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Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by an overactive immune response, particularly involving excessive production of type I interferons. This overproduction is driven by the phosphorylation of IRF7, a crucial factor in interferon gene activation. Current treatments for SLE are often not very effective and can have serious side effects.
Methods: Our study introduces clobenpropit, a histamine analogue, as a potential new therapy targeting the CXCR4 receptor to reduce IRF7 phosphorylation and subsequent interferon production. We employed various laboratory techniques to investigate how clobenpropit interacts with CXCR4 and its effects on immune cells from healthy individuals and SLE patients.
Results: Clobenpropit binds effectively to CXCR4, significantly inhibiting IRF7 phosphorylation and reducing interferon production. Additionally, clobenpropit lowered levels of pro-inflammatory cytokines in a mouse model of lupus, demonstrating efficacy comparable to the standard treatment, prednisolone.
Discussion: These results suggest that clobenpropit could be a promising new treatment for SLE, offering a targeted approach with potential advantages over current therapies.
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http://dx.doi.org/10.3389/fimmu.2024.1490593 | DOI Listing |
Genes Immun
September 2025
Institut Pasteur, Université Paris Cité, Mouse Genetics Laboratory, Paris, France.
Interferon regulatory factor 3 (IRF3) is the first transcription factor activating the expression of type I interferons (IFN-I). It is present in the cytoplasm of most cell types under basal conditions and its activation by phosphorylation allows a rapid triggering of the IFN-I pathway in response to viral infection. This activation of IFN-I is amplified by IRF7, the other major IFN-I transcription factor which expression is induced, in most cell types, by the interferon response.
View Article and Find Full Text PDFPoult Sci
August 2025
Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, China; Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, and Key Lab of Chicken Genetics, Breeding and Reproduction, Minis
Avian leukosis viruses (ALVs) are a group of retroviruses with immunosuppressive and tumorigenic effects, causing substantial economic losses to the poultry industry due to the lack of effective commercial vaccines and antiviral drugs. Granulocyte colony-stimulating factor 3 (CSF3) is a cytokine that regulates hematopoiesis and modulates the proliferation and differentiation of immune cells. In our previous study, we unexpectedly observed that CSF3 expression was significantly upregulated upon stimulation with interferon-α (IFN-α) and ALV, suggesting a potential role in ALV infection.
View Article and Find Full Text PDFJ Virol
August 2025
Ministry of Education Key Lab for Avian Preventive Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China.
Unlabelled: Cyclic GMP-AMP synthase (cGAS) recognizes viral DNA within the cytoplasm and initiates innate antiviral response through the cGAS-STING pathway. However, viruses have evolved diverse strategies to counteract the cGAS-STING signaling pathway. Avian leukosis virus subgroup J (ALV-J), an avian oncogenic retrovirus, can antagonize host innate immune responses and cause immunosuppression to develop tumors.
View Article and Find Full Text PDFDiabetes Metab Syndr Obes
July 2025
Department of Nephrology, The Second Hospital Affiliated to Kunming Medical University, Kunming, People's Republic of China.
Background: Chronic kidney disease (CKD) and diabetic nephropathy (DN) represent significant renal health challenges, with overlapping pathogenic mechanisms. This study evaluated shared biomarkers in CKD and DN through single-cell sequencing, aiming to identify potential diagnostic and therapeutic targets and provide new insights into their common pathogenesis.
Methods: In this study, single-cell RNA sequencing was performed on nine columns of human blood samples, including three control cases, three CKD cases, and three DN cases.
bioRxiv
July 2025
Department of Cell and Biological Systems, Penn State College of Medicine, Hershey, Pennsylvania, USA.
Aryl hydrocarbon receptor (AhR) interacting protein (AIP) suppresses type I IFN production by interacting with and preventing the nuclear translocation of the transcription factor IRF7. The kinase TBK1 phosphorylates AIP to promote IRF7 binding and the inhibition of the type I interferon (IFN) response. However, it is unknown if AIP expression in innate immune cells is important to suppress type I IFN in the context of RNA virus infection and .
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