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• W2591994964 abstract "Interleukin-1 receptor-associated kinase (IRAK) 4 mediates host defense against infections. As an active kinase, IRAK4 elicits full spectra of myeloid differentiation primary response protein (MyD) 88-dependent responses, while kinase-inactive IRAK4 induces a subset of cytokines and negative regulators whose expression is not regulated by mRNA stability. IRAK4 kinase activity is critical for resistance against Streptococcus pneumoniae, but its involvement in autoimmunity is incompletely understood. In this study, we determined the role of IRAK4 kinase activity in murine lupus. Lupus development in BXSB mice expressing the Y chromosome autoimmunity accelerator (Yaa) increased basal and Toll-like receptor (TLR) 4/7-induced phosphorylation of mitogen-activated protein kinases, p65 nuclear factor-κB (NF-κB), enhanced tumor necrosis factor (TNF)-α and C-C motif chemokine ligand (CCL) 5 gene expression in splenic macrophages, but decreased levels of Toll-interacting protein and IRAK-M, without affecting IRAK4 or IRAK1 expression. Mice harboring kinase-inactive IRAK4 on the lupus-prone Yaa background manifested blunted TLR signaling in macrophages and reduced glomerulonephritis, splenomegaly, serum anti-nuclear antibodies, numbers of splenic macrophages, total and TNF-α+ dendritic cells, activated T- and B-lymphocytes, and lower TNF-α expression in macrophages compared with lupus-prone mice with functional IRAK4. Thus, IRAK4 kinase activity contributes to murine lupus and could represent a new therapeutic target." @default.
• W2591994964 created "2017-03-16" @default.
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• W2591994964 date "2017-03-31" @default.
• W2591994964 modified "2023-10-16" @default.
• W2591994964 title "Deficiency in IRAK4 activity attenuates manifestations of murine Lupus" @default.
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• W2591994964 doi "https://doi.org/10.1002/eji.201646641" @default.
• W2591994964 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5575829" @default.
• W2591994964 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28295231" @default.
• W2591994964 hasPublicationYear "2017" @default.
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