Cell-specific type I IFN signatures in autoimmunity and viral infection: what makes the difference?

PLoS One. 2013 Dec 31;8(12):e83776. doi: 10.1371/journal.pone.0083776. eCollection 2013.


Gene expression profiling of peripheral blood mononuclear cells (PBMCs) has revealed a crucial role for type I interferon (IFN) in the pathogenesis of systemic lupus erythematosus (SLE). However, it is unclear how particular leucocyte subsets contribute to the overall type I IFN signature of PBMCs and whole blood samples.Furthermore, a detailed analysis describing the differences in the IFN signature in autoimmune diseases from that observed after viral infection has not been performed to date. Therefore, in this study, the transcriptional responses in peripheral T helper cells (CD4(+)) and monocyte subsets (CD16(-) inflammatory and CD16(+) resident monocytes) isolated from patients with SLE, healthy donors (ND) immunised with the yellow fever vaccine YFV-17Dand untreated controls were compared by global gene expression profiling.It was striking that all of the transcripts that were regulated in response to viral exposure were also found to be differentially regulated in SLE, albeit with markedly lower fold-change values. In addition to this common IFN signature, a pathogenic IFN-associated gene signature was detected in the CD4(+) T cells and monocytes from the lupus patients. IL-10, IL-9 and IL-15-mediated JAK/STAT signalling was shown to be involved in the pathological amplification of IFN responses observed in SLE. Type I IFN signatures identified were successfully applied for the monitoring of interferon responses in PBMCs of an independent cohort of SLE patients and virus-infected individuals. Moreover, these cell-type specific gene signatures allowed a correct classification of PBMCs independent from their heterogenic cellular composition. In conclusion, our data show for the first time that monocytes and CD4 cells are sensitive biosensors to monitor type I interferon response signatures in autoimmunity and viral infection and how these transriptional responses are modulated in a cell- and disease-specific manner.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoimmunity
  • Biomarkers / metabolism*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • Case-Control Studies
  • Female
  • Gene Expression Profiling
  • Healthy Volunteers
  • Humans
  • Interferon Type I / genetics*
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism*
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Erythematosus, Systemic / immunology
  • Monocytes / immunology
  • Monocytes / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Yellow Fever / genetics*
  • Yellow Fever / immunology
  • Yellow Fever / prevention & control
  • Yellow Fever Vaccine / administration & dosage
  • Yellow fever virus / genetics


  • Biomarkers
  • Interferon Type I
  • RNA, Messenger
  • Yellow Fever Vaccine

Associated data

  • GEO/GSE51997

Grants and funding

This work was supported by the German Ministry of Education and Research (BMBF) within the National Genome Research Network NGFN (01GS0413), the German Research Foundation (Collaborative Research Centre SFB650, TP12), by the European Union's Sixth Framework Programme (project AutoCure; LSHB-CT-2006-018861), and by the IMI JU funded project BeTheCure (contract no 115142-2). Chieko Kyogoku thanks the Alexander von Humboldt Foundation for her fellowship and funding. The funders had no role on study design, data collection and analysis, decision to publish, or preparation of the manuscript.