The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
Stat3 Activation Is Responsible for IL-6-Dependent T Cell Proliferation Through Preventing Apoptosis: Generation and Characterization of T Cell-Specific Stat3-Deficient Mice
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Increased apoptosis and impaired Th17 development”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Takeda et al., 1998b
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Specific disruption of STAT3 in T cells revealed that STAT3 activation is responsible for IL-6-dependent T cell proliferation through preventing apoptosis (13”
From STAT3 Contributes to the Mitogenic Response of Hepatocytes during Liver Regeneration (2002) · cites this paper as [13]
The cited source says what the claim attributes to it.
In the citing paper
“T lymphocyte lineage-specific STAT3-KO mice studies revealed the crucial role of IL-6/STAT3-mediated T cell survival, independent of Bcl-2”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Takeda et al., 1998
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Darnell, J. E. (1997) · Science · doi:10.1126/science.277.5332.1630 · Cited by 3,979
bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death
Boise, L., González‐García, M., Postema, C. E., Ding, L., Lindsten, T., Turka, L. A., Mao, X., Núñez, G., & Thompson, C. B. (1993) · Cell · doi:10.1016/0092-8674(93)90508-n · Cited by 3,089
Zhong, Z., Wen, Z., & Darnell, J. E. (1994) · Science · doi:10.1126/science.8140422 · Cited by 2,070
TRANSCRIPTIONAL RESPONSES TO POLYPEPTIDE LIGANDS: The JAK-STAT Pathway
Schindler, C., & Darnell, J. E. (1995) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.64.070195.003201 · Cited by 1,808
Impaired immune and acute-phase responses in interleukin-6-deficient mice
Kopf, M., Baumann, H., Freer, G., Freudenberg, M., Lamers, M., Kishimoto, T., Zinkernagel, R., Bluethmann, H., & Köhler, G. (1994) · Nature · doi:10.1038/368339a0 · Cited by 1,768
Self-citationMeraz, M. A., White, J. M., Sheehan, K. C. F., Bach, E. A., Rodig, S. J., Dighe, A. S., Kaplan, D. H., Riley, J. K., Greenlund, A. C., Campbell, D., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)81288-x · Cited by 1,656
Novack, D. V., Sorenson, C. M., Shutter, J. R., & Korsmeyer, S. J. (1993) · Cell · doi:10.1016/0092-8674(93)80065-m · Cited by 1,637
Stat6 Is Required for Mediating Responses to IL-4 and for the Development of Th2 Cells
Kaplan, M. H., Schindler, U., Smiley, S. T., & Grusby, M. J. (1996) · Immunity · doi:10.1016/s1074-7613(00)80439-2 · Cited by 1,629
Essential role of Stat6 in IL-4 signalling
Takeda, K., Tanaka, T., Shi, W., Matsumoto, M., Minami, M., Kashiwamura, S.-I., Nakanishi, K., Yoshida, N., Kishimoto, T., & Akira, S. (1996) · Nature · doi:10.1038/380627a0 · Cited by 1,557
Self-citationTargeted Disruption of the Mouse Stat1 Gene Results in Compromised Innate Immunity to Viral Disease
Durbin, J. E., Hackenmiller, R., Simon, M. C., & Levy, D. E. (1996) · Cell · doi:10.1016/s0092-8674(00)81289-1 · Cited by 1,539
Deletion of a DNA Polymerase β Gene Segment in T Cells Using Cell Type-Specific Gene Targeting
Gu, H., Marth, J. D., Orban, P. C., Mossmann, H., & Rajewsky, K. (1994) · Science · doi:10.1126/science.8016642 · Cited by 1,397
STATs: Signal Transducers and Activators of Transcription
