Redistribution of the nuclear protein IFI16 into the cytoplasm of ultraviolet B-exposed keratinocytes as a mechanism of autoantigen processing

S. Costa, C. Borgogna, M. Mondini, M. De Andrea, P. L. Meroni, E. Berti, M. Gariglio, Santo Landolfo

Research output: Contribution to journalArticle

Abstract

Summary Background: The skin has long been recognized as a prominent target tissue in systemic lupus erythematosus (SLE) which plays a crucial role in the initiation and perpetuation of the autoimmune reaction cascade as a consequence of ultraviolet (UV)-induced keratinocyte apoptosis. Antibodies against IFI16 (interferon-inducible protein 16) have been detected in the sera of patients with SLE. Objectives To verify whether the induction of autoimmunity against IFI16 involves redistribution of this nuclear protein in keratinocytes during UVB-induced cell death. Methods An in vitro epidermal model was developed to investigate the fate of the IFI16 protein in keratinocytes after irradiation with UVB; both keratinocyte monolayers and human skin explants were used. IFI16 expression and localization were also analysed in diseased skin sections of patients with SLE. Results We demonstrated that IFI16, normally restricted to the nucleus, can be induced to appear in the cytoplasm under conditions of UVB-induced cell injury. This nucleus to cytoplasm translocation was also observed in skin explants exposed to UVB and in the diseased skin sections from patients with SLE. In addition, IFI16 was found in the supernatants of UVB-exposed keratinocytes. Conclusions The finding that IFI16 is present in the cytoplasm of diseased skin cells from patients with SLE and the demonstration of IFI16 in the supernatants of UVB-exposed keratinocytes, suggest that UVB irradiation or other stimuli may favour an abnormal IFI16 presentation to the afferent limb of the immune system and potentially an autoimmune response against the protein itself.

Original languageEnglish
Pages (from-to)282-290
Number of pages9
JournalBritish Journal of Dermatology
Volume164
Issue number2
DOIs
Publication statusPublished - Feb 2011

ASJC Scopus subject areas

  • Dermatology

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