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A Distinct Inhibitory Function for miR-18a in Th17 Cell Differentiation.


ABSTRACT: Th17 cell responses orchestrate immunity against extracellular pathogens but also underlie autoimmune disease pathogenesis. In this study, we uncovered a distinct and critical role for miR-18a in limiting Th17 cell differentiation. miR-18a was the most dynamically upregulated microRNA of the miR-17-92 cluster in activated T cells. miR-18a deficiency enhanced CCR6+ RAR-related orphan receptor (ROR)?t+ Th17 cell differentiation in vitro and increased the number of tissue Th17 cells expressing CCR6, ROR?t, and IL-17A in airway inflammation models in vivo. Sequence-specific miR-18 inhibitors increased CCR6 and ROR?t expression in mouse and human CD4+ T cells, revealing functional conservation. miR-18a directly targeted Smad4, Hif1a, and Rora, all key transcription factors in the Th17 cell gene-expression program. These findings indicate that activating signals influence the outcome of Th cell differentiation via differential regulation of mature microRNAs within a common cluster.

SUBMITTER: Montoya MM 

PROVIDER: S-EPMC5508756 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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A Distinct Inhibitory Function for miR-18a in Th17 Cell Differentiation.

Montoya Misty M MM   Maul Julia J   Singh Priti B PB   Pua Heather H HH   Dahlström Frank F   Wu Nanyan N   Huang Xiaozhu X   Ansel K Mark KM   Baumjohann Dirk D  

Journal of immunology (Baltimore, Md. : 1950) 20170612 2


Th17 cell responses orchestrate immunity against extracellular pathogens but also underlie autoimmune disease pathogenesis. In this study, we uncovered a distinct and critical role for miR-18a in limiting Th17 cell differentiation. miR-18a was the most dynamically upregulated microRNA of the miR-17-92 cluster in activated T cells. miR-18a deficiency enhanced CCR6<sup>+</sup> RAR-related orphan receptor (ROR)γt<sup>+</sup> Th17 cell differentiation in vitro and increased the number of tissue Th17  ...[more]

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