RT Journal Article
SR Electronic
T1 A Distinct Inhibitory Function for miR-18a in Th17 Cell Differentiation
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 559
OP 569
DO 10.4049/jimmunol.1700170
VO 199
IS 2
A1 Montoya, Misty M.
A1 Maul, Julia
A1 Singh, Priti B.
A1 Pua, Heather H.
A1 Dahlström, Frank
A1 Wu, Nanyan
A1 Huang, Xiaozhu
A1 Ansel, K. Mark
A1 Baumjohann, Dirk
YR 2017
UL http://www.jimmunol.org/content/199/2/559.abstract
AB 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)γt+ Th17 cell differentiation in vitro and increased the number of tissue Th17 cells expressing CCR6, RORγt, and IL-17A in airway inflammation models in vivo. Sequence-specific miR-18 inhibitors increased CCR6 and RORγt 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.