Ly-6A/E induction by interleukin-6 and interleukin-9 in T cells.
Interleukin-6 (IL-6) is active in the early steps of T cell activation and confers IL-2 responsiveness. In this work, we used EL4 T lymphoma to identify IL-6 target genes in T cells. By differential screening of a cDNA library, we found that IL-6 induced the expression of Ly-6A/E, a GPI-anchored cell surface protein reported to be a regulator of T cell activation. In addition to IL-6, IL-9 and IFN-gamma induced Ly-6A/E expression in EL4 and BW5147 cells. We showed that both IL-6 and IL-9 mediated the transcriptional activation of Ly-6A/E through a GAS element in the Ly-6A/E promoter, which was able to bind STAT1 and STAT3, transcription factors activated by these cytokines. IL-6 had a similar effect in freshly isolated normal T cells, and dramatically increased their proliferation upon Ly-6A/E stimulation. Taken together, our data suggest that Ly-6A/E induction takes part in the T cell activation program initiated by IL-6.
Demoulin
J B
JB
Ludwig Institute for Cancer Research, avenue Hippocrate, 74, B-1200 Brussels, Belgium.
Maisin
D
D
Renauld
J C
JC
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D016906:Interleukin-9 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D016399:Lymphoma, T-Cell / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008811:Mice, Inbred DBA; D010693:Phloretin / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D018123:Receptors, Interleukin / Q000235:genetics / Q000502:physiology*; D053651:Receptors, Interleukin-9; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D000950:Antigens, Ly; C508045:IL9R protein, human; D015850:Interleukin-6; D016906:Interleukin-9; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D018123:Receptors, Interleukin; D053651:Receptors, Interleukin-9; D011994:Recombinant Proteins; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D010693:Phloretin