The CD46-Jagged1 interaction is critical for human T H 1 immunity

Journal article

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: Le Friec, G; Sheppard, D; Whiteman, P; Karsten, C; Shamoun, S

• Journal: Nature Immunology
• Volume: 13
• Issue: 12
• Pages: 1213-1221
• Publication date: 2012-12-01
• DOI: 10.1038/ni.2454
• EISSN: 1529-2916
• ISSN: 1529-2908
• Language: English