The receptor TREML4 amplifies TLR7-mediated signaling during antiviral responses and autoimmunity.

Autor: Ramirez-Ortiz ZG; Center for Immunology and Inflammatory Diseases and Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA., Prasad A; Center for Immunology and Inflammatory Diseases and Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA., Griffith JW; Center for Immunology and Inflammatory Diseases and Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA., Pendergraft WF 3rd; University of North Carolina Kidney Center, Burnett Womack Building, Chapel Hill, North Carolina, USA., Cowley GS; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA., Root DE; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA., Tai M; Center for Immunology and Inflammatory Diseases and Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA., Luster AD; Center for Immunology and Inflammatory Diseases and Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA., El Khoury J; 1] Center for Immunology and Inflammatory Diseases and Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA. [2] Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA., Hacohen N; 1] Center for Immunology and Inflammatory Diseases and Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA. [2] Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA., Means TK; Center for Immunology and Inflammatory Diseases and Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2015 May; Vol. 16 (5), pp. 495-504. Date of Electronic Publication: 2015 Apr 06.
DOI: 10.1038/ni.3143
Abstrakt: 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.
Databáze: MEDLINE
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