Format

Send to

Choose Destination
Immunity. 2016 Jul 19;45(1):119-30. doi: 10.1016/j.immuni.2016.06.021.

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

Author information

1
Department of Dermatology, University of California, San Diego, La Jolla, CA 92093, USA.
2
Department of Dermatology, University of California, San Diego, La Jolla, CA 92093, USA; Department of Cellular and Molecular Medicine, San Diego, La Jolla, CA 92093, USA.
3
Department of Dermatology, Case Western Reserve University, Cleveland, OH 44106, USA.
4
Department of Dermatology, University of Michigan, Ann Arbor, MI 48109, USA.
5
Department of Dermatology, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: rgallo@ucsd.edu.

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.

PMID:
27438769
PMCID:
PMC4957248
DOI:
10.1016/j.immuni.2016.06.021
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center