Ask about this productRelated genes to: IFNa4 protein (Mouse)
- Gene:
- IFNA4 NIH gene
- Name:
- interferon alpha 4
- Previous symbol:
- -
- Synonyms:
- MGC142200, IFN-alpha4a
- Chromosome:
- 9p21.3
- Locus Type:
- gene with protein product
- Date approved:
- 1993-01-14
- Date modifiied:
- 2016-10-05
Related products to: IFNa4 protein (Mouse)
Related articles to: IFNa4 protein (Mouse)
- Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection first emerged in Wuhan, Hubei Province, China, in December 2019 and spread rapidly to other provinces and other countries. Angiotensin I converting enzyme 2 (ACE2) is the receptor for SARS-CoV and has been suggested to be also the receptor for SARS-CoV-2. Paradoxically, ACE2 expression in the lung protects mice from SARS-CoV spike protein induced lung injury by attenuating the renin-angiotensin system. In the intestine, ACE2 also suppresses intestinal inflammation by maintaining amino acid homeostasis, antimicrobial peptide expression and ecology of the gut microbiome. We performed analysis of single cell-RNA sequencing data from control subjects and those with colitis or inflammatory bowel disease (6 controls, 6 colitis cases, 2 ulcerative colitis cases and 3 Crohn's disease cases). The single cell-RNA sequencing data was also used to conduct co-expression analysis and GO enrichment analysis. Multiplex immunofluorescence (mIF) was performed to assess the expression of ACE2, IFNA4, and RSAD2 on colon specimens obtained from patients, including non‑diseased (control) tissue, ulcerative colitis (UC) tissue and Crohn's disease (CD) tissue. We revealed that ACE2 exhibited specific and high expression levels in colonocytes. Furthermore, genes implicated in viral infection and anti-infection immunity were also found to be highly expressed in colonocytes. Additionally, we conducted an analysis of genes co-expressed with ACE2 within colonocytes, and total of 3420 and 2136 genes were identified as being positively and negatively correlated with ACE2 expression. Concurrently, through Gene Ontology (GO) enrichment analysis, it was observed that genes positively associated with ACE2 expression were significantly enriched in pathways related to viral infection, organismal immunity, and energy metabolism. Accordingly, mIF showed a significant increase in IFNA4 and RSAD2 expression in the colonic epithelial ACE2⁺ cells of UC and CD patients relative to controls. Integrated data from single cell-RNA sequencing and patient's mIF highlighted the expression profile of ACE2 in colonic epithelial cells, suggesting the possible involvement of ACE2 in the intestinal tract of patients with SARS-CoV-2 pneumonia in enteroviral infection, immunity and energy metabolism functions. - Source: PubMed
Publication date: 2026/01/19
Qi YuyinHuang YuxinChen HanhanLi JieLiu MingXiong WenjingTang QinZhang Yuxia - Multiple sclerosis (MS) is a chronic neurodegenerative disorder for which dysregulated ferroptosis and necroptosis have demonstrated pathological associations but these lack causal validation in disease susceptibility. This study employed proteome-wide Mendelian randomization (MR) to investigate causal links between ferroptosis/necroptosis pathways, their upstream regulators, immune interactions, and MS risk. Transcriptomic validation utilized bulk RNA-seq and single-cell RNA-seq data. MR identified IFNA4 (OR = 0.24) and TNFAIP3 (OR = 2.0) as key causal ferroptosis/necroptosis-related proteins for MS risk. Analysis revealed 15 upstream regulators significantly associated with MS (FDR < 0.05; e.g., GZMA, CXCL3, APOE, CFB, CA6, KIR2DL2/3). Transcriptomic validation consistently identified ceruloplasmin (CP) as upregulated in MS microglia and lesions. Mediation analyses established two complete causal pathways: an IFNA4-mediated pathway wherein five upstream immune regulators (KIR2DL2, KIR2DL3, CFB, GZMA, and CA6) influence MS susceptibility through IFNA4 regulation, with all component effects statistically significant; and an APOE-driven pathway operating via TNFAIP3, demonstrating significant total effects and near-significant mediator-outcome effects on MS risk. While 59 immune traits were MS-associated, only TNFAIP3 showed a suggestive association with CD27⁺ memory B cells. This study establishes ferroptosis/necroptosis pathways as causal drivers of MS susceptibility, highlighting TNFAIP3, IFNA4, CP, and APOE as therapeutically actionable targets. - Source: PubMed
Publication date: 2025/12/12
