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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 (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-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.

Original publication




Journal article


Nat Immunol

Publication Date





1213 - 1221


Adult, Alagille Syndrome, Animals, Calcium-Binding Proteins, Cells, Cultured, Child, Child, Preschool, Humans, Intercellular Signaling Peptides and Proteins, Interferon-gamma, Interleukin-10, Jagged-1 Protein, Lymphocyte Activation, Membrane Cofactor Protein, Membrane Proteins, Mice, Mice, SCID, Mice, Transgenic, RNA Interference, RNA, Small Interfering, Serrate-Jagged Proteins, Th1 Cells, alpha Catenin