Antimicrobial Peptide LL37 and MAVS Signaling Drive Interferon-β Production by Epidermal Keratinocytes during Skin Injury
In: Immunity, Jg. 45 (2016-07-01), Heft 1
academicJournal
- 119 - 130
Zugriff:
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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Antimicrobial Peptide LL37 and MAVS Signaling Drive Interferon-β Production by Epidermal Keratinocytes during Skin Injury
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Autor/in / Beteiligte Person: | Zhang, Ling-juan ; Sen, George L ; Ward, Nicole L ; Johnston, Andrew ; Chun, Kimberly ; Chen, Yifang ; Adase, Christopher ; Sanford, James A ; Gao, Nina ; Chensee, Melanie ; Sato, Emi ; Fritz, Yi ; Baliwag, Jaymie ; Williams, Michael R ; Hata, Tissa ; Gallo, Richard L |
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Zeitschrift: | Immunity, Jg. 45 (2016-07-01), Heft 1 |
Veröffentlichung: | eScholarship, University of California, 2016 |
Medientyp: | academicJournal |
Umfang: | 119 - 130 |
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