| http://purl.uniprot.org/citations/32487715 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/32487715 | http://www.w3.org/2000/01/rdf-schema#comment | "The dysregulation of multiple signaling pathways, including those through endosomal Toll-like receptors (TLRs), Fc gamma receptors (FcγR), and antigen receptors in B cells (BCR), promote an autoinflammatory loop in systemic lupus erythematosus (SLE). Here, we used selective small-molecule inhibitors to assess the regulatory roles of interleukin-1 receptor (IL-1R)-associated kinase 4 (IRAK4) and Bruton's tyrosine kinase (BTK) in these pathways. The inhibition of IRAK4 repressed SLE immune complex- and TLR7-mediated activation of human plasmacytoid dendritic cells (pDCs). Correspondingly, the expression of interferon (IFN)-responsive genes (IRGs) in cells and in mice was positively regulated by the kinase activity of IRAK4. Both IRAK4 and BTK inhibition reduced the TLR7-mediated differentiation of human memory B cells into plasmablasts. TLR7-dependent inflammatory responses were differentially regulated by IRAK4 and BTK by cell type: In pDCs, IRAK4 positively regulated NF-κB and MAPK signaling, whereas in B cells, NF-κB and MAPK pathways were regulated by both BTK and IRAK4. In the pristane-induced lupus mouse model, inhibition of IRAK4 reduced the expression of IRGs during disease onset. Mice engineered to express kinase-deficient IRAK4 were protected from both chemical (pristane-induced) and genetic (NZB/W_F1 hybrid) models of lupus development. Our findings suggest that kinase inhibitors of IRAK4 might be a therapeutic in patients with SLE."xsd:string |
| http://purl.uniprot.org/citations/32487715 | http://purl.org/dc/terms/identifier | "doi:10.1126/scisignal.aaz1053"xsd:string |
| http://purl.uniprot.org/citations/32487715 | http://purl.uniprot.org/core/author | "Huang Z."xsd:string |
| http://purl.uniprot.org/citations/32487715 | http://purl.uniprot.org/core/author | "Sun Y."xsd:string |
| http://purl.uniprot.org/citations/32487715 | http://purl.uniprot.org/core/author | "Xu D."xsd:string |
| http://purl.uniprot.org/citations/32487715 | http://purl.uniprot.org/core/author | "Brightbill H.D."xsd:string |
| http://purl.uniprot.org/citations/32487715 | http://purl.uniprot.org/core/author | "Roose-Girma M."xsd:string |
| http://purl.uniprot.org/citations/32487715 | http://purl.uniprot.org/core/author | "Wong A."xsd:string |
| http://purl.uniprot.org/citations/32487715 | http://purl.uniprot.org/core/author | "Kiefer J.R."xsd:string |
| http://purl.uniprot.org/citations/32487715 | http://purl.uniprot.org/core/author | "Bao K."xsd:string |
| http://purl.uniprot.org/citations/32487715 | http://purl.uniprot.org/core/author | "Ghilardi N."xsd:string |
| http://purl.uniprot.org/citations/32487715 | http://purl.uniprot.org/core/author | "Francis R."xsd:string |
| http://purl.uniprot.org/citations/32487715 | http://purl.uniprot.org/core/author | "Lee W.P."xsd:string |
| http://purl.uniprot.org/citations/32487715 | http://purl.uniprot.org/core/author | "Vucic D."xsd:string |
| http://purl.uniprot.org/citations/32487715 | http://purl.uniprot.org/core/author | "Tam L."xsd:string |
| http://purl.uniprot.org/citations/32487715 | http://purl.uniprot.org/core/author | "Varfolomeev E."xsd:string |
| http://purl.uniprot.org/citations/32487715 | http://purl.uniprot.org/core/author | "Pappu R."xsd:string |
| http://purl.uniprot.org/citations/32487715 | http://purl.uniprot.org/core/author | "Warming S."xsd:string |
| http://purl.uniprot.org/citations/32487715 | http://purl.uniprot.org/core/author | "McKenzie B.S."xsd:string |
| http://purl.uniprot.org/citations/32487715 | http://purl.uniprot.org/core/author | "Suto E."xsd:string |
| http://purl.uniprot.org/citations/32487715 | http://purl.uniprot.org/core/author | "Pang J."xsd:string |
| http://purl.uniprot.org/citations/32487715 | http://purl.uniprot.org/core/author | "Eastham-Anderson J."xsd:string |
| http://purl.uniprot.org/citations/32487715 | http://purl.uniprot.org/core/author | "Asghari V."xsd:string |
| http://purl.uniprot.org/citations/32487715 | http://purl.uniprot.org/core/author | "Paler-Martinez A."xsd:string |