| First Author | Montoya MM | Year | 2017 |
| Journal | J Immunol | Volume | 199 |
| Issue | 2 | Pages | 559-569 |
| PubMed ID | 28607111 | Mgi Jnum | J:254392 |
| Mgi Id | MGI:6100043 | Doi | 10.4049/jimmunol.1700170 |
| Citation | Montoya MM, et al. (2017) A Distinct Inhibitory Function for miR-18a in Th17 Cell Differentiation. J Immunol 199(2):559-569 |
| abstractText | 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)gammat(+) Th17 cell differentiation in vitro and increased the number of tissue Th17 cells expressing CCR6, RORgammat, and IL-17A in airway inflammation models in vivo. Sequence-specific miR-18 inhibitors increased CCR6 and RORgammat 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. |