Ihle, J. N. (1996) · Cell · doi:10.1016/s0092-8674(00)81277-5 · Cited by 1,381
Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality
Takeda, K., Noguchi, K., Shi, W., Tanaka, T., Matsumoto, M., Yoshida, N., Kishimoto, T., & Akira, S. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.8.3801 · Cited by 1,323
Self-citationLack of IL-4-induced Th2 response and IgE class switching in mice with disrupted Stat6 gene
Shimoda, K., van Deursent, J., Sangster, M. Y., Sarawar, S. R., Carson, R. T., Tripp, R. A., Chu, C., Quelle, F. W., Nosaka, T., Vignali, D. A. A., et al. (1996) · Nature · doi:10.1038/380630a0 · Cited by 1,278
Impaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient mice
Kaplan, M. H., Sun, Y.-L., Hoey, T., & Grusby, M. J. (1996) · Nature · doi:10.1038/382174a0 · Cited by 1,240
Requirement for Stat4 in interleukin-12-mediated responses of natural killer and T cells
Thierfelder, W. E., van Deursen, J. M., Yamamoto, K., Tripp, R. A., Sarawar, S. R., Carson, R. T., Sangster, M. Y., Vignali, D. A. A., Doherty, P. C., Grosveld, G. C., et al. (1996) · Nature · doi:10.1038/382171a0 · Cited by 1,183
Massive Cell Death of Immature Hematopoietic Cells and Neurons in Bcl-x-Deficient Mice
Motoyama, N., Wang, F., Roth, K. A., Sawa, H., Nakayama, K., Nakayama, K., Negishi, I., Senju, S., Zhang, Q., Fujii, S., et al. (1995) · Science · doi:10.1126/science.7878471 · Cited by 1,164
Stat5a is mandatory for adult mammary gland development and lactogenesis.
Liu, X., Robinson, G. W., Wagner, K. U., Garrett, L., Wynshaw-Boris, A., & Hennighausen, L. (1997) · Genes & Development · doi:10.1101/gad.11.2.179 · Cited by 1,111
Akira, S., Nishio, Y., Inoue, M., Wang, X.-J., We, S., Matsusaka, T., Yoshida, K., Sudo, T., Naruto, M., & Kishimoto, T. (1994) · Cell · doi:10.1016/0092-8674(94)90235-6 · Cited by 1,019
Self-citationRequirement of STAT5b for sexual dimorphism of body growth rates and liver gene expression
Udy, G. B., Towers, R. P., Snell, R. G., Wilkins, R. J., Park, S.-H., Ram, P. A., Waxman, D. J., & Davey, H. W. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.14.7239 · Cited by 991
Gu, H., Zou, Y.-R., & Rajewsky, K. (1993) · Cell · doi:10.1016/0092-8674(93)90644-6 · Cited by 989
Enhanced DNA-Binding Activity of a Stat3-Related Protein in Cells Transformed by the Src Oncoprotein
Yu, C.-L., Meyer, D. J., Campbell, G. S., Larner, A. C., Carter-Su, C., Schwartz, J., & Jove, R. (1995) · Science · doi:10.1126/science.7541555 · Cited by 931
Takayama, S., Sato, T., Krajewski, S., Kochel, K., Irie, S., Milian, J. A., & Reed, J. C. (1995) · Cell · doi:10.1016/0092-8674(95)90410-7 · Cited by 857
Chin, Y. E., Kitagawa, M., Su, W., You, Z.-H., Iwamoto, Y., & Fu, X.-Y. (1996) · Science · doi:10.1126/science.272.5262.719 · Cited by 816
Bcl-2 Rescues T Lymphopoiesis in Interleukin-7 Receptor–Deficient Mice
Akashi, K., Kondo, M., von Freeden-Jeffry, U., Murray, R., & Weissman, I. L. (1997) · Cell · doi:10.1016/s0092-8674(00)80291-3 · Cited by 592
Constitutively activated Jak-STAT pathway in T cells transformed with HTLV-I
Migone, T.-S., Lin, J.-X., Cereseto, A., Mulloy, J. C., O'Shea, J. J., Franchini, G., & Leonard, W. J. (1995) · Science · doi:10.1126/science.7604283 · Cited by 557
B cell stimulating factor 2/interleukin 6 is a costimulant for human thymocytes and T lymphocytes.
