene Expression Regulation / drug effects HEK293 Cells Homeostasis / drug effects Humans Immune Tolerance / drug effects Interferon-gamma / biosynthesis* Interferon-gamma / genetics Mice, Inbred C57BL Mice, Knockout Nuclear Proteins / deficiency Nuclear Proteins / metabolism* T-Lymphocytes, Regulatory / drug effects T-Lymphocytes, Regulatory / immunology T-Lymphocytes, Regulatory / metabolism* Transforming Growth Factor beta1 / pharmacology
IF 4.224
Times Cited 6
DNA material pGL4.12-mouse IFN-g promoter(600bp) (RDB16732) pcDNA3-FLAG-mouse IkappaB-zeta(L) (RDB16730) pcDNA3-FLAG-mouse IkappaB-zeta(S) (RDB16731) pMY-FLAG-mouse IkB-zeta(L)-IRES-GFP (RDB16733) pMY-FLAG-mouse IkB-zeta(S)-IRES-GFP (RDB16734)