Modulation of T cell cytokine production by interferon regulatory factor-4.
J Biol Chem
; 277(51): 49238-46, 2002 Dec 20.
Article
en En
| MEDLINE
| ID: mdl-12374808
ABSTRACT
Production of cytokines is one of the major mechanisms employed by CD4(+) T cells to coordinate immune responses. Although the molecular mechanisms controlling T cell cytokine production have been extensively studied, the factors that endow T cells with their ability to produce unique sets of cytokines have not been fully characterized. Interferon regulatory factor (IRF)-4 is a lymphoid-restricted member of the interferon regulatory factor family of transcriptional regulators, whose deficiency leads to a profound impairment in the ability of mature CD4(+) T cells to produce cytokines. In these studies, we have investigated the mechanisms employed by IRF-4 to control cytokine synthesis. We demonstrate that stable expression of IRF-4 in Jurkat T cells not only leads to a strong enhancement in the synthesis of interleukin (IL)-2, but also enables these cells to start producing considerable amounts of IL-4, IL-10, and IL-13. Transient transfection assays indicate that IRF-4 can transactivate luciferase reporter constructs driven by either the human IL-2 or the human IL-4 promoter. A detailed analysis of the effects of IRF-4 on the IL-4 promoter reveals that IRF-4 binds to a site adjacent to a functionally important NFAT binding element and that IRF-4 cooperates with NFATc1. These studies thus support the notion that IRF-4 represents one of the lymphoid-specific components that control the ability of T lymphocytes to produce a distinctive array of cytokines.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Proteínas Nucleares
/
Linfocitos T
/
Citocinas
/
Proteínas de Unión al ADN
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2002
Tipo del documento:
Article
País de afiliación:
Estados Unidos