Lim, Clarice X. and Lee, Bernett and Geiger, Olivia and Passegger, Christina and Beitzinger, Michaela and Romberger, Johann and Stracke, Anika and Hoegenauer, Christoph and Stift, Anton and Stoiber, Heribert and Poidinger, Michael and Zebisch, Armin and Meister, Gunter and Williams, Adam and Flavell, Richard A. and Henao-Mejia, Jorge and Strobl, Herbert (2020) miR-181a Modulation of ERK-MAPK Signaling Sustains DC-SIGN Expression and Limits Activation of Monocyte-Derived Dendritic Cells. CELL REPORTS, 30 (11). 3793-+. ISSN 2211-1247,
Full text not available from this repository. (Request a copy)Abstract
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 microRNA, 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-SIGN(hi) mo-DCs and lead to development of proinflammatory DC-SIGN(Io/-) 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | STEADY-STATE; TGF-BETA; DIFFERENTIATION; MACROPHAGES; RECEPTOR; TARGETS; PROGENITORS; POPULATIONS; INFECTION; ORIGINS; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I > Prof. Dr. Gunter Meister |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Mar 2021 10:10 |
| Last Modified: | 29 Mar 2021 10:10 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44917 |
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