miR-181a Modulation of ERK-MAPK Signaling Sustains DC-SIGN Expression and Limits Activation of Monocyte-Derived Dendritic Cells.
Document Type
Article
Publication Date
3-17-2020
Keywords
JGM
JAX Source
Cell Rep 2020 Mar 17; 30:3793-3805.e5
Volume
30
Issue
11
First Page
3793
Last Page
3805
ISSN
2211-1247
PMID
32187550
DOI
https://doi.org/10.1016/j.celrep.2020.02.077
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-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.
Recommended Citation
Lim C,
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 R,
Henao-Mejia J,
Strobl H.
miR-181a Modulation of ERK-MAPK Signaling Sustains DC-SIGN Expression and Limits Activation of Monocyte-Derived Dendritic Cells. Cell Rep 2020 Mar 17; 30:3793-3805.e5