Cell-specific type I IFN signatures in autoimmunity and viral infection: what makes the difference?
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 a...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3877094?pdf=render |
| _version_ | 1818201343464046592 |
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| author | Chieko Kyogoku Biljana Smiljanovic Joachim R Grün Robert Biesen Ursula Schulte-Wrede Thomas Häupl Falk Hiepe Tobias Alexander Andreas Radbruch Andreas Grützkau |
| author_facet | Chieko Kyogoku Biljana Smiljanovic Joachim R Grün Robert Biesen Ursula Schulte-Wrede Thomas Häupl Falk Hiepe Tobias Alexander Andreas Radbruch Andreas Grützkau |
| author_sort | Chieko Kyogoku |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T02:52:03Z |
| format | Article |
| id | doaj.art-3f26402ddb2e48d1bbf8905fe9dee7d0 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T02:52:03Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-3f26402ddb2e48d1bbf8905fe9dee7d02022-12-22T00:40:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01812e8377610.1371/journal.pone.0083776Cell-specific type I IFN signatures in autoimmunity and viral infection: what makes the difference?Chieko KyogokuBiljana SmiljanovicJoachim R GrünRobert BiesenUrsula Schulte-WredeThomas HäuplFalk HiepeTobias AlexanderAndreas RadbruchAndreas GrützkauGene 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.http://europepmc.org/articles/PMC3877094?pdf=render |
| spellingShingle | Chieko Kyogoku Biljana Smiljanovic Joachim R Grün Robert Biesen Ursula Schulte-Wrede Thomas Häupl Falk Hiepe Tobias Alexander Andreas Radbruch Andreas Grützkau Cell-specific type I IFN signatures in autoimmunity and viral infection: what makes the difference? PLoS ONE |
| title | Cell-specific type I IFN signatures in autoimmunity and viral infection: what makes the difference? |
| title_full | Cell-specific type I IFN signatures in autoimmunity and viral infection: what makes the difference? |
| title_fullStr | Cell-specific type I IFN signatures in autoimmunity and viral infection: what makes the difference? |
| title_full_unstemmed | Cell-specific type I IFN signatures in autoimmunity and viral infection: what makes the difference? |
| title_short | Cell-specific type I IFN signatures in autoimmunity and viral infection: what makes the difference? |
| title_sort | cell specific type i ifn signatures in autoimmunity and viral infection what makes the difference |
| url | http://europepmc.org/articles/PMC3877094?pdf=render |
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