Stat3 activation is responsible for IL-6-dependent T cell proliferation through preventing apoptosis: generation and characterization of T cell-specific Stat3-deficient mice.
Stat3, a member of STAT, is activated by a variety of cytokines such as IL-6 family of cytokines, granulocyte CSF, epidermal growth factor, and leptin. A recent study with mice genetically deficient in the Stat3 gene has revealed its important role in the early embryogenesis. To assess the function of Stat3 in adult tissues, we disrupted the Stat3 gene specifically in T cells by conditional gene targeting using Cre-loxP system. In Stat3-deficient T cells, IL-6-induced proliferation was severely impaired. IL-6 did not enhance cell cycle progression, but prevented apoptosis of normal T cells. In contrast, IL-6 did not prevent apoptosis of Stat3-deficient T cells. Antiapoptotic protein, Bcl-2, was normally up-regulated in response to IL-6 even in Stat3-deficient T cells. These results demonstrate that Stat3 activation is involved in IL-6-dependent T cell proliferation through prevention of apoptosis independently of Bcl-2.
Takeda
K
K
Department of Biochemistry, Hyogo College of Medicine, Nishinomiya, Japan.
Kaisho
T
T
Yoshida
N
N
Takeda
J
J
Kishimoto
T
T
Akira
S
S
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001483:Base Sequence; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D019254:Genes, bcl-2; D019426:Integrases / Q000235:genetics / Q000502:physiology; D015850:Interleukin-6 / Q000494:pharmacology / Q000502:physiology*; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000502:physiology; D050796:STAT3 Transcription Factor; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014764:Viral Proteins
D016207:Cytokines; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D014764:Viral Proteins; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); C045073:Cre recombinase; D019426:Integrases