The CD46 and Jagged1 interaction is critical for human T helper 1 immunity

CD46 is a complement regulator with important immune-related roles. CD46 functions as a pathogen receptor and is a potent co-stimulator for the induction of interferon-γ (IFN-γ)-secreting T helper 1 (T(H)1) effector T cells and their subsequent switch into interleukin-10 (IL-10)-producing regulatory...

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Detalles Bibliográficos
Autores principales: Le Friec, Gaëlle, Sheppard, Devon, Whiteman, Pat, Karsten, Christian M., Shamoun, Salley Al-Tilib, Laing, Adam, Bugeon, Laurence, Dallman, Margaret J., Melchionna, Teresa, Chillakuri, Chandramouli, Smith, Richard A., Drouet, Christian, Couzi, Lionel, Fremeaux-Bacchi, Veronique, Köhl, Jörg, Waddington, Simon N., McDonnell, James M., Baker, Alastair, Handford, Penny A., Lea, Susan M., Kemper, Claudia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2012
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3505834/
https://www.ncbi.nlm.nih.gov/pubmed/23086448
http://dx.doi.org/10.1038/ni.2454
Descripción
Sumario:CD46 is a complement regulator with important immune-related roles. CD46 functions as a pathogen receptor and is a potent co-stimulator for the induction of interferon-γ (IFN-γ)-secreting T helper 1 (T(H)1) effector T cells and their subsequent switch into interleukin-10 (IL-10)-producing regulatory T cells. Here, we identify the Notch protein family member Jagged1 as a new physiological ligand for CD46. Further, CD46 regulates Notch receptors and ligands expression during T cell activation and disturbance of the CD46-Notch crosstalk impedes IFN-γ induction and IL-10 switching. Importantly, CD4(+) T cells from CD46-deficient patients and patients with hypomorphic Jagged1 mutations (Alagille Syndrome) fail to mount appropriate T(H)1 responses in vitro and in vivo suggesting that CD46-Jagged1 crosstalk is responsible for the recurrent infections in subpopulations of these patients.

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