Ask about this productRelated genes to: IRF3 protein
- 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 protein
Related articles to: IRF3 protein
- - Source: PubMed
Publication date: 2026/04/28
Asadpour AtiyehOzsoy NagihanNapier LeahCox KathrynNeeds SarahTaylor Kirk ABrown HelenPivoriūnas AugustasStephens PhilDash PhilCottrell Graeme SWidera Darius - Both regulatory B (B) and myeloid cells in tumors and lymph nodes drive immune suppression in pancreatic cancer. Current strategies to counter immune suppression emphasize myeloid cells but overlook B cells. We discovered that STING agonist expanded B cells depended on PI3Kγ but not PI3Kδ in pancreatic cancer, whereas activating myeloid cells were independent of PI3Kγ. Inhibition of PI3Kγ, but not PI3Kδ, decreased STING-induced IRF3 phosphorylation and B cell expansion in pancreatic cancer, while sustaining STING-induced IRF3 phosphorylation to activate myeloid cells. We developed a dual targeting compound and its albumin nanoformulation Nano-273, which stimulated STING to activate myeloid cells and inhibited PI3Kγ to decrease STING-induced B cell expansion. Nano-273 delivered the drug to tumors and lymph nodes to overcome myeloid cell- and B cell-mediated immune suppression in pancreatic cancer. Nano-273, combined with anti-programmed cell death protein 1, achieved durable efficacy in transgenic KPC mice with pancreatic cancer, offering potential for pancreatic cancer treatment. - Source: PubMed
Publication date: 2026/04/28
Li ChengyiKe FangZhao HongyiMao ShuaiDjibo MahamadouHuang LinqiHe MiaoWang MeilinWen HanningLiu ZhongweiYu ZhixinQi ZhihongXavier Ana RNenwani MinalWen BoPeterson NicoleSahai VaibhavNagrath DeepakLucas Carrie LWymann Matthias PGao WeiFong LawrenceSun Duxin - Overactive stimulator of interferon gene (STING) signaling drives inflammatory and autoimmune diseases, making STING inhibition a promising therapeutic strategy. However, the complex binding mechanisms and limited structural diversity hinder the development of STING inhibitors. In this study, we identified a small-molecule STING inhibitor, Y-320, via cell-based screening. It binds STING with nanomolar affinity and potently inhibits STING-mediated interferon signaling in human and mouse cells. Mechanistically, Y-320 blocks the Golgi translocation and phosphorylation of STING, preventing interferon regulatory factor 3 (IRF3) recruitment. Notably, Y-320 allosterically targets the non-canonical transmembrane domain (TMD) pocket without competing with the endogenous agonist 2'3'-cGAMP by engaging residues Y46 and W119 in the transmembrane helices 2 and 4. Importantly, Y-320 alleviated cisplatin-induced acute kidney injury in mice in a STING-dependent manner. This work not only reveals an additional mechanism underlying the regulatory complexity of STING but also provides a TMD-targeted allosteric STING inhibitor with demonstrated efficacy in both in vitro and in vivo models. - Source: PubMed
Publication date: 2026/04/27
Chen QingxuanShen AnchengShi XinyiLin TailiangWang QinghuaWang ZhenYu XuekuiMa BuyongDing ChunyongZhang Ao - Malathion (MAL) exerts serious reproductive toxicity in males and leads to histopathological injuries in seminiferous tubules, sperm abnormalities, and hormonal disruptions such as reduced testosterone levels. The study assessed whether Lactobacillus acidophilus (L. acidophilus) supplementation could mitigate MAL-induced testicular damage via the crosstalk of cGAS/cGAMP/STING/NF-κB signaling, which in turn modulates the inflammatory cascades IRF3/IFN-β and TNFR/TNF-α, as well as the autophagic markers such as LC3-B/p62. The study also studied the role of miRNA-24 as an upstream regulator. The study included four groups: control, MAL-intoxicated group, L. acidophilus- and scopolamine-treated group. Seminal analysis and histopathological investigations of the testes were done. cGAS, STING, TNFR, IRF3, and miR-24 were estimated using qRT-PCR. cGAMP, IFN-β, LC3-B, and p62 were estimated using ELISA, whereas NF-κB and TNF-α were estimated using immunohistochemical analysis. MAL-intoxicated group showed altered seminal fluid analysis, higher gene expression of cGAS, STING, TNFR, and IRF3, along with lower gene expression of miRNA-24 compared with the control group. Moreover, the concentrations of cGAMP and IFN-β were higher, along with lower concentrations of testosterone, LC3-B, and p62, compared with the control group. Furthermore, NF-κB and TNF-α showed marked positive cytoplasmic expression. However, the L. acidophilus-treated group reversed all the above-mentioned findings. Collectively, the present study showed that MAL-exposure induces testicular toxicity via activating the cGAS/cGAMP/STING/IRF3/NF-κB/TNF-α axis, mediated by miRNA-24. L. acidophilus treatment alleviated these adverse effects, not only by restoring sperm quality, hormonal balance, and tissue architecture but also by suppressing the inflammatory signaling cascade, reactivating autophagic flux, and upregulating protective miRNA-24. - Source: PubMed
