Ask about this productRelated genes to: IRF3 antibody
- Gene:
- IRF3 NIH gene
- Name:
- interferon regulatory factor 3
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 19q13.33
- Locus Type:
- gene with protein product
- Date approved:
- 1996-11-13
- Date modifiied:
- 2017-07-07
Related products to: IRF3 antibody
Related articles to: IRF3 antibody
- Small cell lung cancer (SCLC) is an aggressive malignancy that responds poorly to immune checkpoint inhibitor (ICI) therapy, due to its immunosuppressive tumor microenvironment. Here, we analyse preclinical mouse tumor models and patient-derived SCLC samples and identify Exportin 1 (XPO1) as a regulator of immune suppression in SCLC. Mechanistically, XPO1 drives the nuclear export of TRIM21, enabling TRIM21-dependent proteasomal degradation of IRF3 and repressing the immunostimulatory cytokine TNFSF15. Loss of TNFSF15 promotes TREM2 macrophage polarization, which subsequently attenuates macrophage-dependent IFN-γ-STAT1 signaling and MHC class I expression in tumor cells. Pharmacological or genetic XPO1 blockade restores TNFSF15, constrains TREM2 macrophage differentiation, reactivates antigen presentation, and enhances anti-PD-1 efficacy in preclinical mouse models. Thus, our findings link XPO1-dependent nuclear export to TREM2+ macrophage polarization and support evaluation of XPO1 inhibition in combination with ICIs in SCLC. - Source: PubMed
Publication date: 2026/08/22
Du QingwuQin TingtingWang JingyaJiang YantaoXu QiLi XueyangLiu HuiyanYu JunjieLu YiTong LuyaoSun TaoChen PengJiang RichengHuang Dingzhi - Perfluorooctane sulfonate (PFOS), a prominent per- and polyfluoroalkyl substance (PFAS), has raised significant public health concerns due to its widespread use, environmental persistence, and bioaccumulation potential. Both epidemiological and experimental studies demonstrate that PFOS exposure causes immunotoxicity and disrupts both innate and adaptive immunity. However, the specific effects of PFOS on innate antiviral immunity remain poorly understood. Here, by integrating multi-omics analysis with in vitro and in vivo studies, we establish that PFOS exposure at subtoxic doses compromises antiviral defense by suppressing type I interferon production, thereby enhancing the replication of a broad range of viruses. Mechanistically, PFOS interacts with IRF3 at Val319, Asp328, and Arg341, inducing conformational changes that disrupt the TBK1-IRF3 interaction. This disruption inhibits subsequent IRF3 phosphorylation, dimerization, and nuclear translocation, which in turn suppresses type I interferon production and facilitates viral replication. Additionally, wild-type IRF3, but not a binding-deficient mutant, restores PFOS-mediated suppression of innate antiviral immunity in IRF3-deficient cells or knockout mice. Furthermore, association studies in patients with respiratory syncytial virus, influenza, or hepatitis B virus infection showed that elevated serum PFOS levels are correlated with increased viral loads, as indicated by lower Ct values or higher HBV DNA levels. Similarly, NHANES data link higher serum PFOS to lower vaccine antibody levels. Together, our results demonstrate that PFOS directly targets IRF3 to impair innate antiviral immunity, thereby enhancing host susceptibility to viral infection at environmental exposure levels. - Source: PubMed
Publication date: 2026/09/21
Liang QiujuLi YunSun ZeqingWang LonggeLi ChangyingFang PeiyuZhang QiLi JuanSun XiaoyiChen ChangguoWang ChuGuo GuijieGao MingLiu Sijin - Type I interferon (IFN-I) signaling is crucial for antiviral innate immunity. F-box protein-mediated ubiquitination regulates this pathway. FBXO11 positively regulates IFN-I signaling via TRAF3 K63-linked ubiquitination, but whether other F-box proteins act synergistically during HBV infection remains unknown. This study investigates FBXO32 expression and function in HBV infection, and whether FBXO11 and FBXO32 synergistically activate innate immunity through a NEDD8-dependent mechanism. - Source: PubMed
Publication date: 2026/09/03
Li LiqiangTao ShunZhang YunfeiZeng ZihanLi LiangZhang Jun - Klebsiella pneumoniae (K. pneumoniae) liver abscess (KPLA) is frequently accompanied by thrombophlebitis and systemic inflammation. Argatroban, a direct thrombin inhibitor, has anti-inflammatory potential, but its efficacy and mechanism in KPLA remain unclear. - Source: PubMed
Publication date: 2026/09/17
Wang HongguangChen LuluWang HairuiChang Zhihui - Cytosolic DNA sensing through the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) axis is an important component of innate host defense, whereas sustained pathway activation has been implicated in inflammatory and autoimmune diseases. Although several potent STING inhibitors are in preclinical development and ASP5502 has entered clinical evaluation, no STING inhibitor has received regulatory approval. Screening of an FDA-approved compound library identified vitamin K3 (VK3; menadione), a synthetic vitamin K analogue, as a compound that attenuated cellular responses elicited by SR717 and 2'3'-cGAMP. VK3 reduced IRF3 phosphorylation and the expression of interferon-related and inflammatory genes. In a cellular thermal shift assay (CETSA), VK3 did not produce detectable thermal stabilization of STING; therefore, its direct molecular target remains undefined. VK3 did not significantly reduce short-term THP-1 cell viability at the concentration used for signaling experiments. In LPS-challenged THP-1 cells, VK3 attenuated the induction of selected inflammatory transcripts, indicating that effects beyond STING-agonist-stimulated signaling cannot be excluded. In mice, topical VK3 attenuated imiquimod (IMQ)-induced psoriasis-like skin inflammation, reduced IL-17 and IL-23 expression, and did not appreciably affect body weight or the measured organ indices. Among the vitamin K analogues examined, VK3 showed the most consistent attenuation of STING-agonist-induced signaling. These findings support further investigation of VK3 as a topical modulator of inflammatory signaling in skin disease. - Source: PubMed
Publication date: 2026/09/16
Jin ZuyiHuang ZhenZhang YiqinMeng MeichenHong LiangLi Min