IRF1 Pre-design Chimera RNAi
- Known as:
- IRF1 Pre-design Chimera RNAi
- Catalog number:
- H00003659-R01
- Product Quantity:
- 10 nmol
- Category:
- -
- Supplier:
- Abno
- Gene target:
- IRF1 Pre-design Chimera RNAi
Related genes to: IRF1 Pre-design Chimera RNAi
- Gene:
- IRF1 NIH gene
- Name:
- interferon regulatory factor 1
- Previous symbol:
- -
- Synonyms:
- MAR
- Chromosome:
- 5q31.1
- Locus Type:
- gene with protein product
- Date approved:
- 1991-05-09
- Date modifiied:
- 2016-10-05
Related products to: IRF1 Pre-design Chimera RNAi
Related articles to: IRF1 Pre-design Chimera RNAi
- PANoptosis is a newly described type of cell death that can be triggered upon microbial infection, autoinflammatory diseases, and cytokine storms, and involves the coordinated activation of pyroptosis, apoptosis, and necroptosis. Pseudorabies virus (PRV) infection has been reported to trigger excessive inflammatory responses in mice, swine, and in rare cases in humans, leading to acute viral encephalitis. However, the precise mechanisms by which PRV exacerbates host inflammation responses remain incompletely understood, and the potential role of PANoptosis in this pathogenic process has yet to be elucidated. Here, we demonstrate that PRV infection in different cell lines, murine primary macrophages and mice all results in activation of the PANoptotic signaling pathway and drives the formation of the core scaffold (caspase-8/ASC/RIPK3) within the PANoptosome. We observe that innate sensor proteins AIM2, Pyrin, and ZBP1 interact with the core scaffold protein ASC in PRV-infected THP-1 Mφ and co-localize with ASC. We further identify that IRF1 serves as the key transcription factor that is upregulated during PRV infection. Increased IRF1 translocates to the nucleus and binds directly to the promoter regions of innate sensor genes ZBP1 and AIM2, thereby elevating their gene expression. Ultimately, we discover that the genetic suppression of IRF1 expression and pharmacological blockade of PANoptosis markedly attenuate the extracellular release of pro-inflammatory mediators HMGB1 and IL-1β during PRV infection in vitro. Moreover, pharmacological inhibition of PANoptosis in vivo substantially reduces levels of HMGB1 and IL-1β in cerebral tissue of PRV-infected mice and effectively confers significant protection against PRV challenge, supporting an important role for PANoptosis in PRV pathogenesis. Collectively, our study not only provides a novel perspective on the pro-inflammatory mechanisms of PRV but also highlights that PANoptosis may be therapeutically targeted to improve viral infection outcomes. - Source: PubMed
Publication date: 2026/06/05
Yu LiangzhengChen YueZhu ZhenbangFavoreel Herman WLi Xiangdong - Multiple Myeloma (MM), the second most prevalent hematologic malignancy, remains incurable, highlighting the need to identify molecular drivers of disease progression and new therapies. Using a CRISPR-Cas9 library screening approach in MM cells, we identified 22 essential transcription factors (TFs), including members of the interferon regulatory factor (IRF) family. Remarkably, in addition to the well-known IRF4, IRF2 emerged as a critical TF in MM. Cut&Run experiments demonstrated that IRF2 binds extensively to chromatin, both independently and in cooperation with IRF1 and IRF4. While IRF2-unique regions were predominantly associated with active promoters, regions bound by IRF2/1/4 were biased towards introns. Functionally, IRF2 contributes to MM cell survival by suppressing necroptosis and promoting cell migration. Notably, IRF2-dependent transcriptional dysregulation was evident in precursor conditions such as MGUS and SMM, suggesting a role in early disease evolution. In addition to its role as early factor, IRF2 levels also seem to influence disease progression, as MMs with higher expression showed worse progression-free survival (PFS) and overall survival (OS) in both univariate and multivariate analyses, even after adjusting for common MM genetic risk factors. In conclusion, IRF2 constitutes an underappreciated essential TF involved in the pathogenesis and clinical behavior of MM. Its inhibition leads to dysregulation of key signaling pathways in MM pathogenesis, highlighting its potential as a therapeutic target. - Source: PubMed
Publication date: 2026/03/12
