Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Zyulina, V; Yan, KK; Ju, B; Schwarzenberger, E; Passegger, C; Tam-Amersdorfer, C; Pan, Q; Sconocchia, T; Pollack, C; Shaner, B; Zebisch, A; Easton, J; Yu, J; Silva, JM; Strobl, H.
The miR-424(322)/503 gene cluster regulates pro- versus anti-inflammatory skin DC subset differentiation by modulating TGF-β signaling.
Cell Rep. 2021; 35(4): 109049-109049.
Doi: 10.1016/j.celrep.2021.109049
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PubMed
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- Leading authors Med Uni Graz
- Strobl Herbert
- Zyulina Victoria
- Co-authors Med Uni Graz
- Passegger Christina Angelika
- Schwarzenberger Elke
- Sconocchia Tommaso
- Tam-Amersdorfer Carmen
- Zebisch Armin
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- Abstract:
- Transforming growth factor β (TGF-β) family ligands are key regulators of dendritic cell (DC) differentiation and activation. Epidermal Langerhans cells (LCs) require TGF-β family signaling for their differentiation, and canonical TGF-β1 signaling secures a non-activated LC state. LCs reportedly control skin inflammation and are replenished from peripheral blood monocytes, which also give rise to pro-inflammatory monocyte-derived DCs (moDCs). By studying mechanisms in inflammation, we previously screened LCs versus moDCs for differentially expressed microRNAs (miRNAs). This revealed that miR-424/503 is the most strongly inversely regulated (moDCs > LCs). We here demonstrate that miR-424/503 is induced during moDC differentiation and promotes moDC differentiation in human and mouse. Inversely, forced repression of miR-424 during moDC differentiation facilitates TGF-β1-dependent LC differentiation. Mechanistically, miR-424/503 deficiency in monocyte/DC precursors leads to the induction of TGF-β1 response genes critical for LC differentiation. Therefore, the miR-424/503 gene cluster plays a decisive role in anti-inflammatory LC versus pro-inflammatory moDC differentiation from monocytes. Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.