Nuclear factor of activated T cells regulates the expression of interleukin-4 in Th2 cells in an all-or-none fashion
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Nuclear factor of activated T cells regulates the expression of interleukin-4 in Th2 cells in an all-or-none fashion. / Köck, Juliana; Kreher, Stephan; Lehmann, Katrin; Riedel, René; Bardua, Markus; Lischke, Timo; Jargosch, Manja; Haftmann, Claudia; Bendfeldt, Hanna; Hatam, Farahnaz; Mashreghi, Mir-Farzin; Baumgrass, Ria; Radbruch, Andreas; Chang, Hyun-Dong.
in: J BIOL CHEM, Jahrgang 289, Nr. 39, 26.09.2014, S. 26752-26761.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Nuclear factor of activated T cells regulates the expression of interleukin-4 in Th2 cells in an all-or-none fashion
AU - Köck, Juliana
AU - Kreher, Stephan
AU - Lehmann, Katrin
AU - Riedel, René
AU - Bardua, Markus
AU - Lischke, Timo
AU - Jargosch, Manja
AU - Haftmann, Claudia
AU - Bendfeldt, Hanna
AU - Hatam, Farahnaz
AU - Mashreghi, Mir-Farzin
AU - Baumgrass, Ria
AU - Radbruch, Andreas
AU - Chang, Hyun-Dong
N1 - © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2014/9/26
Y1 - 2014/9/26
N2 - Th2 memory lymphocytes have imprinted their Il4 genes epigenetically for expression in dependence of T cell receptor restimulation. However, in a given restimulation, not all Th cells with a memory for IL-4 expression express IL-4. Here, we show that in reactivated Th2 cells, the transcription factors NFATc2, NF-kB p65, c-Maf, p300, Brg1, STAT6, and GATA-3 assemble at the Il4 promoter in Th2 cells expressing IL-4 but not in Th2 cells not expressing it. NFATc2 is critical for assembly of this transcription factor complex. Because NFATc2 translocation into the nucleus occurs in an all-or-none fashion, dependent on complete dephosphorylation by calcineurin, NFATc2 controls the frequencies of cells reexpressing Il4, translates analog differences in T cell receptor stimulation into a digital decision for Il4 reexpression, and instructs all reexpressing cells to express the same amount of IL-4. This analog-to-digital conversion may be critical for the immune system to respond to low concentrations of antigens.
AB - Th2 memory lymphocytes have imprinted their Il4 genes epigenetically for expression in dependence of T cell receptor restimulation. However, in a given restimulation, not all Th cells with a memory for IL-4 expression express IL-4. Here, we show that in reactivated Th2 cells, the transcription factors NFATc2, NF-kB p65, c-Maf, p300, Brg1, STAT6, and GATA-3 assemble at the Il4 promoter in Th2 cells expressing IL-4 but not in Th2 cells not expressing it. NFATc2 is critical for assembly of this transcription factor complex. Because NFATc2 translocation into the nucleus occurs in an all-or-none fashion, dependent on complete dephosphorylation by calcineurin, NFATc2 controls the frequencies of cells reexpressing Il4, translates analog differences in T cell receptor stimulation into a digital decision for Il4 reexpression, and instructs all reexpressing cells to express the same amount of IL-4. This analog-to-digital conversion may be critical for the immune system to respond to low concentrations of antigens.
KW - Active Transport, Cell Nucleus/physiology
KW - Adaptor Proteins, Signal Transducing/genetics
KW - Animals
KW - Cell Nucleus/genetics
KW - DNA Helicases/genetics
KW - E1A-Associated p300 Protein/genetics
KW - GATA3 Transcription Factor/genetics
KW - Gene Expression Regulation/physiology
KW - Interleukin-4/biosynthesis
KW - Mice
KW - Mice, Inbred BALB C
KW - Mice, Transgenic
KW - NFATC Transcription Factors/genetics
KW - Nuclear Proteins/genetics
KW - Phosphorylation/physiology
KW - Receptors, Antigen, T-Cell/genetics
KW - Response Elements/physiology
KW - STAT6 Transcription Factor/genetics
KW - Th2 Cells/cytology
KW - Transcription Factor RelA/genetics
KW - Transcription Factors/genetics
U2 - 10.1074/jbc.M114.587865
DO - 10.1074/jbc.M114.587865
M3 - SCORING: Journal article
C2 - 25037220
VL - 289
SP - 26752
EP - 26761
JO - J BIOL CHEM
JF - J BIOL CHEM
SN - 0021-9258
IS - 39
ER -