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| Status |
Public on Mar 10, 2020 |
| Title |
Identification of miR-181a target mRNAs by RIP-CHIP during terminal differentiation of DC-SIGN+ mo-DCs |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
DC-SIGN+ monocyte-derived dendritic cells (mo-DCs) play important roles in bacterial infections and inflammatory diseases, but the factors regulating their differentiation and proinflammatory status remain poorly defined. Here, we identify a micro-RNA, miR-181a, and a molecular mechanism that simultaneously regulate the acquisition of DC-SIGN+ expression and the activation state of DC-SIGN+ mo-DCs. Specifically, we show that miR-181a promotes DC-SIGN expression during terminal mo-DC differentiation and limits its sensitivity and responsiveness to TLR triggering and CD40 ligation. Mechanistically, miR-181a sustains ERK-MAPK signaling in mo-DCs, thereby enabling the maintenance of high levels of DC-SIGN and a high activation threshold. Low miR-181a levels during mo-DC differentiation, induced by inflammatory signals, do not support the high phospho-ERK signal transduction required for DC-SIGNhi mo-DCs and lead to development of proinflammatory DC-SIGNlo/- mo-DCs. Collectively, our study demonstrates that high DC-SIGN expression levels and a high activation threshold in mo-DCs are linked and simultaneously maintained by miR-181a.
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| Overall design |
RIP-CHIP (RNA-Binding Protein Immunoprecipitation-Microarray (Chip) Profiling) was performed to identify miR-181a specific target genes and delineate the Ago-2 dependent miRNA-targetome during terminal differentiation of DC-SIGN+ mo-DCs. Here, CD14+ monocyte intermediates (designated progenitor cell-derived monocytes, or moPs) arising in cultures of cord blood CD34+ progenitor cells were transduced with miR-181a KD or scramble control vectors, and supplemented with GM-CSF and IL-4 for 24 hours; then Ago-2-dependent miRNAs and their associated target mRNAs were pulled down, isolated, and analyzed on Affymetrix microarray chips.
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| Contributor(s) |
Lim CX, Lee B, Geiger O, Passegger C, Beitzinger M, Romberger J, Stracke A, Högenauer C, Stift A, Stoiber H, Poidinger M, Zebisch A, Meister G, Williams A, Flavell RA, Henao-Mejia J, Strobl H |
| Citation(s) |
32187550 |
| Submission date |
Mar 21, 2017 |
| Last update date |
Mar 25, 2020 |
| Contact name |
Bernett Lee |
| E-mail(s) |
bernett_lee@immunol.a-star.edu.sg
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| Organization name |
Singapore Immunology Network
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| Street address |
8A Biomedical Grove #03-06 Immunos
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| City |
NA |
| ZIP/Postal code |
138648 |
| Country |
Singapore |
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| Platforms (1) |
| GPL16686 |
[HuGene-2_0-st] Affymetrix Human Gene 2.0 ST Array [transcript (gene) version] |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA379915 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE96847_RAW.tar |
45.6 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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