The CD46-Jagged1 interaction is critical for human TH1 immunity.
Nat Immunol
; 13(12): 1213-21, 2012 Dec.
Article
em En
| MEDLINE
| ID: mdl-23086448
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Ligação ao Cálcio
/
Ativação Linfocitária
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Células Th1
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Peptídeos e Proteínas de Sinalização Intercelular
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Proteína Cofatora de Membrana
/
Proteínas de Membrana
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Animals
/
Child
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Child, preschool
/
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article