Reverse interferon signature is characteristic of antigen-presenting cells in human and rat spondyloarthritis

Ingrid Fert, Nicolas Cagnard, Simon Glatigny, Franck Letourneur, Sébastien Jacques, Judith A. Smith, Robert A. Colbert, Joel D. Taurog, Gilles Chiocchia, Luiza M. Araujo, Maxime Breban

Research output: Contribution to journalArticle

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Abstract

Objective In HLA-B27-transgenic rats, the development of a disorder that mimics spondyloarthritis (SpA) is highly correlated with dendritic cell (DC) dysfunction. The present study was undertaken to analyze the underlying mechanisms of this via transcriptome analysis. Methods Transcriptome analysis of ex vivo-purified splenic CD103+CD4+ DCs from B27-transgenic rats and control rats was performed. Transcriptional changes in selected genes were confirmed by quantitative reverse transcriptase-polymerase chain reaction. A meta-analysis of our rat data and published data on gene expression in macrophages from ankylosing spondylitis (AS) patients was further performed. Results Interferon (IFN) signaling was the most significantly affected pathway in DCs from B27-transgenic rats; the majority of genes connected to IFN were underexpressed in B27-transgenic rats as compared to controls. This pattern was already present at disease onset, persisted over time, and was conserved in 2 disease-prone B27-transgenic rat lines. In DCs from B27-transgenic rats, we further found an up-regulation of suppressor of cytokine signaling 3 (which may account for reverse IFN signaling) and a down-regulation of interleukin-27 (a cytokine that opposes Th17 differentiation and promotes Treg cells). The meta-analysis of data on conventional DCs from rats and data on monocyte-derived macrophages from humans revealed 7 IFN-regulated genes that were negatively regulated in both human and rat SpA (i.e., IRF1, STAT1, CXCL9, CXCL10, IFIT3, DDX60, and EPSTI1). Conclusion Our results suggest that expression of HLA-B27 leads to a defect in IFNγ signaling in antigen-presenting cells in both B27-transgenic rats and SpA patients, which may result in Th17 expansion and Treg cell alteration (as shown in B27-transgenic rats) and contribute to disease pathogenesis.

Original languageEnglish (US)
Pages (from-to)841-851
Number of pages11
JournalArthritis and Rheumatology
Volume66
Issue number4
DOIs
StatePublished - 2014

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Transgenic Rats
Antigen-Presenting Cells
Interferons
HLA-B27 Antigen
Gene Expression Profiling
Regulatory T-Lymphocytes
Meta-Analysis
Interleukin-27
Macrophages
Cytokines
Genes
Th17 Cells
Ankylosing Spondylitis
Reverse Transcriptase Polymerase Chain Reaction
Dendritic Cells
Up-Regulation
Down-Regulation
Gene Expression

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology

Cite this

Fert, I., Cagnard, N., Glatigny, S., Letourneur, F., Jacques, S., Smith, J. A., ... Breban, M. (2014). Reverse interferon signature is characteristic of antigen-presenting cells in human and rat spondyloarthritis. Arthritis and Rheumatology, 66(4), 841-851. https://doi.org/10.1002/art.38318

Reverse interferon signature is characteristic of antigen-presenting cells in human and rat spondyloarthritis. / Fert, Ingrid; Cagnard, Nicolas; Glatigny, Simon; Letourneur, Franck; Jacques, Sébastien; Smith, Judith A.; Colbert, Robert A.; Taurog, Joel D.; Chiocchia, Gilles; Araujo, Luiza M.; Breban, Maxime.

In: Arthritis and Rheumatology, Vol. 66, No. 4, 2014, p. 841-851.

Research output: Contribution to journalArticle

Fert, I, Cagnard, N, Glatigny, S, Letourneur, F, Jacques, S, Smith, JA, Colbert, RA, Taurog, JD, Chiocchia, G, Araujo, LM & Breban, M 2014, 'Reverse interferon signature is characteristic of antigen-presenting cells in human and rat spondyloarthritis', Arthritis and Rheumatology, vol. 66, no. 4, pp. 841-851. https://doi.org/10.1002/art.38318
Fert, Ingrid ; Cagnard, Nicolas ; Glatigny, Simon ; Letourneur, Franck ; Jacques, Sébastien ; Smith, Judith A. ; Colbert, Robert A. ; Taurog, Joel D. ; Chiocchia, Gilles ; Araujo, Luiza M. ; Breban, Maxime. / Reverse interferon signature is characteristic of antigen-presenting cells in human and rat spondyloarthritis. In: Arthritis and Rheumatology. 2014 ; Vol. 66, No. 4. pp. 841-851.
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abstract = "Objective In HLA-B27-transgenic rats, the development of a disorder that mimics spondyloarthritis (SpA) is highly correlated with dendritic cell (DC) dysfunction. The present study was undertaken to analyze the underlying mechanisms of this via transcriptome analysis. Methods Transcriptome analysis of ex vivo-purified splenic CD103+CD4+ DCs from B27-transgenic rats and control rats was performed. Transcriptional changes in selected genes were confirmed by quantitative reverse transcriptase-polymerase chain reaction. A meta-analysis of our rat data and published data on gene expression in macrophages from ankylosing spondylitis (AS) patients was further performed. Results Interferon (IFN) signaling was the most significantly affected pathway in DCs from B27-transgenic rats; the majority of genes connected to IFN were underexpressed in B27-transgenic rats as compared to controls. This pattern was already present at disease onset, persisted over time, and was conserved in 2 disease-prone B27-transgenic rat lines. In DCs from B27-transgenic rats, we further found an up-regulation of suppressor of cytokine signaling 3 (which may account for reverse IFN signaling) and a down-regulation of interleukin-27 (a cytokine that opposes Th17 differentiation and promotes Treg cells). The meta-analysis of data on conventional DCs from rats and data on monocyte-derived macrophages from humans revealed 7 IFN-regulated genes that were negatively regulated in both human and rat SpA (i.e., IRF1, STAT1, CXCL9, CXCL10, IFIT3, DDX60, and EPSTI1). Conclusion Our results suggest that expression of HLA-B27 leads to a defect in IFNγ signaling in antigen-presenting cells in both B27-transgenic rats and SpA patients, which may result in Th17 expansion and Treg cell alteration (as shown in B27-transgenic rats) and contribute to disease pathogenesis.",
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T1 - Reverse interferon signature is characteristic of antigen-presenting cells in human and rat spondyloarthritis

