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MYC-mediated silencing of miR-181a-5p promotes pathogenic Th17 responses by modulating AKT3-FOXO3 signaling.

ABSTRACT: Pathogenic Th17 cells drive autoimmune pathology, but the molecular mechanisms underlying Th17 pathogenicity remain poorly understood. Here, we have shown that miR-181a-5p was significantly decreased in pathogenic Th17 cells, and it negatively regulated pathogenic Th17 cell responses in vitro and in vivo. Th17 cells overexpressing miR-181a-5p exhibited impaired ability to induce pathogenesis in an adoptive transfer model of experimental autoimmune uveitis (EAU). Mechanistically, miR-181a-5p directly targeted AKT3, diminishing AKT3-mediated phosphorylation of FOXO3, and thereby activating FOXO3, a transcriptional repressor of pathogenic Th17 cell program. Supporting this, decreasing miR-181a-5p and up-regulated AKT3 expression were found in uveitis patients. Furthermore, intravitreal administration of miR-181a-5p mimics in mice effectively attenuated clinical and pathological signs of established EAU. Collectively, our results reveal a previously unappreciated T cell-intrinsic role of miR-181a-5p in restraining autoimmunity and may provide a potential therapeutic target for uveitis treatment.

SUBMITTER: Chen S

PROVIDER: S-EPMC9557906 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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MYC-mediated silencing of miR-181a-5p promotes pathogenic Th17 responses by modulating AKT3-FOXO3 signaling.

Chen Sisi S Ma Binyun B Li Xue X Zhang Kailang K Wei Yankai Y Du Bei B Liu Xun X Wei Ruihua R Li Xiaorong X Nian Hong H

iScience 20220923 10

Pathogenic Th17 cells drive autoimmune pathology, but the molecular mechanisms underlying Th17 pathogenicity remain poorly understood. Here, we have shown that miR-181a-5p was significantly decreased in pathogenic Th17 cells, and it negatively regulated pathogenic Th17 cell responses <i>in vitro</i> and <i>in vivo</i>. Th17 cells overexpressing miR-181a-5p exhibited impaired ability to induce pathogenesis in an adoptive transfer model of experimental autoimmune uveitis (EAU). Mechanistically, mi ...[more]

PMID: 36248732

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Dataset Information

MYC-mediated silencing of miR-181a-5p promotes pathogenic Th17 responses by modulating AKT3-FOXO3 signaling.

Publications

MYC-mediated silencing of miR-181a-5p promotes pathogenic Th17 responses by modulating AKT3-FOXO3 signaling.

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