Glutamine promotes the generation of B10
B10
GSK3
IL-10
glutamine
immunotherapy
mTOR
metabolism
regulatory B cells
Journal
European journal of immunology
ISSN: 1521-4141
Titre abrégé: Eur J Immunol
Pays: Germany
ID NLM: 1273201
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
revised:
23
11
2021
received:
20
05
2021
accepted:
20
12
2021
pubmed:
29
12
2021
medline:
6
5
2022
entrez:
28
12
2021
Statut:
ppublish
Résumé
Alterations in cell metabolism can shift the differentiation of immune cells toward a regulatory or inflammatory phenotype, thus, opening up new therapeutic opportunities for immune-related diseases. Indeed, growing knowledge on T- cell metabolism has revealed differences in the metabolic programs of suppressive Tregs as compared to inflammatory Th1 and Th17 cells. In addition to Tregs, IL-10-producing regulatory B cells are crucial for maintaining tolerance, inhibiting inflammation, and autoimmunity. Yet, the metabolic networks regulating diverse B-lymphocyte responses are not well known. Here, we show that glutaminase blockade decreased downstream mTOR activation and attenuated IL-10 secretion. Direct suppression of mTOR activity by rapamycin selectively impaired IL-10 production by B cells whereas secretion was restored upon Glycogen synthase kinase 3 (GSK3) inhibition. Mechanistically, we found mTORC1 activation leads to GSK3 inhibition, identifying a key signalling pathway regulating IL-10 secretion by B lymphocytes. Thus, our results identify glutaminolysis and the mTOR/GSK3 signalling axis, as critical regulators of the generation of IL-10 producing B cells with regulatory functions.
Identifiants
pubmed: 34961940
doi: 10.1002/eji.202149387
doi:
Substances chimiques
Glutamine
0RH81L854J
Interleukin-10
130068-27-8
TOR Serine-Threonine Kinases
EC 2.7.11.1
Glycogen Synthase Kinase 3
EC 2.7.11.26
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
418-430Informations de copyright
© 2022 Wiley-VCH GmbH.
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