The CD46-Jagged1 interaction is critical for human TH1 immunity TL - 13

Gaëlle Friec, Devon Sheppard, Pat Whiteman, Christian M Karsten, Salley Shamoun, Adam Laing, Laurence Bugeon, Margaret J Dallman, Teresa Melchionna, Chandramouli Chillakuri, Richard A Smith, Christian Drouet, Lionel Couzi, Veronique Fremeaux-Bacchi, Jörg Köhl, Simon N Waddington, James M McDonnell, Alastair Baker, Penny A Handford, Susan M LeaClaudia Kemper


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 TH1 responses in vitro and in vivo, which suggested that CD46-Jagged1 crosstalk is responsible for the recurrent infections in subpopulations of these patients.
ZeitschriftNature Immunology
Jahrgang13 VN - r
Seiten (von - bis)1213-1221
PublikationsstatusVeröffentlicht - 2012


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