Transcriptomics,Multiomics

Dataset Information

50

The multifaceted balance of TNF-a and type I / II interferon responses in SLE and RA: how monocytes manage the impact of cytokines


ABSTRACT: Many cytokines are involved in the pathogenesis of autoimmune diseases and are recognized as relevant therapeutic targets to attenuate inflammation, such as TNFα in RA and IFNα/γ in SLE. To relate the transcriptional imprinting of cytokines in a cell type-specific and disease-specific manner, we generated gene-expression profiles from peripheral monocytes of SLE and RA patients and compared them to in vitro-generated signatures induced by TNFα, IFNα2a and IFNγ. Monocytes from SLE and RA patients revealed disease-specific gene-expression profiles. In vitro-generated signatures induced by IFNα2a and IFNγ showed similar profiles that only partially overlapped with those induced by TNFα. Comparisons between disease-specific and in vitro-generated signatures identified cytokine-regulated genes in SLE and RA with qualitative and quantitative differences. The IFN-responses in SLE and RA were found to be regulated in a STAT1-dependent and STAT1-independent manner, respectively. Similarly, genes recognized as TNFα-regulated were clearly distinguishable between RA and SLE patients. While the activity of SLE monocytes was mainly driven by IFN, the activity from RA monocytes showed a dominance of TNFα that was characterized by STAT1 down-regulation. The responses to specific cytokines were revealed to be disease-dependent and reflected the interplay of cytokines within various inflammatory milieus. This study has demonstrated that monocytes from RA and SLE patients exhibit disease-specific gene-expression profiles, which can be molecularly dissected when compared to in vitro-generated cytokine signatures. The results suggest that an assessment of cytokine-response status in monocytes may be helpful for improvement of diagnosis and selection of the best cytokine target for therapeutic intervention. Expression profiles of human peripheral blood monocytes activated in vivo and stimulated in vitro. Monocytes from patients with SLE and RA and from healthy donors were used for generating disease-specific gene-expression profiles, where these profiles represent in vivo activation of monocytes. In addition, monocytes from healthy donors were stimulated in vitro by cytokines: TNFα, IFNα2a and IFNγ. Cytokine-specific gene-expression profiles were generated by comparing stimulated monocytes with unstimulated ones. TNFα-, IFNα2a- and IFNγ as cytokine-specific gene-expression profiles were compared with RA and SLE, as disease-specific gene-expression profiles.

REANALYSED by: E-GEOD-38351

ORGANISM(S): Homo sapiens  

SUBMITTER: Gerd-R Burmester  Ria Baumgrass   Bruno Stuhlmüller   Ursula Schulte-Wrede   Joachim R Grün   Robert Biesen   Wlodzimierz Maslinski   Andreas Radbruch   Falk Hiepe   Andreas Grützkau   Thomas Häupl   Biljana Smiljanovic    

PROVIDER: E-GEOD-38351 | ArrayExpress | 2015-09-28

SECONDARY ACCESSION(S): GSE38351PRJNA168483

REPOSITORIES: GEO, ArrayExpress

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Publications

The multifaceted balance of TNF-α and type I/II interferon responses in SLE and RA: how monocytes manage the impact of cytokines.

Smiljanovic Biljana B   Grün Joachim R JR   Biesen Robert R   Schulte-Wrede Ursula U   Baumgrass Ria R   Stuhlmüller Bruno B   Maslinski Wlodzimierz W   Hiepe Falk F   Burmester Gerd-R GR   Radbruch Andreas A   Häupl Thomas T   Grützkau Andreas A  

Journal of molecular medicine (Berlin, Germany) 20120519 11


Many cytokines are involved in the pathogenesis of autoimmune diseases and are recognized as relevant therapeutic targets to attenuate inflammation, such as tumor necrosis factor (TNF)-α in rheumatoid arthritis (RA) and interferon (IFN)-α/γ in systemic lupus erythematosus (SLE). To relate the transcriptional imprinting of cytokines in a cell type- and disease-specific manner, we generated gene expression profiles from peripheral monocytes of SLE and RA patients and compared them to in vitro-gene  ...[more]

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