@article{Le:2012:10.1038/ni.2454,
author = {Le, Friec G and Sheppard, D and Whiteman, P and Karsten, CM and Shamoun, SA-T and Laing, A and Bugeon, L and Dallman, MJ and Melchionna, T and Chillakuri, C and Smith, RA and Drouet, C and Couzi, L and Fremeaux-Bacchi, V and Koehl, J and Waddington, SN and McDonnell, JM and Baker, A and Handford, PA and Lea, SM and Kemper, C},
doi = {10.1038/ni.2454},
journal = {Nature Immunology},
pages = {1213--1221},
title = {The CD46-Jagged1 interaction is critical for human T(H)1 immunity},
url = {http://dx.doi.org/10.1038/ni.2454},
volume = {13},
year = {2012}
}

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TY  - JOUR
AB  - 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 TH1 responses in vitro and in vivo, which suggested that CD46-Jagged1 crosstalk is responsible for the recurrent infections in subpopulations of these patients.
AU  - Le,Friec G
AU  - Sheppard,D
AU  - Whiteman,P
AU  - Karsten,CM
AU  - Shamoun,SA-T
AU  - Laing,A
AU  - Bugeon,L
AU  - Dallman,MJ
AU  - Melchionna,T
AU  - Chillakuri,C
AU  - Smith,RA
AU  - Drouet,C
AU  - Couzi,L
AU  - Fremeaux-Bacchi,V
AU  - Koehl,J
AU  - Waddington,SN
AU  - McDonnell,JM
AU  - Baker,A
AU  - Handford,PA
AU  - Lea,SM
AU  - Kemper,C
DO  - 10.1038/ni.2454
EP  - 1221
PY  - 2012///
SN  - 1529-2908
SP  - 1213
TI  - The CD46-Jagged1 interaction is critical for human T(H)1 immunity
T2  - Nature Immunology
UR  - http://dx.doi.org/10.1038/ni.2454
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000311217900015&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/70242
VL  - 13
ER  - 

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