Glutamine promotes the generation of B10 + cells via the mTOR/GSK3 pathway.

Autor:	Mielle J; Institut de Génétique Moléculaire de Montpellier, University of Montpellier, Montpellier, France.; Department of Rheumatology, CHU de Montpellier, Montpellier, France., Morel J; Institut de Génétique Moléculaire de Montpellier, University of Montpellier, Montpellier, France.; Department of Rheumatology, CHU de Montpellier, Montpellier, France.; PhyMedExp, University of Montpellier, Montpellier, France., Elhmioui J; Institut de Génétique Moléculaire de Montpellier, University of Montpellier, Montpellier, France., Combe B; Institut de Génétique Moléculaire de Montpellier, University of Montpellier, Montpellier, France.; Department of Rheumatology, CHU de Montpellier, Montpellier, France.; PhyMedExp, University of Montpellier, Montpellier, France., Macia L; Charles Perkins Centre, University of Sydney, Sydney, Australia.; School of Medical Sciences, Faculty of Medicine and Health, Sydney, Australia., Dardalhon V; Institut de Génétique Moléculaire de Montpellier, University of Montpellier, Montpellier, France., Taylor N; Institut de Génétique Moléculaire de Montpellier, University of Montpellier, Montpellier, France., Audo R; Institut de Génétique Moléculaire de Montpellier, University of Montpellier, Montpellier, France.; Department of Rheumatology, CHU de Montpellier, Montpellier, France.; PhyMedExp, University of Montpellier, Montpellier, France., Daien C; Institut de Génétique Moléculaire de Montpellier, University of Montpellier, Montpellier, France.; Department of Rheumatology, CHU de Montpellier, Montpellier, France.; PhyMedExp, University of Montpellier, Montpellier, France.
Jazyk:	angličtina
Zdroj:	European journal of immunology [Eur J Immunol] 2022 Mar; Vol. 52 (3), pp. 418-430. Date of Electronic Publication: 2022 Feb 01.
DOI:	10.1002/eji.202149387
Abstrakt:	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. (© 2022 Wiley-VCH GmbH.)
Databáze:	MEDLINE
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