Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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SHR Neuro Krebs Kardio Lipid

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.
miR-181a Modulation of ERK-MAPK Signaling Sustains DC-SIGN Expression and Limits Activation of Monocyte-Derived Dendritic Cells.
Cell Rep. 2020; 30(11): 3793-3805. [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Geiger Olivia
Högenauer Christoph
Lim Clarice
Passegger Christina Angelika
Romberger Johann
Stracke Anika
Strobl Herbert
Zebisch Armin
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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. Copyright © 2020. Published by Elsevier Inc.

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