RT Journal Article
SR Electronic
T1 miR-424(322) is a molecular switch controlling pro-inflammatory vs anti-inflammatory skin DC subset differentiation by modulating TGF-β signaling
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.09.07.285627
DO 10.1101/2020.09.07.285627
A1 Victoria Zyulina
A1 Koon-Kiu Yan
A1 Bensheng Ju
A1 Christina Passegger
A1 Carmen Tam-Amersdorfer
A1 Qingfei Pan
A1 Tommaso Sconocchia
A1 Christian Pollack
A1 Bridget Shaner
A1 Armin Zebisch
A1 John Easton
A1 Jiyang Yu
A1 Jose M. Silva
A1 Herbert Strobl
YR 2020
UL http://biorxiv.org/content/early/2020/09/08/2020.09.07.285627.abstract
AB 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). Among all the miRNAs differentially expressed in LC vs moDCs, we observed miR-424 to be strongly induced during moDC differentiation from monocytes. We discovered that miR-424 is required for moDC differentiation from human and murine precursor cells in vitro and for inflammation-associated moDC in vivo. Mechanistically we found that low levels of miR-424 facilitate TGF-β1-dependent LC differentiation at the expense of moDC differentiation. Loss of miR-424 in monocyte/DC precursors resulted in the induction of TGF-β pathway. Therefore, miR-424 plays a decisive role in anti-inflammatory LC vs pro-inflammatory moDC differentiation from monocytes, and its repression allows TGF-β ligands to promote LC differentiation.Short summary Monocytes give rise to two distinct DC subsets in skin inflammation, exhibiting opposite roles in inflammation. This study identified miR-424(322) as a molecular switch controlling pro-inflammatory (moDC) vs anti-inflammatory LC subset differentiation by modulating TGF-β signaling.Competing Interest StatementThe authors have declared no competing interest.Abbreviations usedBMbone marrowBMDCbone marrow-derived dendritic cellsBMP7bone morphogenetic protein 7DCdendritic cellGM-SCFgranulocyte-macrophage colony-stimulating factorIL-4interleukin 4IMQimiquimodKLF4Kruppel-like factor 4LCLangerhans cellmiR-424microRNA-424moDCmonocyte-derived dendritic cellmoPsmonocyte committed progenitor cellsRUNX3runt-related transcription factor 3TGF-β1Transforming growth factor beta 1