Abstract
We performed a network-based analysis of DNA microarray data from allergen-challenged CD4+ T cells from patients with seasonal allergic rhinitis. Differentially expressed genes were organized into a functionally annotated network using the Ingenuity Knowledge Database, which is based on manual review of more than 200 000 publications. The main function of this network is the regulation of lymphocyte apoptosis, a role associated with several genes of the tuber necrosis factor superfamily. The expression of TNFRSF4, one of the genes in this family, was found to be 48 times higher in allergen-challenged cells than in diluent-challenged cells. TNFRSF4 is known to inhibit apoptosis and to enhance Th2 proliferation. Examination of a different material of allergen-stimulated peripheral blood mononuclear cells showed a higher number of interleukin-4+ type 2 CD4+ T (Th2) cells in patients than in controls (P<0.01), as well as a higher number of non-apoptotic Th2 cells in patients (P<0.01). The number of Th2 cells expressing TNFRSF4, TNFSF7 and TNFRSF1B was also significantly higher in patients. Treatment with anti-TNFSF4 resulted in a significantly decreased number of Th2 cells (P<0.05). A logical inference from all this is that the proliferation of allergen-challenged Th2 cells is associated with a decreased apoptosis of Th2 cells and an increase in TNFRSF4 signalling.
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Acknowledgements
We thank Jörgen Nedergaard-Larsen of ALK for kindly providing allergen extract and advice concerning the extract. This study was supported by grants from the US National Institutes of Health, the Swedish Medical Research Council, the, Sahlgrenska Academy and the Swedish Asthma and Allergy Foundation.
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Benson, M., Carlsson, L., Guillot, G. et al. A network-based analysis of allergen-challenged CD4+ T cells from patients with allergic rhinitis. Genes Immun 7, 514–521 (2006). https://doi.org/10.1038/sj.gene.6364322
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DOI: https://doi.org/10.1038/sj.gene.6364322
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