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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02026

Transcriptomic and epigenetic alterations in dendritic cells correspond with chronic kidney disease in lupus nephritis

 Anna Wardowska1, 2*,  Michał Komorniczak3, Barbara Bułło-Piontecka3, M.Alicja Dębska-Ślizień3 and Michał Pikuła4, 5
  • 1Medical University of Gdansk, Poland
  • 2Other, Poland
  • 3Department of Nephrology, Transplantology and Internal Diseases, Faculty of Medicine, Medical University of Gdansk, Poland
  • 4Medical University of Gdansk, Poland
  • 5Clinical Immunology and Transplantology Unit, Department of Immunology, Medical University of Gdansk, Poland

Systemic lupus erythematosus (SLE) is a serious autoimmune disease with variety of organ manifestations. The most dreadful one, affecting the majority of SLE patients, is kidney manifestation – lupus nephritis (LN). Dendritic cells (DC) are believed to be one of the culprits of immune dysregulation in LN. Flow cytometry analysis was applied to identify the frequency and activity of peripheral blood DCs subpopulations: myeloid and plasmacytoid, in LN patients. Magnetically isolated mDCs and pDCs were subjected to molecular analysis of genes expression, evaluation of global DNA methylation and histone H3 methylation. We observed distinctive features of DCs associated with the stages of nephritis in LN patients. Lower numbers of pDCs were observed in patients with severe LN, while increased costimulatory potential of mDCs was connected with early, mild stage of this disease. IRF1 transcript upregulation was specific for mDCs from total LN patients, while exceptional amounts of IRF1 mRNA was detected in mDCs from severe LN patients. DCs DNA hypermethylation seemed characteristic for severe LN, whereas decrease in H3K4me3 and H3K27me3 marks was significant for early stages of LN. These findings present dendritic cell alterations that may reflect renal involvement in SLE, laying foundations for new strategy of diagnosis and monitoring of LN patients, omitting invasive kidney biopsies.

Keywords: dendritic cells, , DNA methylation (5mC), histone modifications., Interferon Regulatory Factors, Chronic Kidney Disease, systemic lupus erythematosus

Received: 04 Jun 2019; Accepted: 12 Aug 2019.

Copyright: © 2019 Wardowska, Komorniczak, Bułło-Piontecka, Dębska-Ślizień and Pikuła. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. Anna Wardowska, Medical University of Gdansk, Gdańsk, Poland,