Genetic variation in UNC93B1, a key component in TLR trafficking, can lead to autoinflammation caused by increased TLR activity. Analysis of seven patient variants combined with a comprehensive alanine screen revealed that different regions of UNC93B1 selectively regulate different TLRs (Rael et al. https://doi.org/10.1084/jem.20232005; David et al. https://doi.org/10.1084/jem.20232066).
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http://dx.doi.org/10.1084/jem.20240841 | DOI Listing |
Lancet Infect Dis
December 2024
Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Electronic address:
Background: Plasmodium falciparum parasitaemia during pregnancy causes maternal, fetal, and infant mortality. Poor pregnancy outcomes are related to blood-stage parasite sequestration and the ensuing inflammatory response in the placenta, which decreases over successive pregnancies. A radiation-attenuated, non-replicating, whole-organism vaccine based on P falciparum sporozoites (PfSPZ Vaccine) has shown efficacy at preventing infection in African adults.
View Article and Find Full Text PDFJ Exp Med
August 2024
Department of Pediatrics and Center for Genetic Errors of Immunity, Columbia University Medical Center, New York, NY, USA.
Genetic variation in UNC93B1, a key component in TLR trafficking, can lead to autoinflammation caused by increased TLR activity. Analysis of seven patient variants combined with a comprehensive alanine screen revealed that different regions of UNC93B1 selectively regulate different TLRs (Rael et al. https://doi.
View Article and Find Full Text PDFCRISPR J
December 2023
RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
CRISPR-based genome-editing technologies, including nuclease editing, base editing, and prime editing, have recently revolutionized the development of therapeutics targeting disease-causing mutations. To advance the assessment and development of genome editing tools, a robust mouse model is valuable, particularly for evaluating activity and delivery strategies. In this study, we successfully generated a knock-in mouse line carrying the Traffic Light Reporter design known as TLR-multi-Cas variant 1 (TLR-MCV1).
View Article and Find Full Text PDFRespir Res
September 2023
Air Pollution Exposure Laboratory, Division of Respiratory Medicine, Department Medicine, Vancouver Coastal Health Research Institute, The University of British Columbia, Vancouver, BC, Canada.
Background: Environmental co-exposure to allergen and traffic-related air pollution is common globally and contributes to the exacerbation of respiratory diseases. Individual responses to environmental insults remain variable due to gene-environment interactions.
Objective: This study examined whether single nucleotide polymorphisms (SNPs) in lung cell surface receptor genes modifies lung function change and immune cell recruitment in allergen-sensitized individuals exposed to diesel exhaust (DE) and allergen.
Traffic
November 2023
Department of Biochemistry, University of Cambridge, Cambridge, UK.
Toll-Like Receptors (TLRs) play a pivotal role in immunity by recognising conserved structural features of pathogens and initiating the innate immune response. TLR signalling is subject to complex regulation that remains poorly understood. Here we show that two small type I transmembrane receptors, TMED2 and 7, that function as cargo sorting adaptors in the early secretory pathway are required for transport of TLRs from the ER to Golgi.
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