Notch signaling represents an important checkpoint between follicular T-helper and canonical T-helper 2 cell fate

Type-2 immunity is regulated by two distinct CD4+ T-cell subsets. T follicular helper (Tfh) cells are required for humoral hallmarks of type-2 inflammation. T-helper type-2 (Th2) cells orchestrate type-2 inflammation in peripheral tissues, such as the lung and intestine. Given the importance of Notc...

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Bibliographic Details
Published in:Mucosal immunology 2018-07, Vol.11 (4), p.1079-1091
Main Authors: Dell'Aringa, Mark, Reinhardt, R Lee
Format: Article
Language:English
Subjects:
Animals
CD4 antigen
Cell Differentiation
Cell fate
Cell Lineage
Cells, Cultured
Dendritic cells
Dendritic Cells - physiology
Germinal Center - immunology
Helper cells
Interleukin-4 - metabolism
Intestine
Ligands
Lymphocytes B
Lymphocytes T
Mice
Mice, Inbred C57BL
Mice, Knockout
Nippostrongylus - immunology
Receptor, Notch2 - genetics
Receptor, Notch2 - metabolism
Signal Transduction
Strongylida Infections - immunology
T cell receptors
T-Lymphocyte Subsets - physiology
Th2 Cells - physiology
Ubiquitin-Protein Ligases - genetics
Ubiquitin-Protein Ligases - metabolism
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Summary:Type-2 immunity is regulated by two distinct CD4+ T-cell subsets. T follicular helper (Tfh) cells are required for humoral hallmarks of type-2 inflammation. T-helper type-2 (Th2) cells orchestrate type-2 inflammation in peripheral tissues, such as the lung and intestine. Given the importance of Notch signaling in the establishment of other CD4+ T-helper cell subsets, we investigated whether canonical Notch activation could differentially impact Tfh and Th2 cell fate during the induction of type-2 immunity. These studies show that Tfh cell, but not Th2 cell, generation and function is reliant on Notch signaling. While early Tfh cell specification is influenced by functional Notch ligands on classical dendritic cells, functional Notch ligands on cells other than dendritic cells, T cells, B cells, and follicular dendritic cells are sufficient to achieve full Tfh cell commitment. These findings identify Notch signaling as an early lineage-determining factor between Tfh and Th2 cell fate.
ISSN:1933-0219
1935-3456
DOI:10.1038/s41385-018-0012-9