The CD46-Jagged1 interaction is critical for human TH1 immunity TL  - 13

Gaëlle Friec; Devon Sheppard; Pat Whiteman; Christian M Karsten; Salley Shamoun; Adam Laing; Laurence Bugeon; Margaret J Dallman; Teresa Melchionna; Chandramouli Chillakuri; Richard A Smith; Christian Drouet; Lionel Couzi; Veronique Fremeaux-Bacchi; Jörg Köhl; Simon N Waddington; James M McDonnell; Alastair Baker; Penny A Handford; Susan M Lea; Claudia Kemper

doi:10.1038/ni.2454

The CD46-Jagged1 interaction is critical for human TH1 immunity TL - 13

Gaëlle Friec, Devon Sheppard, Pat Whiteman, Christian M Karsten, Salley Shamoun, Adam Laing, Laurence Bugeon, Margaret J Dallman, Teresa Melchionna, Chandramouli Chillakuri, Richard A Smith, Christian Drouet, Lionel Couzi, Veronique Fremeaux-Bacchi, Jörg Köhl, Simon N Waddington, James M McDonnell, Alastair Baker, Penny A Handford, Susan M LeaClaudia Kemper

Institute of Systemic Inflamation Research

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 (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.

Original language	English
Journal	Nature Immunology
Volume	13 VN - r
Issue number	12
Pages (from-to)	1213-1221
Number of pages	9
ISSN	1529-2908
DOIs	https://doi.org/10.1038/ni.2454
Publication status	Published - 2012

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Friec, G., Sheppard, D., Whiteman, P., Karsten, C. M., Shamoun, S., Laing, A., Bugeon, L., Dallman, M. J., Melchionna, T., Chillakuri, C., Smith, R. A., Drouet, C., Couzi, L., Fremeaux-Bacchi, V., Köhl, J., Waddington, S. N., McDonnell, J. M., Baker, A., Handford, P. A., ... Kemper, C. (2012). The CD46-Jagged1 interaction is critical for human TH1 immunity TL - 13. Nature Immunology, 13 VN - r(12), 1213-1221. https://doi.org/10.1038/ni.2454

@article{686670726f35462181a9c93ff699aab7,

title = "The CD46-Jagged1 interaction is critical for human TH1 immunity TL - 13",

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 (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.",

author = "Ga{\"e}lle Friec and Devon Sheppard and Pat Whiteman and Karsten, {Christian M} and Salley Shamoun and Adam Laing and Laurence Bugeon and Dallman, {Margaret J} and Teresa Melchionna and Chandramouli Chillakuri and Smith, {Richard A} and Christian Drouet and Lionel Couzi and Veronique Fremeaux-Bacchi and J{\"o}rg K{\"o}hl and Waddington, {Simon N} and McDonnell, {James M} and Alastair Baker and Handford, {Penny A} and Lea, {Susan M} and Claudia Kemper",

year = "2012",

doi = "10.1038/ni.2454",

language = "English",

volume = "13 VN - r",

pages = "1213--1221",

journal = "Nature Immunology",

issn = "1529-2908",

number = "12",

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Friec, G, Sheppard, D, Whiteman, P, Karsten, CM, Shamoun, S, Laing, A, Bugeon, L, Dallman, MJ, Melchionna, T, Chillakuri, C, Smith, RA, Drouet, C, Couzi, L, Fremeaux-Bacchi, V, Köhl, J, Waddington, SN, McDonnell, JM, Baker, A, Handford, PA, Lea, SM & Kemper, C 2012, 'The CD46-Jagged1 interaction is critical for human TH1 immunity TL - 13', Nature Immunology, vol. 13 VN - r, no. 12, pp. 1213-1221. https://doi.org/10.1038/ni.2454

TY - JOUR

T1 - The CD46-Jagged1 interaction is critical for human TH1 immunity TL - 13

AU - Friec, Gaëlle

AU - Sheppard, Devon

AU - Whiteman, Pat

AU - Karsten, Christian M

AU - Shamoun, Salley

AU - Laing, Adam

AU - Bugeon, Laurence

AU - Dallman, Margaret J

AU - Melchionna, Teresa

AU - Chillakuri, Chandramouli

AU - Smith, Richard A

AU - Drouet, Christian

AU - Couzi, Lionel

AU - Fremeaux-Bacchi, Veronique

AU - Köhl, Jörg

AU - Waddington, Simon N

AU - McDonnell, James M

AU - Baker, Alastair

AU - Handford, Penny A

AU - Lea, Susan M

AU - Kemper, Claudia

PY - 2012

Y1 - 2012

N2 - 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.

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.

U2 - 10.1038/ni.2454

DO - 10.1038/ni.2454

M3 - Journal articles

SN - 1529-2908

VL - 13 VN - r

SP - 1213

EP - 1221

JO - Nature Immunology

JF - Nature Immunology

IS - 12

ER -

The CD46-Jagged1 interaction is critical for human TH1 immunity TL - 13

Abstract

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