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

Zhang et al. Immunity 45, 119-130, 2016

Speaker: Yi-Sheng Jiang (江翊生)                       Time: 14:00~15:00, Feb. 22, 2017

Commentator: Dr. Pin Ling (凌斌老師)               Place: Room 601

Abstract:

Type I interferons (IFNs) are polypeptides that are secreted by infected cells and modulate both innate and adaptive immune responses. Type I IFNs play a protective role in acute viral infection. However, Type I IFNs may increase in patients and exacerbate disease severity.¹ Psoriasis is a chronic inflammatory skin disease, which forms red plaques with scales and is characterized by epidermal hyperplasia, immune cell infiltration, and severe angiogenesis.² It has been shown that type I IFN-inducible genes are upregulated in psoriatic lesions. Furthermore, patients treated with type I IFNs often result in more severe psoriasis.³ In this study, the authors demonstrate that keratinocytes, the major cells in interfollicular epidermis, serve as a source of IFN-β in the presence of dsRNAs combined with the antimicrobial peptide LL37. Furthermore, dsRNAs and LL37 stimulate IFN-β production via mitochondrial antiviral-signaling protein (MAVS)-dependent activation of TBK1 (TANK-binding kinase 1)-AKT-IRF3 (interferon regulatory factor 3) signaling pathways. Secreted cytokines, especially IFN-β, activate dendritic cells and initiate downstream immune responses, resulting in more severe skin diseases. Collectively, these results demonstrate how the epidermis responds to skin injury, thus linking innate and adaptive immune responses in skin injury.

References:

1.     González-Navajas JM, Lee J, David M, and Raz E. (2012) Immunomodulatory functions of type I interferons. Nat. Rev. Immunol. 12, 125-135.

2.     Griffiths CE1, Barker JN. (2007) Pathogenesis and clinical features of psoriasis. Lancet 370, 263-271.

3.     Ruano J, Suárez-Fariñas M, Shemer A, Oliva M, Guttman-Yassky E, and Krueger JG. (2016) Molecular and cellular profiling of scalp psoriasis reveals differences and similarities compared to skin psoriasis. Plos One 11, e0148450. doi: 10.1371/journal.pone.0148450.