title: 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.affiliation: Department of Immunology, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan saho@m.ehime-u.ac.jp.
authors.forename: Saho
authors.initials: S
authors.lastname: Maruyama
authors.affiliation: Department of Infection and Host Defenses, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kanoh
authors.affiliation: Department of Infection and Host Defenses, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Matsumoto
authors.affiliation: Department of Immunology, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan Translational Research Center, Ehime University Hospital, Toon, Ehime 791-0295, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kuwahara
authors.affiliation: Department of Immunology, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan Department of Infection and Host Defenses, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan.
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Yamashita
authors.affiliation: Department of Immunology, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan Department of Infection and Host Defenses, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Asano
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D015536:Down-Regulation; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D021381:Protein Transport; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology* / Q000382:microbiology; D058408:Th1-Th2 Balance; D018418:Th2 Cells / Q000276:immunology* / Q000382:microbiology
chemical_list: D020413:3' Untranslated Regions; D050856:Interferon Regulatory Factor-1; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D015847:Interleukin-4
keywords: IL-1; Listeria monocytogenes; Th subset; interferon regulatory factor -1; silencer