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

Autor: Melanie Chensee, Nicole L. Ward, Emi Sato, Yi Fritz, Christopher A. Adase, George L. Sen, Nina J. Gao, Ling-juan Zhang, Richard L. Gallo, Michael R. Williams, James A. Sanford, Andrew Johnston, Kimberly A. Chun, Yifang Chen, Tissa Hata, Jaymie Baliwag
Rok vydání: 2015
Předmět:
0301 basic medicine
Keratinocytes
Cellular differentiation
Mice
TANK-binding kinase 1
2.1 Biological and endogenous factors
Immunology and Allergy
Aetiology
RNA
Small Interfering
Cells
Cultured
Skin
Mice
Knockout
Cultured
integumentary system
Adaptor Proteins
Cell Differentiation
Cell biology
Mitochondria
Infectious Diseases
Signal transduction
medicine.symptom
Signal Transduction
Cells
Knockout
1.1 Normal biological development and functioning
Immunology
Inflammation
Biology
Small Interfering
Autoimmune Disease
03 medical and health sciences
Underpinning research
Cathelicidins
medicine
Animals
Humans
Psoriasis
Protein kinase B
Adaptor Proteins
Signal Transducing
Wound Healing
Signal Transducing
Dendritic Cells
Interferon-beta
Emerging Infectious Diseases
030104 developmental biology
RNA
Wounds and Injuries
Epidermis
Wound healing
IRF3
Interferon regulatory factors
Antimicrobial Cationic Peptides
Zdroj: Immunity, vol 45, iss 1
ISSN: 1097-4180
Popis: 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 Kinase1)-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.
Databáze: OpenAIRE
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