Notch regulates Th17 differentiation and controls trafficking of IL-17 and metabolic regulators within Th17 cells in a context-dependent manner.

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State: Public
Version: Final published version
Serval ID
serval:BIB_6327A7D47779
Type
Article: article from journal or magazin.
Collection
Publications
Title
Notch regulates Th17 differentiation and controls trafficking of IL-17 and metabolic regulators within Th17 cells in a context-dependent manner.
Journal
Scientific reports
Author(s)
Coutaz M., Hurrell B.P., Auderset F., Wang H., Siegert S., Eberl G., Ho P.C., Radtke F., Tacchini-Cottier F.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Publication state
Published
Issued date
15/12/2016
Peer-reviewed
Oui
Volume
6
Pages
39117
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
Th17 cells play critical roles in host defense and autoimmunity. Emerging data support a role for Notch signaling in Th17 cell differentiation but whether it is a positive or negative regulator remains unclear. We report here that T cell-specific deletion of Notch receptors enhances Th17 cell differentiation in the gut, with a corresponding increase in IL-17 secretion. An increase in Th17 cell frequency was similarly observed following immunization of T cell specific Notch mutant mice with OVA/CFA. However, in this setting, Th17 cytokine secretion was impaired, and increased intracellular retention of IL-17 was observed. Intracellular IL-17 co-localized with the CD71 iron transporter in the draining lymph node of both control and Notch-deficient Th17 cells. Immunization induced CD71 surface expression in control, but not in Notch-deficient Th17 cells, revealing defective CD71 intracellular transport in absence of Notch signaling. Moreover, Notch receptor deficient Th17 cells had impaired mTORC2 activity. These data reveal a context-dependent impact of Notch on vesicular transport during high metabolic demand suggesting a role for Notch signaling in the bridging of T cell metabolic demands and effector functions. Collectively, our findings indicate a prominent regulatory role for Notch signaling in the fine-tuning of Th17 cell differentiation and effector function.
Keywords
Animals, Antigens, CD/metabolism, Cell Differentiation, Cells, Cultured, Immunization/methods, Interleukin-17/metabolism, Interleukin-17/secretion, Mice, Protein Transport, Receptors, Notch/metabolism, Receptors, Transferrin/metabolism, Signal Transduction, Th17 Cells/cytology
Pubmed
Web of science
Open Access
Yes
Create date
29/12/2016 15:05
Last modification date
20/08/2019 15:19
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