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