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

Montoya, Misty M.; Maul, Julia; Singh, Priti B.; Pua, Heather H.; Dahlström, Frank; Wu, Nanyan; Huang, Xiaozhu; Ansel, K. Mark und Baumjohann, Dirk (2017): A Distinct Inhibitory Function for miR-18a in Th17 Cell Differentiation. In: Journal of Immunology, Bd. 199, Nr. 2: S. 559-569

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) gamma t(+) Th17 cell differentiation in vitro and increased the number of tissue Th17 cells expressing CCR6, ROR gamma t, and IL-17A in airway inflammation models in vivo. Sequence-specific miR-18 inhibitors increased CCR6 and RORgt 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0022-1767
• Sprache: Englisch