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Human endogenous retrovirus expression is inversely related with the up-regulation of interferon-inducible genes in the skin of patients with lichen planus

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Abstract

Lichen planus (LP) is a common inflammatory skin disease of unknown etiology. Reports of a common transactivation of quiescent human endogenous retroviruses (HERVs) support the connection of viruses to the disease. HERVs are ancient retroviral sequences in the human genome and their transcription is often deregulated in cancer and autoimmune diseases. We explored the transcriptional activity of HERV sequences as well as the antiviral restriction factor and interferon-inducible genes in the skin from LP patients and healthy control (HC) donors. The study included 13 skin biopsies from patients with LP and 12 controls. Real-time PCR assay identified significant decrease in the HERV-K gag and env mRNA expression levels in LP subjects, when compared to control group. The expressions of HERV-K18 and HERV-W env were also inhibited in the skin of LP patients. We observed a strong correlation between HERV-K gag with other HERV sequences, regardless the down-modulation of transcripts levels in LP group. In contrast, a significant up-regulation of the cytidine deaminase APOBEC 3G (apolipoprotein B mRNA-editing), and the GTPase MxA (Myxovirus resistance A) mRNA expression level was identified in the LP skin specimens. Other transcript expressions, such as the master regulator of type I interferon-dependent immune responses, STING (stimulator of interferon genes) and IRF-7 (interferon regulatory factor 7), IFN-β and the inflammassome NALP3, had increased levels in LP, when compared to HC group. Our study suggests that interferon-inducible factors, in addition to their role in innate immunity against exogenous pathogens, contribute to the immune control of HERVs. Evaluation of the balance between HERV and interferon-inducible factor expression could possibly contribute to surveillance of inflammatory/malignant status of skin diseases.

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Acknowledgments

We are grateful to all individuals who participated in the study. This work was supported by Fundação de Amparo a Pesquisa do Estado de São Paulo (2011/20740-3) and the Laboratório de Investigação Médica, Unidade 56 do Hospital das Clínicas da Faculdade de Medicina de São Paulo.

Conflict of interest

None declared.

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Authors and Affiliations

  1. Department of Dermatology, Laboratory of Dermatology and Immunodeficiencies, LIM-56, Medical School of the University of São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 500, 3rd floor, São Paulo, 05403-000, Brazil

    Nátalli Zanete Pereira, Gabriel Costa de Carvalho, Rosana Domingues & Maria Notomi Sato

  2. Dermatological Outpatient Clinic, Hospital das Clínicas, Medical School of the University of São Paulo, São Paulo, Brazil

    Marcelle Almeida de Sousa Nogueira, Camila Fátima Biancardi Gavioli & Valéria Aoki

Authors
  1. Marcelle Almeida de Sousa Nogueira
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  2. Camila Fátima Biancardi Gavioli
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  3. Nátalli Zanete Pereira
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  4. Gabriel Costa de Carvalho
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  7. Maria Notomi Sato
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Corresponding author

Correspondence to Maria Notomi Sato.

Additional information

M. A. de Sousa Nogueira and C. F. Biancardi Gavioli contributed equally to this work.

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de Sousa Nogueira, M.A., Biancardi Gavioli, C.F., Pereira, N.Z. et al. Human endogenous retrovirus expression is inversely related with the up-regulation of interferon-inducible genes in the skin of patients with lichen planus. Arch Dermatol Res 307, 259–264 (2015). https://doi.org/10.1007/s00403-014-1524-0

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  • DOI: https://doi.org/10.1007/s00403-014-1524-0

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