AU - Fert, Ingrid

AU - Cagnard, Nicolas

AU - Glatigny, Simon

AU - Letourneur, Franck

AU - Jacques, Sébastien

AU - Smith, Judith A.

AU - Colbert, Robert A.

AU - Taurog, Joel D.

AU - Chiocchia, Gilles

AU - Araujo, Luiza M.

AU - Breban, Maxime

PY - 2014

Y1 - 2014

N2 - Objective In HLA-B27-transgenic rats, the development of a disorder that mimics spondyloarthritis (SpA) is highly correlated with dendritic cell (DC) dysfunction. The present study was undertaken to analyze the underlying mechanisms of this via transcriptome analysis. Methods Transcriptome analysis of ex vivo-purified splenic CD103+CD4+ DCs from B27-transgenic rats and control rats was performed. Transcriptional changes in selected genes were confirmed by quantitative reverse transcriptase-polymerase chain reaction. A meta-analysis of our rat data and published data on gene expression in macrophages from ankylosing spondylitis (AS) patients was further performed. Results Interferon (IFN) signaling was the most significantly affected pathway in DCs from B27-transgenic rats; the majority of genes connected to IFN were underexpressed in B27-transgenic rats as compared to controls. This pattern was already present at disease onset, persisted over time, and was conserved in 2 disease-prone B27-transgenic rat lines. In DCs from B27-transgenic rats, we further found an up-regulation of suppressor of cytokine signaling 3 (which may account for reverse IFN signaling) and a down-regulation of interleukin-27 (a cytokine that opposes Th17 differentiation and promotes Treg cells). The meta-analysis of data on conventional DCs from rats and data on monocyte-derived macrophages from humans revealed 7 IFN-regulated genes that were negatively regulated in both human and rat SpA (i.e., IRF1, STAT1, CXCL9, CXCL10, IFIT3, DDX60, and EPSTI1). Conclusion Our results suggest that expression of HLA-B27 leads to a defect in IFNγ signaling in antigen-presenting cells in both B27-transgenic rats and SpA patients, which may result in Th17 expansion and Treg cell alteration (as shown in B27-transgenic rats) and contribute to disease pathogenesis.

AB - Objective In HLA-B27-transgenic rats, the development of a disorder that mimics spondyloarthritis (SpA) is highly correlated with dendritic cell (DC) dysfunction. The present study was undertaken to analyze the underlying mechanisms of this via transcriptome analysis. Methods Transcriptome analysis of ex vivo-purified splenic CD103+CD4+ DCs from B27-transgenic rats and control rats was performed. Transcriptional changes in selected genes were confirmed by quantitative reverse transcriptase-polymerase chain reaction. A meta-analysis of our rat data and published data on gene expression in macrophages from ankylosing spondylitis (AS) patients was further performed. Results Interferon (IFN) signaling was the most significantly affected pathway in DCs from B27-transgenic rats; the majority of genes connected to IFN were underexpressed in B27-transgenic rats as compared to controls. This pattern was already present at disease onset, persisted over time, and was conserved in 2 disease-prone B27-transgenic rat lines. In DCs from B27-transgenic rats, we further found an up-regulation of suppressor of cytokine signaling 3 (which may account for reverse IFN signaling) and a down-regulation of interleukin-27 (a cytokine that opposes Th17 differentiation and promotes Treg cells). The meta-analysis of data on conventional DCs from rats and data on monocyte-derived macrophages from humans revealed 7 IFN-regulated genes that were negatively regulated in both human and rat SpA (i.e., IRF1, STAT1, CXCL9, CXCL10, IFIT3, DDX60, and EPSTI1). Conclusion Our results suggest that expression of HLA-B27 leads to a defect in IFNγ signaling in antigen-presenting cells in both B27-transgenic rats and SpA patients, which may result in Th17 expansion and Treg cell alteration (as shown in B27-transgenic rats) and contribute to disease pathogenesis.

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