tetano
Editor, Senior Moderator
Nat Immunol. 2015 Apr 6. doi: 10.1038/ni.3143. [Epub ahead of print]
[h=1]The receptor TREML4 amplifies TLR7-mediated signaling during antiviral responses and autoimmunity.[/h] Ramirez-Ortiz ZG[SUP]1[/SUP], Prasad A[SUP]1[/SUP], Griffith JW[SUP]1[/SUP], Pendergraft WF 3rd[SUP]2[/SUP], Cowley GS[SUP]3[/SUP], Root DE[SUP]3[/SUP], Tai M[SUP]1[/SUP], Luster AD[SUP]1[/SUP], El Khoury J[SUP]4[/SUP], Hacohen N[SUP]5[/SUP], Means TK[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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[SUP]-/-[/SUP] 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]
[h=1]The receptor TREML4 amplifies TLR7-mediated signaling during antiviral responses and autoimmunity.[/h] Ramirez-Ortiz ZG[SUP]1[/SUP], Prasad A[SUP]1[/SUP], Griffith JW[SUP]1[/SUP], Pendergraft WF 3rd[SUP]2[/SUP], Cowley GS[SUP]3[/SUP], Root DE[SUP]3[/SUP], Tai M[SUP]1[/SUP], Luster AD[SUP]1[/SUP], El Khoury J[SUP]4[/SUP], Hacohen N[SUP]5[/SUP], Means TK[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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[SUP]-/-[/SUP] 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]