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Antimicrobial Peptide LL37 and MAVS Signaling Drive Interferon-β Production by Epidermal Keratinocytes during Skin Injury.

Authors
  • Lj, Zhang
  • Gl, Sen
  • Nl, Ward
  • A, Johnston
  • K, Chun
  • Y, Chen
  • C, Adase
  • Jeremy Sanford
  • N, Gao
  • M, Chensee
  • E, Sato
  • Y, Fritz
  • J, Baliwag
  • Mr, Williams
  • T, Hata
  • Rl, Gallo
Type
Published Article
Journal
Immunity
Publisher
Elsevier
Volume
45
Issue
1
Pages
119–130
Identifiers
DOI: 10.1016/j.immuni.2016.06.021
Source
UCSC Bioinformatics biomedical-ucsc
License
Unknown

Abstract

Type 1 interferons (IFNs) promote inflammation in the skin but the mechanisms responsible for inducing these cytokines are not well understood. We found that IFN-β was abundantly produced by epidermal keratinocytes (KCs) in psoriasis and during wound repair. KC IFN-β production depended on stimulation of mitochondrial antiviral-signaling protein (MAVS) by the antimicrobial peptide LL37 and double stranded-RNA released from necrotic cells. MAVS activated downstream TBK1 (TANK-Binding Kinase 1)-AKT (AKT serine/threonine kinase 1)-IRF3 (interferon regulatory factor 3) signaling cascade leading to IFN-β production and then promoted maturation of dendritic cells. In mice, the production of epidermal IFN-β by LL37 required MAVS, and human wounded and/or psoriatic skin showed activation of MAVS-associated IRF3 and induction of MAVS and IFN-β gene signatures. These findings show that KCs are an important source of IFN-β and MAVS is critical to this function, and demonstrates how the epidermis triggers unwanted skin inflammation under disease conditions.

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