Antigen-specific downregulation of miR-150 in CD4 T cells promotes cell survival

MicroRNA-150 (miR-150) has been shown to play a general role in the immune system, but very little is known about its role on CD4+ T cell responses. During T cell responses against superantigen Staphylococcal Enterotoxin A, miR-150 expression was down-regulated in antigen-specific CD4+ T cells but u...

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Main Authors: Antoine Ménoret, Federica Agliano, Timofey A. Karginov, Keaton S. Karlinsey, Beiyan Zhou, Anthony T. Vella
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-01-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1102403/full
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author Antoine Ménoret
Federica Agliano
Timofey A. Karginov
Keaton S. Karlinsey
Beiyan Zhou
Anthony T. Vella
author_facet Antoine Ménoret
Federica Agliano
Timofey A. Karginov
Keaton S. Karlinsey
Beiyan Zhou
Anthony T. Vella
author_sort Antoine Ménoret
collection DOAJ
description MicroRNA-150 (miR-150) has been shown to play a general role in the immune system, but very little is known about its role on CD4+ T cell responses. During T cell responses against superantigen Staphylococcal Enterotoxin A, miR-150 expression was down-regulated in antigen-specific CD4+ T cells but up-regulated in CD8+ T cells. CD4+ and CD8+ T cell clonal expansion was greater in miR-150-KO mice than in WT mice, but miR-150 selectively repressed IL-2 production in CD4+ T cells. Transcriptome analysis of CD4+ T cells demonstrated that apoptosis and mTOR pathways were highly enriched in the absence of miR-150. Mechanistic studies confirmed that miR-150 promoted apoptosis specifically in antigen-specific CD4+ T cells, but not in bystander CD4+ nor in CD8+ T cells. Furthermore, inhibition of mTOR-linked mitochondrial superoxidedismutase-2 increased apoptosis in miR-150-/- antigen-specific CD4+ T. Thus, miR-150 impacts CD4+ T cell helper activity by attenuating IL-2 production along with clonal expansion, and suppresses superoxidedismutase to promote apoptosis.
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spelling doaj.art-7d33ae2362004c1e8e8efe8f3aca50db2023-02-03T11:50:43ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-01-011410.3389/fimmu.2023.11024031102403Antigen-specific downregulation of miR-150 in CD4 T cells promotes cell survivalAntoine MénoretFederica AglianoTimofey A. KarginovKeaton S. KarlinseyBeiyan ZhouAnthony T. VellaMicroRNA-150 (miR-150) has been shown to play a general role in the immune system, but very little is known about its role on CD4+ T cell responses. During T cell responses against superantigen Staphylococcal Enterotoxin A, miR-150 expression was down-regulated in antigen-specific CD4+ T cells but up-regulated in CD8+ T cells. CD4+ and CD8+ T cell clonal expansion was greater in miR-150-KO mice than in WT mice, but miR-150 selectively repressed IL-2 production in CD4+ T cells. Transcriptome analysis of CD4+ T cells demonstrated that apoptosis and mTOR pathways were highly enriched in the absence of miR-150. Mechanistic studies confirmed that miR-150 promoted apoptosis specifically in antigen-specific CD4+ T cells, but not in bystander CD4+ nor in CD8+ T cells. Furthermore, inhibition of mTOR-linked mitochondrial superoxidedismutase-2 increased apoptosis in miR-150-/- antigen-specific CD4+ T. Thus, miR-150 impacts CD4+ T cell helper activity by attenuating IL-2 production along with clonal expansion, and suppresses superoxidedismutase to promote apoptosis.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1102403/fullMiR-150lymphocytenon-coding RNAsuperantigenmTORapoptosis
spellingShingle Antoine Ménoret
Federica Agliano
Timofey A. Karginov
Keaton S. Karlinsey
Beiyan Zhou
Anthony T. Vella
Antigen-specific downregulation of miR-150 in CD4 T cells promotes cell survival
Frontiers in Immunology
MiR-150
lymphocyte
non-coding RNA
superantigen
mTOR
apoptosis
title Antigen-specific downregulation of miR-150 in CD4 T cells promotes cell survival
title_full Antigen-specific downregulation of miR-150 in CD4 T cells promotes cell survival
title_fullStr Antigen-specific downregulation of miR-150 in CD4 T cells promotes cell survival
title_full_unstemmed Antigen-specific downregulation of miR-150 in CD4 T cells promotes cell survival
title_short Antigen-specific downregulation of miR-150 in CD4 T cells promotes cell survival
title_sort antigen specific downregulation of mir 150 in cd4 t cells promotes cell survival
topic MiR-150
lymphocyte
non-coding RNA
superantigen
mTOR
apoptosis
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1102403/full
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AT keatonskarlinsey antigenspecificdownregulationofmir150incd4tcellspromotescellsurvival
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