Human Gene Set: MARZEC_IL2_SIGNALING_DN


Standard name MARZEC_IL2_SIGNALING_DN
Systematic name M13276
Brief description Genes down-regulated by IL2 [GeneID=3558] in cells derived from CD4+ [GeneID=920] cutaneous T-cell lymphoma (CTCL).
Full description or abstract In this study, we compared the effects of interleukin-2 (IL-2), IL-15, and IL-21 on gene expression, activation of cell signaling pathways, and functional properties of cells derived from CD4+ cutaneous T-cell lymphoma (CTCL). Whereas both IL-2 and IL-15 modulated, in a CTCL cell line, the expression of >1,000 gene transcripts by at least 2-fold, IL-21 up-regulated <40 genes. All three cytokines induced tyrosine phosphorylation of Jak1 and Jak3 in CTCL cell lines and native leukemic (Sezary) cells. However, only IL-2 and IL-15 strongly activated signal transducers and activators of transcription 5, phosphoinositide 3-kinase/Akt, and mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase/ERK signaling pathways in the cell lines and mitogen-primed native cells. In contrast, IL-21 selectively activated signal transducers and activators of transcription 3. Whereas all three cytokines protected CTCL cells from apoptosis, only IL-2 and IL-15 promoted their proliferation. The effects of the cytokine stimulation were Jak3 kinase- and Jak1 kinase- dependent. These findings document the vastly different effect of IL-2 and IL-15 versus IL-21 on CTCL cells. They also suggest two novel therapeutic approaches to CTCL and, possibly, other CD4+ T-cell lymphomas: inhibition of the Jak1/Jak3 kinase complex and, given the known strong immunostimulatory properties of IL-21 on CD8+ T, natural killer, and B cells, application of this cytokine to boost an immune response against malignant CD4+ T cells.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 18281483   Authors: Marzec M,Halasa K,Kasprzycka M,Wysocka M,Liu X,Tobias JW,Baldwin D,Zhang Q,Odum N,Rook AH,Wasik MA
Exact source Table 1: Down-regulated
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Version history 3.0: First introduced

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