A novel function of interferon regulatory factor-1: inhibition of Th2 cells by down-regulating the Il4 gene during Listeria infection
A novel function of interferon regulatory factor-1: inhibition of Th2 cells by down-regulating the Il4 gene during Listeria infection
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DOI：
10.1093/intimm/dxu092
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发表时间：
2015-03-01
影响因子：
4.4
通讯作者：
Asano，Yoshihiro
中科院分区：
文献类型：
--
作者：
Maruyama，Saho;Kanoh，Makoto;Asano，Yoshihiro
Infection with certain pathogens induces a shift of the Thsubset 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 duringListeriainfection. We found that the inhibition of IL-4 production by Th2 cells is mediated by a soluble factor (LmSN) produced byListeria-infected antigen-presenting cells. The inhibition is not observed with T cells fromIrf1gene-targeted mice. IRF-1 suppresses transcription of theIl4gene in Th2 cells. Under the influence of the LmSN, IRF-1 binds to the 3ʹ untranslated region (UTR) region of theIl4gene and down-regulatesIl4gene 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 shiftviaa novel mechanism. Under the influence of IL-1, IRF-1 translocates into the nucleus and acts on the 3ʹUTR region of theIl4gene, thus inhibiting its transcription in Th2 cells. As a result, the immune system shifts predominantly to a Th1 response duringListeriainfection, resulting in effective protection of the host.
