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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
The CD46-Jagged1 interaction is critical for human T H 1 immunity
Nature Immunology, Volume 13, No. 12, Year 2012
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Description
CD46 is a complement regulator with important roles related to the immune response. CD46 functions as a pathogen receptor and is a potent costimulator for the induction of interferon-γ (IFN-γ)-secreting effector T helper type 1 (TH1) cells and their subsequent switch into interleukin 10 (IL-10)-producing regulatory T cells. Here we identified the Notch family member Jagged1 as a physiological ligand for CD46. Furthermore, we found that CD46 regulated the expression of Notch receptors and ligands during T cell activation and that disturbance of the CD46-Notch crosstalk impeded induction of IFN-γ and switching to IL-10. Notably, CD4+ T cells from CD46-deficient patients and patients with hypomorphic mutations in the gene encoding Jagged1 (Alagille syndrome) failed to mount appropriate T H 1 responses in vitro and in vivo, which suggested that CD46-Jagged1 crosstalk is responsible for the recurrent infections in subpopulations of these patients. © 2012 Nature America, Inc. All rights reserved.
Authors & Co-Authors
Sheppard, Devon
United Kingdom, Oxford
University of Oxford
Smith, Richard Alan G.
United Kingdom, London
King's College London
Drouet, Christian
France, Paris
Cnrs Centre National de la Recherche Scientifique
Couzi, Lionel
France, Talence
Centre Hospitalier Universitaire de Bordeaux
Frémeaux-Bacchi, Véronique
France, Paris
Inserm
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
Waddington, Simon N.
United Kingdom, London
University College London
Baker, A. J.
United Kingdom, London
King's College London
Handford, Penny A.
United Kingdom, Oxford
University of Oxford Medical Sciences Division
Lea, Susan Mary
United Kingdom, Oxford
University of Oxford
Statistics
Citations: 132
Authors: 9
Affiliations: 11
Identifiers
Doi:
10.1038/ni.2454
ISSN:
15292916
Research Areas
Genetics And Genomics