In:
Science Advances, American Association for the Advancement of Science (AAAS), Vol. 5, No. 7 ( 2019-07-05)
Abstract:
Type I interferons are highly potent cytokines essential for self-protection against tumors and infections. Deregulations of type I interferon signaling are associated with multiple diseases that require novel therapeutic options. Here, we identified the small molecule, IT1t, a previously described CXCR4 ligand, as a highly potent inhibitor of Toll-like receptor 7 (TLR7)–mediated inflammation. IT1t inhibits chemical (R848) and natural (HIV) TLR7-mediated inflammation in purified human plasmacytoid dendritic cells from blood and human tonsils. In a TLR7-dependent lupus-like model, in vivo treatment of mice with IT1t drives drastic reduction of both systemic inflammation and anti–double-stranded DNA autoantibodies and prevents glomerulonephritis. Furthermore, IT1t controls inflammation, including interferon α secretion, in resting and stimulated cells from patients with systemic lupus erythematosus. Our findings highlight a groundbreaking immunoregulatory property of CXCR4 signaling that opens new therapeutic perspectives in inflammatory settings and autoimmune diseases.
Type of Medium:
Online Resource
ISSN:
2375-2548
DOI:
10.1126/sciadv.aav9019
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2019
detail.hit.zdb_id:
2810933-8
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