Gómez-Echarte NahiaCarrasco-Leon ArantxaMaiques-Diaz AlbaBarrena NaroaMiranda EstibalizGarate LeireAmundarain AneSan Martín-Úriz PatxiCharalampopoulou StellaValcárcel Luis VAriceta BeñatRodriguez-Marquez PaulaRodriguez-Madoz Juan RobertoIshiguro KazuyaPlanes Francisco JRodriguez-Otero PaulaMitsiades Constantine SMartín-Subero José-IgnacioSan-José Enériz EdurneProsper FelipeAgirre Xabier - Interferon regulatory factor 1 (IRF1) has long been recognized as a tumor suppressor; however, recent studies have revealed context-specific and sometimes opposing roles in cancer progression. Here, we describe a T cell-specific mechanism underlying the antitumor activity of IRF1. Unlike germline -deficient mice, T cell-specific loss of IRF1 does not lead to a deficiency in cytotoxic CD8⁺ T cells. Nevertheless, tumor burden remains elevated in these mice, associated with reduced CD8⁺ T cell infiltration driven by impaired activation and proliferation in the absence of IRF1. Transcriptomic analysis of activated -deficient T cells identified NFATc1 as a key gene significantly downregulated upon IRF1 loss. Analysis of human melanoma datasets further corroborated this finding, highlighting a previously unappreciated role for IRF1 in regulating T cell activation and antitumor immunity. - Source: PubMed
Publication date: 2026/05/18
Shao LuluBannerjee HrideshUnal EcemMehta IshaDas JishnuBanday A RoufKane LarrySarkar Saumendra N - Type 1 diabetes (T1D) is characterized by the autoimmune destruction of pancreatic beta cells. While most beta cells are lost, a subset of beta cells persists years and even decades after disease onset. Studying these surviving cells is challenging, and thus how they escape immune killing remains poorly understood. Here, we applied a gene regulatory network inference-based clustering approach on existing islet scRNAseq data from cadaveric donors with T1D, autoantibody positive donors at risk for T1D, and non-diabetic donors to analyze beta cells from patients with established T1D. This approach identified a novel beta cell subtype enriched in T1D donors defined by the activity of several transcription factors which have well-characterized roles in beta cell survival, most notably IRF1. We found increased expression of immunomodulatory genes (e.g. ) as well as decreased expression of autoantigens and secretory genes, suggesting dedifferentiation. We identified inflammatory cytokines as a driver of this phenotype by reanalyzing public data from primary human beta cells stimulated with inflammatory cytokines in vitro. We additionally find a similar transcriptional program active in a subset of alpha cells, consistent with cell-extrinsic inflammatory cytokine signaling in vivo. Overall, we propose that this population represents a resilient beta cell phenotype, and that the transcriptional program active in these cells may identify targets for T1D prevention and reversal. - Source: PubMed
Publication date: 2026/05/27
Spurrell MaxwellTsang John SHerold Kevan C - Hepatic ischemia-reperfusion injury (IRI) is a complex event influenced by interconnected immune and metabolic processes. Steatotic livers are especially sensitive to IRI, but the crosstalk between innate inflammatory responses and lipid metabolic dysregulation in this context is not well understood. Using transcriptomic profiling in a murine high-fat diet (HFD) model, we assessed immune and metabolic responses to hepatic IRI and examined the effects of N-acetylcysteine (NAC). In steatotic livers, IRI induced the upregulation of inflammatory mediators, including TLR/NF-κB-associated genes (, , ) and neutrophil-associated genes (, ), accompanied by the downregulation of lipid and cholesterol metabolism-related genes, including , , , and . NAC supplementation attenuated inflammatory gene expression and restored key lipid biosynthetic regulators. We then performed targeted lipidomic analysis to determine whether NAC-mediated transcriptional changes were reflected at the lipid level and observed a significant increase in total phosphatidylcholine and sphingomyelin in steatotic livers following IRI. Finally, to assess the contribution of innate immune cells to hepatic IRI, we quantified neutrophils and macrophages in HFD+NAC IRI and HFD IRI livers. We found that NAC supplementation reduced hepatic neutrophil accumulation and markedly decreased LCN2 expression following IRI. - Source: PubMed
Publication date: 2026/05/19
Kang JimanPatil DigvijayHackett RyanCui YukiOza KeshaRutkowski AbigailLiggett Jedson RLi HenghongRanjit SumanKwon DongHyangKallakury BhaskarAlbanese ChrisGondolesi Gabriel EEkong UdemeCui WanxingKhan KhalidFishbein Thomas MKroemer Alexander