scholarly journals Interferon Regulatory Factor 4 (IRF4) Interacts with NFATc2 to Modulate Interleukin 4 Gene Expression

2002 ◽  
Vol 195 (8) ◽  
pp. 1003-1012 ◽  
Author(s):  
Jyothi Rengarajan ◽  
Kerri A. Mowen ◽  
Kathryn D. McBride ◽  
Erica D. Smith ◽  
Harinder Singh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune System ◽  
Lymphocyte Activation ◽  
Interferon Regulatory Factor ◽  
Interleukin 4 ◽  
Physical Interaction ◽  
T Helper ◽  
Regulatory Factor ◽  
Factor C ◽  
Interferon Regulatory Factor 4

Proteins of the nuclear factor of activated T cells (NFAT) family of transcription factors are critical for lymphocyte activation in the immune system. In particular, NFATs are important regulators of inducible IL-4 gene expression. Interferon regulatory factor 4 (IRF4) is an immune system–restricted interferon regulatory factor that is required for lymphocyte activation, but its molecular functions in the T lineage remain to be elucidated. We demonstrate that IRF4 potently synergizes with NFATc2 to specifically enhance NFATc2-driven transcriptional activation of the IL-4 promoter. This function is dependent on the physical interaction of IRF4 with NFATc2. IRF4 synergizes with NFATc2 and the IL-4–inducing transcription factor, c-maf, to augment IL-4 promoter activity as well as to elicit significant levels of endogenous IL-4 production. Furthermore, naïve T helper cells from mice lacking IRF4 are compromised severely for the production of IL-4 and other Th2 cytokines. The identification of IRF4 as a partner for NFATc2 in IL-4 gene regulation provides an important molecular function for IRF4 in T helper cell differentiation.

scholarly journals Dysregulated T helper cell differentiation in the absence of interferon regulatory factor 4

2002 ◽  
Vol 99 (18) ◽  
pp. 11808-11812 ◽  
Author(s):  
M. Lohoff ◽  
H.-W. Mittrucker ◽  
S. Prechtl ◽  
S. Bischof ◽  
F. Sommer ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Interferon Regulatory Factor ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 4

scholarly journals Interferon-Regulatory Factor 4 Is Essential for the Developmental Program of T Helper 9 Cells

Immunity ◽  
2010 ◽  
Vol 33 (2) ◽  
pp. 192-202 ◽  
Author(s):  
Valérie Staudt ◽  
Evita Bothur ◽  
Matthias Klein ◽  
Karen Lingnau ◽  
Sebastian Reuter ◽  
...  
Keyword(s):  
Interferon Regulatory Factor ◽  
T Helper ◽  
Regulatory Factor ◽  
Developmental Program ◽  
Interferon Regulatory Factor 4

scholarly journals Lineage-Specific Modulation of Interleukin 4 Signaling by Interferon Regulatory Factor 4

1999 ◽  
Vol 190 (12) ◽  
pp. 1837-1848 ◽  
Author(s):  
Sanjay Gupta ◽  
Man Jiang ◽  
Alissa Anthony ◽  
Alessandra B. Pernis
Keyword(s):  
Biological Activities ◽  
Cell Types ◽  
Interferon Regulatory Factor ◽  
Lymphoid Cells ◽  
Interleukin 4 ◽  
Regulatory Factor ◽  
Immunoregulatory Cytokine ◽  
Interferon Regulatory Factor 4 ◽  
Inducible Genes ◽  
Different Cell Types

Interleukin (IL)-4 is an immunoregulatory cytokine that exerts distinct biological activities on different cell types. Our studies indicate that interferon regulatory factor (IRF)-4 is both a target and a modulator of the IL-4 signaling cascade. IRF-4 expression is strongly upregulated upon costimulation of B cells with CD40 and IL-4. Furthermore, we find that IRF-4 can interact with signal transducer and activator of transcription (Stat)6 and drive the expression of IL-4–inducible genes. The transactivating ability of IRF-4 is blocked by the repressor factor BCL-6. Since expression of IRF-4 is mostly confined to lymphoid cells, these data provide a potential mechanism by which IL-4–inducible genes can be regulated in a lineage-specific manner.

scholarly journals Regulation of Lymphocyte Apoptosis by Interferon Regulatory Factor 4 (IRF-4)

2003 ◽  
Vol 197 (3) ◽  
pp. 303-314 ◽  
Author(s):  
Jessica C. Fanzo ◽  
Chuan-Min Hu ◽  
So Young Jang ◽  
Alessandra B. Pernis
Keyword(s):  
Lymphoid Cell ◽  
Molecular Mechanisms ◽  
Lymphocyte Activation ◽  
Interferon Regulatory Factor ◽  
Regulatory Factor ◽  
Fas Receptor ◽  
Activation Induced Cell Death ◽  
Human Lymphoid Cell ◽  
Interferon Regulatory Factor 4 ◽  
Deficient Mice

To ensure that homeostasis of the immune system is maintained, the sensitivity of lymphocytes to Fas-mediated apoptosis is differentially regulated during their activation. The molecular mechanisms that link the activation program of lymphocytes to changes in sensitivity to Fas-mediated apoptosis have, however, not been fully characterized. In these studies, we have investigated whether Fas-mediated apoptosis can be regulated by interferon regulatory factor 4 (IRF-4), a lymphoid-restricted member of the IRF family of transcription factors. IRF-4 expression is upregulated during lymphocyte activation and IRF-4–deficient mice have defects in both lymphocyte activation and homeostasis. Here, we show that stable expression of IRF-4 in a human lymphoid cell line that normally lacks IRF-4 leads to a significantly enhanced apoptotic response on Fas receptor engagement. A systematic examination of the downstream effectors of Fas signaling in IRF-4–transfected cells demonstrates an increased activation of caspase-8, as well as an increase in Fas receptor polarization. We demonstrate that IRF-4–deficient mice display defects in activation-induced cell death, as well as superantigen-induced deletion, and that these defects are accompanied by impairments in Fas receptor polarization. These data suggest that IRF-4, by modulating the efficiency of the Fas-mediated death signal, is a novel participant in the regulation of lymphoid cell apoptosis.

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