21 research outputs found
Divergent phenotypes in siblings with identical novel mutations in the HNF-1α gene leading to maturity onset diabetes of the young type 3
Joint effects of diabetic-related genomic loci on the therapeutic efficacy of oral anti-diabetic drugs in Chinese type 2 diabetes patients
Scaling approach in predicting the seatbelt loading and kinematics of vulnerable occupants: How far can we go?
Screening of HNF1A and HNF4A mutation and clinical phenotype analysis in a large cohort of Chinese patients with maturity-onset diabetes of the young
Identification of MODY among patients screened for gestational diabetes: a clinician’s guide
The receptor TREML4 amplifies TLR7-mediated signaling during antiviral responses and autoimmunity
The genes and pathways that fine-tune TLR7-mediated innate inflammatory responses remain to be fully elucidated. Using an unbiased genome-scale shRNA screen, 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 interferon due to impaired phosphorylation of the transcription factor STAT1 by the MAP kinase p38 and decreased recruitment of MyD88 to TLR7. TREML4 deficiency reduced production of inflammatory cytokines and autoantibodies in SLE-prone MRL/lpr mice and inhibited the antiviral immune response to influenza. 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. In humans and mice combined the Toll-like receptor (TLR) family consists of thirteen members that can be divided into two subgroups based on their cellular location1. Cell surface TLRs (TLR1, TLR2, TLR4, TLR5 and TLR6) recognize various molecules in bacteria and fungi. Intracellular TLRs (TLR3, TLR7, TLR9, TLR13) recognize nuclei