title: Control of IFN-γ production and regulatory function by the inducible nuclear protein IκB-ζ in T cells.
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.
authors.affiliation: *Laboratory of Cell Recognition and Response, Graduate School of Life Sciences, and Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan; School of Medicine, Gifu University, Gifu, Japan; Department of Microbiology and Immunology, School of Medicine, Keio University, Tokyo, Japan; and Mucosal Immunology Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA ta-maru@umin.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: MaruYama
authors.affiliation: *Laboratory of Cell Recognition and Response, Graduate School of Life Sciences, and Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan; School of Medicine, Gifu University, Gifu, Japan; Department of Microbiology and Immunology, School of Medicine, Keio University, Tokyo, Japan; and Mucosal Immunology Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Kobayashi
authors.affiliation: *Laboratory of Cell Recognition and Response, Graduate School of Life Sciences, and Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan; School of Medicine, Gifu University, Gifu, Japan; Department of Microbiology and Immunology, School of Medicine, Keio University, Tokyo, Japan; and Mucosal Immunology Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Kouetsu
authors.initials: K
authors.lastname: Ogasawara
authors.affiliation: *Laboratory of Cell Recognition and Response, Graduate School of Life Sciences, and Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan; School of Medicine, Gifu University, Gifu, Japan; Department of Microbiology and Immunology, School of Medicine, Keio University, Tokyo, Japan; and Mucosal Immunology Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshimura
authors.affiliation: *Laboratory of Cell Recognition and Response, Graduate School of Life Sciences, and Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan; School of Medicine, Gifu University, Gifu, Japan; Department of Microbiology and Immunology, School of Medicine, Keio University, Tokyo, Japan; and Mucosal Immunology Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: WanJun
authors.initials: W
authors.lastname: Chen
authors.affiliation: *Laboratory of Cell Recognition and Response, Graduate School of Life Sciences, and Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan; School of Medicine, Gifu University, Gifu, Japan; Department of Microbiology and Immunology, School of Medicine, Keio University, Tokyo, Japan; and Mucosal Immunology Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Muta
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000378:metabolism*; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000172:deficiency / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C485947:Nfkbiz protein, mouse; D009687:Nuclear Proteins; D053773:Transforming Growth Factor beta1; D007371:Interferon-gamma
keywords: T lymphocyte; cytokine; transcriptional regulator