Glycogen synthase kinase-3 promotes T helper type 17 differentiation by promoting interleukin-9 production.
Animals
Cell Differentiation
Cells, Cultured
Core Binding Factor alpha Subunits
/ genetics
Glycogen Synthase Kinase 3
/ genetics
Interleukin-17
/ genetics
Interleukin-9
/ metabolism
Lymphocyte Activation
Lymphocyte Depletion
Mice
Mice, Inbred C57BL
Mice, Knockout
Promoter Regions, Genetic
/ genetics
STAT3 Transcription Factor
/ genetics
Th17 Cells
/ immunology
T helper type 17 cells
glycogen synthase kinase-3
interleukin-9
Journal
Immunology
ISSN: 1365-2567
Titre abrégé: Immunology
Pays: England
ID NLM: 0374672
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
10
12
2019
revised:
12
03
2020
accepted:
31
03
2020
pubmed:
12
4
2020
medline:
27
5
2021
entrez:
12
4
2020
Statut:
ppublish
Résumé
T helper type 17 (Th17) cells are recognized as important contributors to the deleterious effects of several neurological and psychiatric diseases. Clarifying mechanisms that control the production of Th17 cells may therefore provide new strategies for developing novel interventions in a broad spectrum of disorders. Th17 cell differentiation is promoted by glycogen synthase kinase-3 (GSK3), but the mechanisms for this are only beginning to be understood. Using T-cell-selective depletion of GSK3β and multiple selective pharmacological GSK3 inhibitors, we found that GSK3 inhibition decreased C-C motif chemokine (ccl)20, C-C motif chemokine receptor (ccr)6, interleukin (IL)-9, Runt-related transcription factor (Runx)1, interferon regulatory factor (Irf)4 and c-maf mRNA expression after 2 days of Th17 cell differentiation in vitro. These effects were found to be independent of the master regulator transcription factor retinoic acid receptor-related orphan receptor γT (RORγT), as GSK3 inhibition still reduced Th17 cell differentiation in RORγT-depleted cells. Because IL-9 was approximately ninefold down-regulated in GSK3β
Identifiants
pubmed: 32277469
doi: 10.1111/imm.13199
pmc: PMC7370138
doi:
Substances chimiques
Core Binding Factor alpha Subunits
0
Interleukin-17
0
Interleukin-9
0
STAT3 Transcription Factor
0
Glycogen Synthase Kinase 3
EC 2.7.11.26
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
357-365Subventions
Organisme : NIMH NIH HHS
ID : R01 MH104656
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH110415
Pays : United States
Informations de copyright
© 2020 John Wiley & Sons Ltd.
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