title: Cell-specific type I IFN signatures in autoimmunity and viral infection: what makes the difference?
abstract: 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.
authors.affiliation: German Rheumatism Research Centre (DRFZ) Berlin, An Institute of the Leibniz Association, Berlin, Germany ; University of Tsukuba Hospital, Amakubo, Tsukuba-shi, Ibaraki-ken, Japan.
authors.forename: Chieko
authors.initials: C
authors.lastname: Kyogoku
authors.affiliation: German Rheumatism Research Centre (DRFZ) Berlin, An Institute of the Leibniz Association, Berlin, Germany.
authors.forename: Biljana
authors.initials: B
authors.lastname: Smiljanovic
authors.affiliation: German Rheumatism Research Centre (DRFZ) Berlin, An Institute of the Leibniz Association, Berlin, Germany.
authors.forename: Joachim R
authors.initials: JR
authors.lastname: Grün
authors.affiliation: German Rheumatism Research Centre (DRFZ) Berlin, An Institute of the Leibniz Association, Berlin, Germany ; Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin, Humboldt University of Berlin, Berlin, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Biesen
authors.affiliation: German Rheumatism Research Centre (DRFZ) Berlin, An Institute of the Leibniz Association, Berlin, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Schulte-Wrede
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin, Humboldt University of Berlin, Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Häupl
authors.affiliation: German Rheumatism Research Centre (DRFZ) Berlin, An Institute of the Leibniz Association, Berlin, Germany ; Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin, Humboldt University of Berlin, Berlin, Germany.
authors.forename: Falk
authors.initials: F
authors.lastname: Hiepe
authors.affiliation: German Rheumatism Research Centre (DRFZ) Berlin, An Institute of the Leibniz Association, Berlin, Germany ; Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin, Humboldt University of Berlin, Berlin, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Alexander
authors.affiliation: German Rheumatism Research Centre (DRFZ) Berlin, An Institute of the Leibniz Association, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Radbruch
authors.affiliation: German Rheumatism Research Centre (DRFZ) Berlin, An Institute of the Leibniz Association, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Grützkau
mesh_terms: D000328:Adult; D015551:Autoimmunity; D015415:Biomarkers / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D064368:Healthy Volunteers; D006801:Humans; D007370:Interferon Type I / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000235:genetics* / Q000276:immunology; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015004:Yellow Fever / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control; D022341:Yellow Fever Vaccine / Q000008:administration & dosage; D015005:Yellow fever virus / Q000235:genetics
chemical_list: D015415:Biomarkers; D007370:Interferon Type I; D012333:RNA, Messenger; D022341:Yellow Fever Vaccine