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
- The cGAS-STING pathway plays a central role in antitumor innate immunity, but the therapeutic efficacy of STING agonists is often limited by insufficient tumor delivery and inadequate amplification of endogenous danger signals. Here, we developed a lactate oxidase-engineered manganese layered double hydroxide nanoplatform loaded with the STING agonist MSA-2, termed Mn-LDH-M@LOX, to establish a tumor metabolism-driven STING amplification strategy. Under mildly acidic tumor-associated conditions, Mn-LDH-M@LOX underwent structural disassembly and synchronously released manganese ions and MSA-2. Meanwhile, surface-immobilized LOX converted tumor-derived lactate into hydrogen peroxide, thereby providing an endogenous fuel for manganese-mediated ROS amplification. This cascade induced oxidative DNA damage, mitochondrial dysfunction and cytosolic mtDNA accumulation, which further reinforced cGAS-STING-related immune activation together with MSA-2 and manganese ions. In 4T1 tumor cells, Mn-LDH-M@LOX efficiently enhanced ROS generation, mitochondrial depolarization, γ-H2AX-associated DNA damage, ICD-related signals and downstream immune responses, including increased p-IRF3, IFN-β and CXCL10. In vivo, Mn-LDH-M@LOX significantly suppressed tumor growth, reduced intratumoral lactate content and decreased Ki67 expression, while promoting CRT exposure, dendritic cell maturation, CD4/CD8 T-cell infiltration and intratumoral cytokine/chemokine production. Moreover, no obvious systemic toxicity was observed based on body weight, blood biochemical indices, routine blood parameters and major organ histology. Overall, this work presents a lactate-fueled manganese nanocatalytic platform that converts tumor metabolic reprogramming into ROS-amplified STING activation, offering a promising strategy for enhanced tumor immunotherapy. - Source: PubMed
Publication date: 2026/08/14
Cai FengJiang DengshengGeng MingzheXu HongboSong ShilongWang GengmingHe ZelaiXu Lu - Elderly patients undergoing cardiac surgery are highly susceptible to postoperative pulmonary complications triggered by conventional extracorporeal circulation (CECC)-driven systemic inflammation and subsequent pulmonary endothelial injury. Minimally invasive extracorporeal circulation (MiECC) lowers perioperative hemodilution and systemic inflammatory load, yet the underlying intracellular protective mechanisms in aged populations remain incompletely understood. This study therefore aimed to delineate the C5a-mtDNA-cGAS-STING signaling cascade as the central pathway mediating MiECC's pulmonary protective effect. - Source: PubMed
Publication date: 2026/08/14
Zhao YunWang JiaxingYang ZhaohuaMa WenruiWang ChunshengWei LaiZhao DajunZhang Shutian - Inflammation exerts context-dependent influences on tumor progression and therapeutic response. Although chemotherapy remains a cornerstone of cancer treatment, its functional interplay with inflammatory signaling is still incompletely understood. Here, we identify TANK-binding kinase 1 (TBK1) as a critical modulator of chemotherapeutic efficacy through its impact on DNA damage repair. TBK1 activation potentiates cancer-cell death induced by chemotherapeutic agents by promoting DNA damage and impairing homologous recombination (HR) repair. This effect occurs independently of canonical inflammatory cytokines, as demonstrated in IRF3- and p65- double deficient cells. Mechanistically, TBK1 suppresses recruitment of the key HR factor Meiotic Recombination 11 Homolog 1 (MRE11) to PARP1 at DNA-damage sites in a kinase-activity-dependent yet cytokine-independent manner. Furthermore, TBK1 activation correlates with enhanced p53 signaling and genomic instability, providing a molecular basis for its pro-death effects under chemotherapy. Collectively, these findings reveal a previously unrecognized function of TBK1 in modulating the DNA-damage response, linking inflammatory signaling to genome destabilization and identifying the TBK1-MRE11 axis as a potential target to enhance chemotherapeutic efficacy. - Source: PubMed
Publication date: 2026/08/14
Zhou WeiWang XiangyuSteigleder Susanne SXing AoweiYang DanLi ZhuoyueLiu HongjiZhang YuxinWang WenjingShen FeiyangTang YihanDeng LinJiang Hui - Head and neck squamous cell carcinoma (HNSCC) remain a major clinical challenge due to its high heterogeneity and limited therapeutic response, resulting in a 5-year overall survival rate of only ~50%. Identifying molecular pathways that drive tumor progression while suppressing anti-tumor immunity is therefore critical for developing more effective therapies. N-acetyltransferase 10 (NAT10) is the only known enzyme responsible for catalyzing the RNA modification N4-acetylcytidine (ac4C) on rRNA, tRNA, and mRNA, and has been implicated in tumor progression in several cancers. In this study, we identify NAT10 as a key suppressor of tumor-intrinsic immune signaling in HNSCC. NAT10 expression was significantly elevated in tumor tissues and HNSCC cell lines and was associated with poor overall survival. Moreover, high-risk HPV, a major etiological factor in HNSCC, upregulated NAT10 protein expression through the viral oncoproteins E6 and E7. Functional inhibition of NAT10, either by genetic depletion or the small-molecule inhibitor Remodelin, activated tumor-intrinsic innate immune responses, as evidenced by increased IRF3 phosphorylation and induction of type I/II interferons and interferon-stimulated genes. Depletion of NAT10 was able to suppress tumorigenic phenotypes, including cell proliferation, migration, and colony formation in HNSCC cells. Importantly, activation of the STING signaling pathway using agonist cyclic di-GMP further amplified immune activation in NAT10-inhibited cancer cells. Together, our findings establish NAT10 as a previously unrecognized negative regulator of tumor-intrinsic immunity in HNSCC and support NAT10 targeting, particularly in combination with STING agonists, as a promising immunotherapeutic strategy. - Source: PubMed
Publication date: 2026/08/08
Lepcha Thurbu TsheringParuchuri NithyaZhou DaweiFiches Guillaume NHe JinshanShanaka K A S NLiu YanEleya SuhaKoirala NischalZhu JianMitchell DarrionZhao John WSantoso Netty G - The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is an essential cytosolic DNA-sensing system that plays an important role in the regulation of innate immune and inflammatory responses in the central nervous system (CNS). It was first discovered as a promising antiviral defense cascade and has since been shown to execute broader functions in neuroinflammation and neurodegeneration. The pathway can become hyperactive with the release of endogenous DNA from damaged nuclei, mitochondria, or genomic instability, leading to chronic production of type I interferon (TI-IFN), various pro-inflammatory cytokines, and eventually contributing to chronic neuroinflammatory diseases. Recent studies have found that dysregulated cGAS-STING signaling is associated with several neurological disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), traumatic brain injury (TBI), stroke, and age-related neurodegeneration. In the CNS, chronic activation of this pathway leads to activation of microglia, oxidative stress, breakdown of the blood-brain barrier (BBB), impaired function of the synapses, and neuronal death. Mitochondrial dysfunction and cytosolic release of mitochondrial DNA (mtDNA) further promote inflammatory signaling, thus perpetuating neurodegeneration. This review highlights the molecular and pathological mechanisms of cGAS-STING signaling in a broader aspect of neurological disorders and appraises the novel therapeutics already under development to inhibit this pathway to regulate neuroinflammation and enhance neurological outcomes. - Source: PubMed
Publication date: 2026/08/12
Rahim AbdulZubair Shaik MahammadAhamed MustakDas SoumiPatel RoyalDebnath BiplabPorel Pratyush