| First Author | Le Friec G | Year | 2012 |
| Journal | Nat Immunol | Volume | 13 |
| Issue | 12 | Pages | 1213-21 |
| PubMed ID | 23086448 | Mgi Jnum | J:190684 |
| Mgi Id | MGI:5449468 | Doi | 10.1038/ni.2454 |
| Citation | Le Friec G, et al. (2012) The CD46-Jagged1 interaction is critical for human TH1 immunity. Nat Immunol 13(12):1213-21 |
| abstractText | 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-gamma (IFN-gamma)-secreting effector T helper type 1 (T(H)1) 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-gamma 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. |
