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. 2015 Mar;16(2):170-5.
doi: 10.1038/gene.2014.64. Epub 2014 Nov 20.

Activation of the JAK/STAT pathway in Behcet's disease

A Tulunay  1 , M G Dozmorov  2 , F Ture-Ozdemir  1 , V Yilmaz  3 , E Eksioglu-Demiralp  1 , F Alibaz-Oner  4 , G Ozen  4 , J D Wren  5 , G Saruhan-Direskeneli  3 , A H Sawalha  6 , H Direskeneli  4
Affiliations

Activation of the JAK/STAT pathway in Behcet's disease

A Tulunay et al. Genes Immun. 2015 Mar.

Erratum in

  • Activation of the JAK/STAT pathway in Behcet's disease.
    Tulunay A, Dozmorov MG, Ture-Ozdemir F, Yilmaz V, Eksioglu-Demiralp E, Alibaz-Oner F, Ozen G, Wren JD, Saruhan-Direskeneli G, Sawalha AH, Direskeneli H. Tulunay A, et al. Genes Immun. 2015 Mar;16(2):176. doi: 10.1038/gene.2014.80. Genes Immun. 2015. PMID: 25739881 No abstract available.

Abstract

Th1/Th17-type T-cell responses are upregulated in Behcet's disease (BD). However, signaling pathways associated with this aberrant immune response are not clarified. Whole-genome microarray profiling was performed with human U133 (Plus 2.0) chips using messenger RNA of isolated CD14(+) monocytes and CD4(+) T cells from peripheral blood mononucleated cell (PBMC) in patients with BD (n = 9) and healthy controls (HCs) (n = 9). Flow cytometric analysis of unstimulated (US) and stimulated (phytohaemagglutinin) signal transducer and activator of transcription (STAT3) and pSTAT3 expressions of PBMCs were also analyzed (BD and HC, both n = 26). Janus family of kinase (JAK1) was observed to be upregulated in both CD14(+) monocytes (1.95-fold) and CD4(+) T lymphocytes (1.40-fold) of BD patients. Using canonical pathway enrichment analysis, JAK/STAT signaling was identified as activated in both CD14(+) monocytes (P = 9.55E-03) and in CD4(+) lymphocytes (P =8.13E-04) in BD. Interferon signaling was also prominent among upregulated genes in CD14(+) monocytes (P = 5.62E-05). Glucocorticoid receptor signaling and interleukin (IL-6) signaling were among the most enriched pathways in differentially expressed genes in CD14+ monocytes (P = 2.45E-09 and 1.00E-06, respectively). Basal US total STAT3 expression was significantly higher in BD (1.2 vs 3.45, P < 0.05). The JAK1/STAT3 signaling pathway is activated in BD, possibly through the activation of Th1/Th17-type cytokines such as IL-2, interferon (IFN-γ), IL-6, IL-17 and IL-23.

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Conflict of interest statement

CONFLICT OF INTEREST

The authors declare no conflict of interest

Figures

Figure 1
Figure 1
Canonical pathways activated in CD14+ monocytes in Behcet’s disease. Fig1A: JAK/STAT signaling pathway, Fig. 1B: Interferon signaling pathway, Fig. 1C: Interleukin-6 signaling pathway. Red color indicates genes that are upregulated in patients compared to controls.
Figure 1
Figure 1
Canonical pathways activated in CD14+ monocytes in Behcet’s disease. Fig1A: JAK/STAT signaling pathway, Fig. 1B: Interferon signaling pathway, Fig. 1C: Interleukin-6 signaling pathway. Red color indicates genes that are upregulated in patients compared to controls.
Figure 1
Figure 1
Canonical pathways activated in CD14+ monocytes in Behcet’s disease. Fig1A: JAK/STAT signaling pathway, Fig. 1B: Interferon signaling pathway, Fig. 1C: Interleukin-6 signaling pathway. Red color indicates genes that are upregulated in patients compared to controls.
Figure 2
Figure 2
STAT3 and pSTAT3 expressions in PBMCs of BD patients and controls.
See this image and copyright information in PMC

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