Antimicrobial Peptide LL37 and MAVS Signaling Drive Interferon-ß Production by Epidermal Keratinocytes during Skin Injury.
Immunity
; 45(1): 119-30, 2016 07 19.
Article
in En
| MEDLINE
| ID: mdl-27438769
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-ß was abundantly produced by epidermal keratinocytes (KCs) in psoriasis and during wound repair. KC IFN-ß 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-ß production and then promoted maturation of dendritic cells. In mice, the production of epidermal IFN-ß by LL37 required MAVS, and human wounded and/or psoriatic skin showed activation of MAVS-associated IRF3 and induction of MAVS and IFN-ß gene signatures. These findings show that KCs are an important source of IFN-ß and MAVS is critical to this function, and demonstrates how the epidermis triggers unwanted skin inflammation under disease conditions.
Full text:
1
Database:
MEDLINE
Main subject:
Psoriasis
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Wounds and Injuries
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Dendritic Cells
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Keratinocytes
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Epidermis
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Cathelicidins
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Mitochondria
Limits:
Animals
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Humans
Language:
En
Year:
2016
Type:
Article