Lotz, M., Jirik, F. R., Kabouridis, P. S., Tsoukas, C. D., Hirano, T., Kishimoto, T., & Carson, D. A. (1988) · The Journal of Experimental Medicine · doi:10.1084/jem.167.3.1253 · Cited by 523
Self-citationRajewsky, K., Gu, H., Kühn, R., Betz, U. A. K., Müller, W., Roes, J., & Schwenk, F. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118828 · Cited by 461
Mui, A., Wakao, H., Kinoshita, T., Kitamura, T., & Miyajima, A. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00600.x · Cited by 397
Nakayama, K., Nakayama, K., Negishi, I., Kuida, K., Sawa, H., & Loh, D. Y. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.9.3700 · Cited by 395
Disappearance of the Lymphoid System in Bcl-2 Homozygous Mutant Chimeric Mice
Nakayama, K., Nakayama, K., Negishi, I., Kuida, K., Shinkai, Y., Louie, M. C., Fields, L. E., Lucas, P. J., Stewart, V., Alt, F. W., et al. (1993) · Science · doi:10.1126/science.8372353 · Cited by 394
Jaks, STATs, Cytokine Signal Transduction, and Immunoregulation: Are We There Yet?
O’Shea, J. J. (1997) · Immunity · doi:10.1016/s1074-7613(00)80505-1 · Cited by 377
Minami, M., Inoue, M., Wei, S., Takeda, K., Matsumoto, M., Kishimoto, T., & Akira, S. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.9.3963 · Cited by 335
Self-citationQuelle, F. W., Shimoda, K., Thierfelder, W. E., Fischer, C. D., Kim, A. C., Ruben, S. M., Cleveland, J. L., Pierce, J. H., Keegan, A. D., Nelms, K. A., et al. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.6.3336 · Cited by 327
IL-6 rescues resting mouse T cells from apoptosis.
Teague, T., Marrack, P., Kappler, J., & Vella, A. (1997) · Journal of Immunology · doi:10.4049/jimmunol.158.12.5791 · Cited by 280
Damen, J. E., Wakao, H., Miyajima, A., Krošl, J., Humphries, R. K., Cutler, R. L., & Krystal, G. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb00243.x · Cited by 275
Nakajima, H., Liu, X.-W., Wynshaw-Boris, A. J., Rosenthal, L. A., Imada, K., Finbloom, D. S., Hennighausen, L. G., & Leonard, W. J. (1997) · Immunity · doi:10.1016/s1074-7613(00)80389-1 · Cited by 271
Takemoto, S., Mulloy, J. C., Cereseto, A., Migone, T.-S., Patel, B. K. R., Matsuoka, M., Yamaguchi, K., Takatsuki, K., Kamihira, S., White, J. D., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.25.13897 · Cited by 271
Bernad, A., Kopf, M., Kulbacki, R., Weich, N., Koehler, G., & Gutiérrez-Ramos, J. (1994) · Immunity · doi:10.1016/s1074-7613(94)80014-6 · Cited by 242
IL-6-regulated transcription factors
Akira, S. (1997) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(97)00063-0 · Cited by 231
Self-citationLeukemia Inhibitory Factor–dependent Transcriptional Activation in Embryonic Stem Cells
Bœuf, H., Hauss, C., Graeve, F. D., Baran, N., & Kédinger, C. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.138.6.1207 · Cited by 231
Zhang, Q., Nowak, I. A., Vonderheid, E. C., Rook, A. H., Kadin, M. E., Nowell̀, P. C., Shaw, L. M. J., & Wasik, M. A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.17.9148 · Cited by 221
Nielsen, M., Kaltoft, K., Nordahl, M., Röpke, C., Geisler, C., Mustelin, T., Dobson, P., Svejgaard, A., & Ødum, N. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.13.6764 · Cited by 220
Gobert, S., Chrétien, S., Gouilleux, F., Muller, O., Pallard, C., Dusanter‐Fourt, I., Groner, B., Lacombe, C., Gisselbrecht, S., & Mayeux, P. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00601.x · Cited by 194
The Roles of γ1 Heavy Chain Membrane Expression and Cytoplasmic Tail in IgG1 Responses
Kaisho, T., Schwenk, F., & Rajewsky, K. (1997) · Science · doi:10.1126/science.276.5311.412 · Cited by 140
Self-citationbcl-2 proto-oncogene expression during human T cell development. Evidence for biphasic regulation.
