The CD46-Jagged1 interaction is critical for human T(H)1 immunity

Gaelle Le Friec; Devon Sheppard; Pat Whiteman; Christian M. Karsten; Salley Al-Tilib Shamoun; Adam Laing; Laurence Bugeon; Margaret J. Dallman; Teresa Melchionna; Chandramouli Chillakuri; Richard A. Smith; Christian Drouet; Lionel Couzi; Veronique Fremeaux-Bacchi; Joerg Koehl; 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 T(H)1 immunity

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

Research output: Contribution to journal › Article › peer-review

143 Citations (Scopus)

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

Access to Document

10.1038/ni.2454

Cite this

Le Friec, G., Sheppard, D., Whiteman, P., Karsten, C. M., Shamoun, S. A.-T., Laing, A., Bugeon, L., Dallman, M. J., Melchionna, T., Chillakuri, C., Smith, R. A., Drouet, C., Couzi, L., Fremeaux-Bacchi, V., Koehl, J., Waddington, S. N., McDonnell, J. M., Baker, A., Handford, P. A., ... Kemper, C. (2012). The CD46-Jagged1 interaction is critical for human T(H)1 immunity. Nature Immunology, 13(12), 1213-1221. https://doi.org/10.1038/ni.2454

@article{9a80c7142bbc4b6bbce857824dab207c,

title = "The CD46-Jagged1 interaction is critical for human T(H)1 immunity",

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-gamma (IFN-gamma)-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-gamma 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.",

author = "{Le Friec}, Gaelle and Devon Sheppard and Pat Whiteman and Karsten, {Christian M.} and Shamoun, {Salley Al-Tilib} 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 Joerg Koehl and Waddington, {Simon N.} and McDonnell, {James M.} and Alastair Baker and Handford, {Penny A.} and Lea, {Susan M.} and Claudia Kemper",

year = "2012",

month = dec,

doi = "10.1038/ni.2454",

language = "English",

volume = "13",

pages = "1213--1221",

journal = "Nature Immunology",

issn = "1529-2908",

publisher = "Nature Publishing Group",

number = "12",

}

Le Friec, G, Sheppard, D, Whiteman, P, Karsten, CM, Shamoun, SA-T, Laing, A, Bugeon, L, Dallman, MJ, Melchionna, T, Chillakuri, C, Smith, RA, Drouet, C, Couzi, L, Fremeaux-Bacchi, V, Koehl, J, Waddington, SN, McDonnell, JM, Baker, A, Handford, PA, Lea, SM & Kemper, C 2012, 'The CD46-Jagged1 interaction is critical for human T(H)1 immunity', Nature Immunology, vol. 13, no. 12, pp. 1213-1221. https://doi.org/10.1038/ni.2454

TY - JOUR

T1 - The CD46-Jagged1 interaction is critical for human T(H)1 immunity

AU - Le Friec, Gaelle

AU - Sheppard, Devon

AU - Whiteman, Pat

AU - Karsten, Christian M.

AU - Shamoun, Salley Al-Tilib

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 - Koehl, Joerg

AU - Waddington, Simon N.

AU - McDonnell, James M.

AU - Baker, Alastair

AU - Handford, Penny A.

AU - Lea, Susan M.

AU - Kemper, Claudia

PY - 2012/12

Y1 - 2012/12

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-gamma (IFN-gamma)-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-gamma 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.

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-gamma (IFN-gamma)-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-gamma 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.

U2 - 10.1038/ni.2454

DO - 10.1038/ni.2454

M3 - Article

SN - 1529-2908

VL - 13

SP - 1213

EP - 1221

JO - Nature Immunology

JF - Nature Immunology

IS - 12

ER -

The CD46-Jagged1 interaction is critical for human T(H)1 immunity

Abstract

Access to Document

Fingerprint

Cite this