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Nat Immunol. 2015 Apr 6. doi: 10.1038/ni.3143. [Epub ahead of print]
The receptor TREML4 amplifies TLR7-mediated signaling during antiviral responses and autoimmunity.
Ramirez-Ortiz ZG1, Prasad A1, Griffith JW1, Pendergraft WF 3rd2, Cowley GS3, Root DE3, Tai M1, Luster AD1, El Khoury J4, Hacohen N5, Means TK1.
Author information
Abstract
The molecules and pathways that fine-tune innate inflammatory responses mediated by Toll-like receptor 7 (TLR7) remain to be fully elucidated. Using an unbiased genome-scale screen with short hairpin RNA (shRNA), we identified the receptor TREML4 as an essential positive regulator of TLR7 signaling. Macrophages from Treml4-/- mice were hyporesponsive to TLR7 agonists and failed to produce type I interferons due to impaired phosphorylation of the transcription factor STAT1 by the mitogen-activated protein kinase p38 and decreased recruitment of the adaptor MyD88 to TLR7. TREML4 deficiency reduced the production of inflammatory cytokines and autoantibodies in MRL/lpr mice, which are prone to systemic lupus erythematosus (SLE), and inhibited the antiviral immune response to influenza virus. Our data identify TREML4 as a positive regulator of TLR7 signaling and provide insight into the molecular mechanisms that control antiviral immunity and the development of autoimmunity.
PMID: 25848864 [PubMed - as supplied by publisher]
The receptor TREML4 amplifies TLR7-mediated signaling during antiviral responses and autoimmunity.
Ramirez-Ortiz ZG1, Prasad A1, Griffith JW1, Pendergraft WF 3rd2, Cowley GS3, Root DE3, Tai M1, Luster AD1, El Khoury J4, Hacohen N5, Means TK1.
Author information
Abstract
The molecules and pathways that fine-tune innate inflammatory responses mediated by Toll-like receptor 7 (TLR7) remain to be fully elucidated. Using an unbiased genome-scale screen with short hairpin RNA (shRNA), we identified the receptor TREML4 as an essential positive regulator of TLR7 signaling. Macrophages from Treml4-/- mice were hyporesponsive to TLR7 agonists and failed to produce type I interferons due to impaired phosphorylation of the transcription factor STAT1 by the mitogen-activated protein kinase p38 and decreased recruitment of the adaptor MyD88 to TLR7. TREML4 deficiency reduced the production of inflammatory cytokines and autoantibodies in MRL/lpr mice, which are prone to systemic lupus erythematosus (SLE), and inhibited the antiviral immune response to influenza virus. Our data identify TREML4 as a positive regulator of TLR7 signaling and provide insight into the molecular mechanisms that control antiviral immunity and the development of autoimmunity.
PMID: 25848864 [PubMed - as supplied by publisher]