A novel function of interferon regulatory factor-1: inhibition of Th2 cells by down-regulating the Il4 gene during Listeria infection.

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-1β 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.

• Authors: Saho Maruyama, Makoto Kanoh, Akira Matsumoto, Makoto Kuwahara, Masakatsu Yamashita, Yoshihiro Asano
• Journal: International immunology (Int Immunol) Vol. 27 Issue 3 Pg. 143-52 (Mar 2015) ISSN: 1460-2377 [Electronic] England
• PMID: 25280793 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Japanese Society for Immunology. 2014. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• 3' Untranslated Regions
• Interferon Regulatory Factor-1
• Interleukin-1
• Receptors, Interleukin-1
• Interleukin-4

Topics

• 3' Untranslated Regions (genetics)
• Animals
• Cell Nucleus (metabolism)
• Cells, Cultured
• Down-Regulation
• Interferon Regulatory Factor-1 (genetics, metabolism)
• Interleukin-1 (metabolism)
• Interleukin-4 (genetics, metabolism)
• Listeria monocytogenes (immunology)
• Listeriosis (immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Protein Transport
• Receptors, Interleukin-1 (metabolism)
• Signal Transduction
• Th1 Cells (immunology, microbiology)
• Th1-Th2 Balance
• Th2 Cells (immunology, microbiology)