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

Tulunay, A. et al. (2015) Activation of the JAK/STAT pathway in Behcet's disease. Genes and Immunity, 16(2), pp. 170-175. (doi: 10.1038/gene.2014.64) (PMID:25410656) (PMCID:PMC4443896)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Tulunay Virlan, Dr Aysin
Authors: Tulunay, A., Dozmorov, M. G., Ture-Ozdemir, F., Yilmaz, V., Eksioglu-Demiralp, E., Alibaz-Oner, F., Ozen, G., Wren, J. D., Saruhan-Direskeneli, G., Sawalha, A. H., and Direskeneli, H.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Genes and Immunity
Publisher:Springer Nature
ISSN:1466-4879
ISSN (Online):1476-5470
Published Online:20 November 2014

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