Yan WuJianhong WangWen JiangLinming Zhang - STING1 is a central hub protein of CGAS-STING1 signaling which is important signaling axis to sense DNA for the host against pathogens infection through regulating type I interferon (IFN-I) production. However, excessive STING1 activation-induced overproduced IFN-I triggers tissue damage and autoimmune disorders. Thus, the activity of STING1 must be precisely regulated for immune homeostasis. Here, we discovered SESN1 (sestrin 1) as an essential negative regulator of STING1 to maintain immune homeostasis. Upon herpes simplex virus-1 (HSV-1) infection, the expression of SESN1 was downregulated, which enhanced potentiality to virus defense for host. Consistently, SESN1-deficient mice exhibited stronger ability against HSV-1 infection compared to wild-type littermates. Additionally, we found the expression of SESN1 was decreased in systemic lupus erythematosus (SLE) patients and KO mouse model of autoimmune disease. Intriguingly, the replenishment of SESN1 effectively impressed IFN-I production and autoimmune responses in the PBMCs of human SLE specimens and the KO mouse model both and . Mechanistically, SESN1 targeted STING1 and promoted STING1 autophagic degradation by facilitating the interaction of SQSTM1/p62 and STING1. Together, our study uncovers a crucial role of SESN1 for immune homeostasis to balance anti-virus and autoimmunity by regulating STING1. SESN1 might be a potential therapeutic target for infectious and autoimmune diseases.: BMDMs: bone marrow-derived macrophages; cGAMP: cyclic GMP-AMP; CGAS: cyclic GMP-AMP synthase; HTDNA: herring testes DNA; IFNA4: interferon alpha 4; IFNB: interferon beta; IRF3: interferon regulatory factor 3; ISD: interferon stimulatory DNA; ISGs: IFN-stimulated genes; PBMCs: peripheral blood mononuclear cells; RSAD2: radical S-adenosyl methionine domain containing 2; SLE: systemic lupus erythematosus; STING1: stimulator of interferon response cGAMP interactor 1; TBK1: TANK binding kinase 1. - Source: PubMed
Publication date: 2025/02/13
Xu LingxiaoZhang HongqianQiu ZuochengWang ShijingWang ChaoyangCheng HaoWan QianyaPan Mingyu - Plasmacytoid dendritic cells produce large amounts of type-I interferon (IFN-I) upon sensing nucleic acid components of pathogens by Toll-like receptors (TLR7 and TLR9). The transcription factor Spi-B has the DNA-binding Ets domain, and transactivates the Ifna4 promoter co-operatively with IFN regulatory factor-7 (IRF-7) for TLR7/TLR9-induced IFN-I production. Spi-B associates with IRF-7, and activates transcription by binding to the 5'-AGAA-3' sequence, being different from 5'-GGAA-3', known as the Ets domain recognition sequence. To understand the molecular mechanism for the co-operative transactivation of the Ifna4 promoter by Spi-B and IRF-7, we performed X-ray structural determination of the Spi-B Ets domain in complex with target DNAs, including 5'-AGAA-3' and 5'-GGAA-3' sequences. Furthermore, we conducted a modeling study of the complex of the Spi-B and IRF-7 with Ifna4 promoter DNA. X-ray structures showed that the binding of the Spi-B Ets domain induces a kink in DNA at the recognition sequence, and a more kinked DNA structure was observed in 5'-AGAA-3' than 5'-GGAA-3'. A modeling study showed that the Spi-B-induced kinked DNA structure in 5'-AGAA-3' is favorable for Spi-B and IRF-7 to approach each other for association on DNA. - Source: PubMed
Publication date: 2025/01/17
Nonaka YasuhiroHoshino KatsuakiNakamura TakanoriKamitori Shigehiro - STING1 (stimulator of interferon response cGAMP interactor 1) is the quintessential protein in the CGAS-STING1 signaling pathway, crucial for the induction of type I IFN (interferon) production and eliciting innate immunity. Nevertheless, the overactivation or sustained activation of STING1 has been closely associated with the onset of autoimmune disorders. Notably, the majority of these disorders manifest as an upregulated expression of type I interferons and IFN-stimulated genes (ISGs). Hence, strict regulation of STING1 activity is paramount to preserve immune homeostasis. Here, we reported that CSNK1A1/CK1α, a serine/threonine protein kinase, was essential to prevent the overactivation of STING1-mediated type I IFN signaling through autophagic degradation of STING1. Mechanistically, CSNK1A1 interacted with STING1 upon the CGAS-STING1 pathway activation and promoted STING1 autophagic degradation by enhancing the phosphorylation of SQSTM1/p62 at serine 351 (serine 349 in human), which was critical for SQSTM1-mediated STING1 autophagic degradation. Consistently, SSTC3, a selective CSNK1A1 agonist, significantly attenuated the response of the CGAS-STING1 signaling by promoting STING1 autophagic degradation. Importantly, pharmacological activation of CSNK1A1 using SSTC3 markedly repressed the systemic autoinflammatory responses in the mouse autoimmune disease model and effectively suppressed the production of IFNs and ISGs in the PBMCs of SLE patients. Taken together, our study reveals a novel regulatory role of CSNK1A1 in the autophagic degradation of STING1 to maintain immune homeostasis. Manipulating CSNK1A1 through SSTC3 might be a potential therapeutic strategy for alleviating STING1-mediated aberrant type I IFNs in autoimmune diseases. BMDMs: bone marrow-derived macrophages; cGAMP: cyclic GMP-AMP; CGAS: cyclic GMP-AMP synthase; HTDNA: herring testes DNA; IFIT1: interferon induced protein with tetratricopeptide repeats 1; IFNA4: interferon alpha 4; IFNB: interferon beta; IRF3: interferon regulatory factor 3; ISD: interferon stimulatory DNA; ISGs: IFN-stimulated genes; MEFs: mouse embryonic fibroblasts; PBMCs: peripheral blood mononuclear cells; RSAD2: radical S-adenosyl methionine domain containing 2; SLE: systemic lupus erythematosus; STING1: stimulator of interferon response cGAMP interactor 1; TBK1: TANK binding kinase 1. - Source: PubMed
Publication date: 2024/01/25
Pan MingyuHu TongyuLyu JiaoYin YueSun JingWang QuanyiXu LingxiaoHu HaiyangWang Chen