A novel function of interferon regulatory factor-1: inhibition of Th2 cells by down-regulating the Il4 gene during Listeria infection.
Int Immunol
; 27(3): 143-52, 2015 Mar.
Article
en En
| MEDLINE
| ID: mdl-25280793
ABSTRACT
Infection with certain pathogens induces a shift of the Th subset balance to a Th1 dominant state. This, in turn, results in the suppression of Th2 responses. We focused on the involvement of interferon regulatory factor-1 (IRF-1) in the suppression of Th2 cells during Listeria infection. We found that the inhibition of IL-4 production by Th2 cells is mediated by a soluble factor (LmSN) produced by Listeria-infected antigen-presenting cells. The inhibition is not observed with T cells from Irf1 gene-targeted mice. IRF-1 suppresses transcription of the Il4 gene in Th2 cells. Under the influence of the LmSN, IRF-1 binds to the 3' untranslated region (UTR) region of the Il4 gene and down-regulates Il4 gene transcription. Finally, we identified IL-1α and IL-1ß as the mediator of the LmSN activity. Signaling through IL-1R induces the stabilization and/or nuclear translocation of IRF-1. We propose that IRF-1 functions to induce the T-cell subset shift via a novel mechanism. Under the influence of IL-1, IRF-1 translocates into the nucleus and acts on the 3'UTR region of the Il4 gene, thus inhibiting its transcription in Th2 cells. As a result, the immune system shifts predominantly to a Th1 response during Listeria infection, resulting in effective protection of the host.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Núcleo Celular
/
Interleucina-4
/
Células Th2
/
Células TH1
/
Factor 1 Regulador del Interferón
/
Listeriosis
/
Listeria monocytogenes
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Int Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Japón