Title | Let-7 microRNAs target the lineage-specific transcription factor PLZF to regulate terminal NKT cell differentiation and effector function. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Pobezinsky, LA, Etzensperger, R, Jeurling, S, Alag, A, Kadakia, T, McCaughtry, TM, Kimura, MY, Sharrow, SO, Guinter, TI, Feigenbaum, L, Singer, A |
Journal | Nat Immunol |
Volume | 16 |
Issue | 5 |
Pagination | 517-24 |
Date Published | 2015 May |
Abstract | Lethal-7 (let-7) microRNAs (miRNAs) are the most abundant miRNAs in the genome, but their role in developing thymocytes is unclear. We found that let-7 miRNAs targeted Zbtb16 mRNA, which encodes the lineage-specific transcription factor PLZF, to post-transcriptionally regulate PLZF expression and thereby the effector functions of natural killer T cells (NKT cells). Dynamic upregulation of let-7 miRNAs during the development of NKT thymocytes downregulated PLZF expression and directed their terminal differentiation into interferon-γ (IFN-γ)-producing NKT1 cells. Without upregulation of let-7 miRNAs, NKT thymocytes maintained high PLZF expression and terminally differentiated into interleukin 4 (IL-4)-producing NKT2 cells or IL-17-producing NKT17 cells. Upregulation of let-7 miRNAs in developing NKT thymocytes was signaled by IL-15, vitamin D and retinoic acid. Such targeting of a lineage-specific transcription factor by miRNA represents a previously unknown level of developmental regulation in the thymus. |
Alternate Journal | Nat. Immunol. |
Veterinary and Animal Sciences