A novel function of interferon regulatory factor-1: inhibition of T(h)2 cells by down-regulating the Il4 gene during Listeria infection

作者：Maruyama Saho^*; Kanoh Makoto; Matsumoto Akira; Kuwahara Makoto; Yamashita Masakatsu; Asano Yoshihiro

来源：International Immunology, 2015, 27(3): 143-152.

DOI：10.1093/intimm/dxu092

• IL-1
• interferon regulatory factor-1
• Listeria monocytogenes
• silencer
• T-h subset

Infection with certain pathogens induces a shift of the T-h subset balance to a T(h)1 dominant state. This, in turn, results in the suppression of T(h)2 responses. We focused on the involvement of interferon regulatory factor-1 (IRF-1) in the suppression of T(h)2 cells during Listeria infection. We found that the inhibition of IL-4 production by T(h)2 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 T(h)2 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-1 alpha and IL-1 beta 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 T(h)2 cells. As a result, the immune system shifts predominantly to a T(h)1 response during Listeria infection, resulting in effective protection of the host.

• 出版日期2015-3