Abd-Elmawla Mai AEl Magdoub Hekmat MAboulmagd Yara MEl-Mahdy Safaa MDessouky NesrineAborehab Nora M - Natural products are biologically active compounds used for therapeutic interventions for various diseases, particularly infections. Autophagy is an intracellular catabolic pathway involving lysosomal degradation and is closely associated with immunological pathways, effectively combating bacterial, viral, fungal, and parasitic infections. Accumulating evidence suggests that autophagy activation or inhibition by natural products promotes antimicrobial responses against various pathogens. Numerous natural products can modulate autophagy through diverse signaling pathways, suggesting their potential as a host-directed therapeutic strategy that may complement conventional drug regimens or help mitigate drug resistance in various infectious diseases. However, it remains largely unclear whether these effects are mediated by direct modulation of autophagy or indirectly through associated mechanisms, including enhanced immune defense, attenuation of pathological inflammation, or crosstalk with other organelle functions. Additionally, multiple pathogens can evade host responses; thus, autophagy activation may inadvertently create favorable conditions for certain pathogens. This review discusses the current knowledge of natural products in terms of their antimicrobial actions through autophagy regulation, particularly the roles of distinct natural product classes, such as polyphenols, alkaloids, terpenoids, quinones, peptides, and macrolides in modulating autophagy for potentially contributing to control various infectious diseases. Exploring the intricate molecular interplay between natural products and autophagy in limiting infections may provide valuable insights that could inform the development of innovative host-directed antimicrobial treatments based on autophagy regulation. 3-MA: 3-methyladenine; AM: alveolar macrophages; AMP: antimicrobial peptides; AMPK: 5' adenosine monophosphate-activated protein kinase; ARDS: acute respiratory distress syndrome; ART: artemisinin; ASFV: African swine fever virus; ATG: autophagy related; AZM: azithromycin; BafA1: bafilomycin A; BECN1: beclin 1; BMDM: bone marrow-derived macrophage; BNIP3: BCL2 interacting protein 3; BNIP3L: BCL2 interacting protein 3 like; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CAMKK2: calcium/calmodulin-dependent protein kinase kinase 2; CBD: cannabidiol; CF: cystic fibrosis; CGA: chlorogenic acid; CGAS: cyclic GMP-AMP synthase; CHUK/IKKα: component of inhibitor of nuclear factor kappa B kinase complex; CLP: cecal ligation and puncture; CLR: clarithromycin; CMA: chaperone-mediated autophagy; CoV: coronavirus; DHT: dihydrotanshinone I; EGCG: epigallocatechin-3-gallate; EIF2A: eukaryotic translation initiation factor 2A; EIF2AK2: eukaryotic translation initiation factor 2 alpha kinase 2; ESKAPE: , and spp.; ESRRA: estrogen related receptor alpha; FOXO1: forkhead box O1; FUNDC1: FUN14 domain containing 1; HBV: hepatitis B virus; HCV: hepatitis C virus; HDT: host-directed therapy; HIV: human immunodeficiency virus; HMGB1: high mobility group box 1; HSV: herpes simplex virus; IAV: influenza A virus; ICT: isocryptotanshinone; IFN: interferon; IKBKB/IKKβ: inhibitor of nuclear factor kappa B kinase subunit beta; IL: interleukin; INH: isoniazid; IRF3: IFN regulatory factor 3; KEAP1: kelch like ECH associated protein 1; LAMP: lysosomal associated membrane protein; LAP: LC3-associated phagocytosis; LPS: lipopolysaccharide; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAPK: mitogen-activated protein kinase; MDM: monocyte-derived macrophage; MDR: multidrug-resistant; MON: monotropein; Mtb: ; MTOR: mechanistic target of rapamycin kinase; mtROS: mitochondrial ROS; NET: neutrophil extracellular trap; NFE2L2/Nrf2: NFE2 like bZIP transcription factor 2; NFKB/NF-κB: nuclear factor kappa B; NLRP3: NLR family pyrin domain containing 3; NLRX1: NLR family member X1; NOTCH1: notch receptor 1; NTM: nontuberculous mycobacteria; OMS: ohmyungsamycin; PAK1: p21 (RAC1) activated kinase 1; PINK1: PTEN induced kinase 1; PKM/PKM2: pyruvate kinase M1/2; PLD: phospholipase D; PM: peritoneal macrophage; PPM1A: protein phosphatase, Mg2+/Mn2+ dependent 1A; PRKN/parkin: parkin RBR E3 ubiquitin protein ligase; PtdIns3K: phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate; PTEN: phosphatase and tensin homolog; RB1CC1/FIP200: RB1 inducible coiled-coil 1; RELA/p65: RELA proto-oncogene, NF-kB subunit; RIF: rifampicin; ROS: reactive oxygen species; RSV: resveratrol; RUBCN/rubicon: rubicon autophagy regulator; SAR: selective autophagy receptor; SIRT: sirtuin; STING1: stimulator of interferon response cGAMP interactor 1; STX17: syntaxin 17; Tat: trans-activator of transcription; TB: tuberculosis; TBK1: TANK binding kinase 1; TFEB: transcription factor EB; TLR: toll like receptor; TNA: tanshinone IIA; TNF: tumor necrosis factor; UA: ursolic acid; ULK1/Atg1: unc-51 like autophagy activating kinase 1; UPR: unfolded protein response; UVRAG: UV radiation resistance associated; VAMP8: vesicle associated membrane protein 8; VDR: vitamin D receptor; WIPI2: WD repeat domain, phosphoinositide interacting 2; ZFYVE1/DFCP1: zinc finger FYVE-type containing 1; ZIKV: Zika virus. - Source: PubMed
Publication date: 2026/04/28
Paik SeungwhaUm SoohyunKim In SooPark Eun-JinKim Kyung TaeBasu JoyotiOh Dong-ChanJo Eun-Kyeong