PMID:12244150

Citation	Strengell, M, Sareneva, T, Foster, D, Julkunen, I and Matikainen, S (2002) IL-21 up-regulates the expression of genes associated with innate immunity and Th1 response. J. Immunol. 169:3600-5
Abstract	IL-21 is a recently characterized T cell-derived cytokine that regulates NK and T cell function. IL-21R shares the common gamma-chain (gamma(c)) with the receptors for IL-2, IL-4, IL-7, IL-9, and IL-15. Despite the same gamma(c), these cytokines have different effects on diverse cells. In this study, we have studied IL-15- and IL-21-induced gene expression in human primary NK and T cells and the NK-92 cell line. Both IL-15 and IL-21 rapidly induced mRNA synthesis for IFN-gamma, T-bet, IL-2Ralpha, IL-12Rbeta2, IL-18R, and myeloid differentiation factor 88 (MyD88), the genes that are important in activating innate immunity and Th1 response. IL-15 induced STAT5 DNA binding to the IL-2Ralpha IFN-gamma-activated sequence (GAS), MyD88 GAS, and c-cis-inducible elements, whereas IL-21 induced STAT3 DNA binding to MyD88 GAS and c-sis-inducible elements. IL-21-induced STAT3 activation was verified by immunoprecipitation and Western blotting with anti-phosphotyrosine Ab. In addition, pretreatment of NK-92 cells with IL-15 or IL-21 strongly enhanced IL-12-induced STAT4 DNA binding to IL-2Ralpha GAS. The induction of IFN-gamma, T-bet, IL-12Rbeta2, and IL-18R gene expression in NK cells, along with STAT3 activation, suggests that IL-21 is involved in the activation of innate immune responses. Moreover, the enhanced transcription of these genes in T cells establishes a significant role for IL-21 also in the Th1 response.
Links	PubMed
Keywords	Adaptor Proteins, Signal Transducing; Antigens, Differentiation/metabolism; Cells, Cultured; DNA-Binding Proteins/metabolism; Gene Expression Regulation/immunology; Humans; Immunity, Innate/genetics; Interferon Regulatory Factor-1; Interleukin-15/pharmacology; Interleukins/pharmacology; Interleukins/physiology; Janus Kinase 1; Janus Kinase 3; Killer Cells, Natural/metabolism; Lymphocyte Activation/genetics; Lymphocyte Activation/immunology; Milk Proteins; Myeloid Differentiation Factor 88; Phosphoproteins/metabolism; Phosphorylation; Protein Binding/immunology; Protein-Tyrosine Kinases/metabolism; Receptors, Immunologic/metabolism; Response Elements/immunology; STAT1 Transcription Factor; STAT3 Transcription Factor; STAT5 Transcription Factor; T-Box Domain Proteins; T-Lymphocyte Subsets/immunology; T-Lymphocyte Subsets/metabolism; Th1 Cells/immunology; Th1 Cells/metabolism; Trans-Activators/metabolism; Transcription Factors/metabolism; Tyrosine/metabolism; Up-Regulation/genetics; Up-Regulation/immunology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:IL21		GO:0042503: tyrosine phosphorylation of Stat3 protein	ECO:0000314:		P		Fig. 6 shows that IL-21 induces tyrosine phosphorylation of Stat3.	complete CACAO 5719
HUMAN:IL21		GO:0042517: positive regulation of tyrosine phosphorylation of Stat3 protein	ECO:0000314:		P		Figure 6 shows that when stimulated with IL21, STAT3 becomes more phosphorylated on tyrosine residues, but STAT5 does not.	complete CACAO 5753
HUMAN:IL21		GO:0010537: positive regulation of activation of JAK1 kinase activity	ECO:0000314:		P		Figure 7 shows stimulation with IL21 increases JAK1 tyrosine phosphorylation.	complete CACAO 5754
HUMAN:IL21	involved_in	GO:0007260: tyrosine phosphorylation of STAT protein	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:IL15		GO:0042506: tyrosine phosphorylation of Stat5 protein	ECO:0000314:		P		Fig. 6 shows induction of tyrosine phosphorylation by IL-15.	complete CACAO 5774
HUMAN:IL15	involved_in	GO:0007260: tyrosine phosphorylation of STAT protein	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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