Regulation of innate and adaptive immunity by Notch View Full Text


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Article Info

DATE

2013-05-13

AUTHORS

Freddy Radtke, H. Robson MacDonald, Fabienne Tacchini-Cottier

ABSTRACT

Key PointsNotch signalling has several important roles in driving both the development and function of cells of the immune system.During lymphocyte development, different Notch ligand and receptor pairs promote commitment to specific cell lineages. Delta-like ligand 4 (DLL4) interacts with Notch 1 to specify thymic T cell commitment, whereas DLL1–Notch 2 signalling promotes lineage commitment in splenic marginal zone B cells. The development of certain subsets of dendritic cells in the spleen and in the lamina propria of the intestine is also dependent on canonical Notch 2 signalling.Notch signalling influences the development and expansion of certain populations of innate lymphoid cells (ILCs), which are a recently described class of innate-like immune cells.Notch signalling is involved in T helper (TH) cell differentiation and function. DLL-mediated Notch signalling favours the development and effector functions of interferon-γ-secreting TH1 cells, whereas Jagged ligands induce the development of TH2 and regulatory T cells.Genetic, pharmacological or antibody-mediated blockade of Notch signalling can reduce the clinical severity of several mouse models of autoimmune disease.Blockade of Notch signalling in allogeneic bone marrow transplantation models inhibits pathological graft-versus-host disease while preserving beneficial graft-versus-tumour effects.This suggest that modulation of Notch signalling could be used to target immune cells during pathological conditions. More... »

PAGES

427-437

References to SciGraph publications

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    http://scigraph.springernature.com/pub.10.1038/nri3445

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    42 schema:description Key PointsNotch signalling has several important roles in driving both the development and function of cells of the immune system.During lymphocyte development, different Notch ligand and receptor pairs promote commitment to specific cell lineages. Delta-like ligand 4 (DLL4) interacts with Notch 1 to specify thymic T cell commitment, whereas DLL1–Notch 2 signalling promotes lineage commitment in splenic marginal zone B cells. The development of certain subsets of dendritic cells in the spleen and in the lamina propria of the intestine is also dependent on canonical Notch 2 signalling.Notch signalling influences the development and expansion of certain populations of innate lymphoid cells (ILCs), which are a recently described class of innate-like immune cells.Notch signalling is involved in T helper (TH) cell differentiation and function. DLL-mediated Notch signalling favours the development and effector functions of interferon-γ-secreting TH1 cells, whereas Jagged ligands induce the development of TH2 and regulatory T cells.Genetic, pharmacological or antibody-mediated blockade of Notch signalling can reduce the clinical severity of several mouse models of autoimmune disease.Blockade of Notch signalling in allogeneic bone marrow transplantation models inhibits pathological graft-versus-host disease while preserving beneficial graft-versus-tumour effects.This suggest that modulation of Notch signalling could be used to target immune cells during pathological conditions.
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    48 schema:keywords B cells
    49 DLL
    50 Delta-like ligand 4
    51 Jagged ligands
    52 Notch
    53 Notch ligands
    54 Notch signaling
    55 Notch-1
    56 Notch-2
    57 T cell commitment
    58 T cells
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    60 Th1 cells
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    62 adaptive immunity
    63 allogeneic bone marrow transplantation model
    64 antibody-mediated blockade
    65 autoimmune diseases
    66 beneficial graft
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    68 blockade of Notch
    69 bone marrow transplantation model
    70 cell commitment
    71 cell differentiation
    72 cell lineages
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    74 certain populations
    75 certain subsets
    76 class
    77 clinical severity
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    79 conditions
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    81 development
    82 development of Th2
    83 different Notch ligands
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    85 disease
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    87 effector functions
    88 expansion
    89 function
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    91 graft
    92 helper cell differentiation
    93 host disease
    94 immune cells
    95 immune system
    96 immunity
    97 important role
    98 influence
    99 innate lymphoid cells
    100 innate-like immune cells
    101 interferon
    102 intestine
    103 lamina propria
    104 ligand 4
    105 ligands
    106 lineage commitment
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    108 lymphocyte development
    109 lymphoid cells
    110 marginal zone B cells
    111 model
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    113 mouse model
    114 pairs
    115 pathological conditions
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    117 propria
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    121 role
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