Gratiot-Deans, J., Ding, L., Turka, L. A., & Núñez, G. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.151.1.83 · Cited by 135
Stat Proteins Control Lymphocyte Proliferation by Regulating p27Kip1 Expression
Kaplan, M. H., Daniel, C., Schindler, U., & Grusby, M. J. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.4.1996 · Cited by 123
Gratiot-Deans, J., Merino, R., Núñez, G., & Turka, L. A. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.22.10685 · Cited by 108
Yu, C., Jove, R., & Burakoff, S. J. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.159.11.5206 · Cited by 105
Chaturvedi, P., Sharma, S., & Reddy, E. P. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.6.3295 · Cited by 104
Wang, X.-J., Taga, T., Yoshida, K., Saito, M., Kishimoto, T., & Kikutani, H. (1998) · Blood · doi:10.1182/blood.v91.9.3308 · Cited by 38
Self-citationThe TNF receptor family member CD27 signals to Jun N-terminal kinase via Traf-2
Eugster (1998) · Pure Amsterdam UMC · doi:10.1002/(sici)1521-4141(199807)28:07 · Cited by 2
Self-citation
Flagged first, then by citations
Research works printed but not linked: 51
- 1995, Annu. Rev. Biochem., 621
- 1997, Science, 1630
- 1996, Cell, 331
- 1997, Immunity, 1
- 1996, Cell, 443
- 1996, Cell, 431
- 1996, Nature, 630
- 1996, Nature, 627
- 1996, Immunity, 313
- 1996, Nature, 174
- 1996, Nature, 171
- 1997, Genes Dev., 179
- 1997, Proc. Natl. Acad. Sci. USA, 7239
- 1995, Mol. Cell. Biol., 3336
- 1995, EMBO J., 5557
- 1996, EMBO J., 2434
- 1996, EMBO J., 2425
- 1997, Immunity, 691
- 1996, Science, 719
- 1998, Mol. Cell. Biol., 1996
- 1995, Science, 81
- 1997, Mol. Cell. Biol., 3295
- 1994, Cell, 63
- 1994, Science, 95
- 1998, Int. J. Biochem. Cell Biol., 1401
- 1995, Science, 79
- 1996, Proc. Natl. Acad. Sci. USA, 9148
- 1997, Proc. Natl. Acad. Sci. USA, 6764
- 1997, Proc. Natl. Acad. Sci. USA, 13897
- 1997, J. Immunol., 5206
- 1997, Proc. Natl. Acad. Sci. USA, 3801
- 1993, Cell, 1155
- 1994, Science, 103
- 1996, J. Clin. Invest., 600
- 1997, Science, 412
- 1998, Blood, 3308
- 1996, Proc. Natl. Acad. Sci. USA, 3963
- 1997, J. Cell Biol., 1207
- 1994, Proc. Natl. Acad. Sci. USA, 3700
- 1993, Cell, 597
- 1995, Science, 1506
- 1995, Cell, 279
- 1994, Immunity, 725
- 1994, Nature, 339
- 1988, J. Exp. Med., 1253
- 1997, J. Immunol., 5791
- 1993, J. Immunol., 83
- 1994, Proc. Natl. Acad. Sci. USA, 10685
- 1993, Science, 1584
- 1993, Cell, 229
- 1997, Cell, 1033
Cited by
Sorted by citations
Interferon-γ: an overview of signals, mechanisms and functions
Schroder, K., Hertzog, P. J., Ravasi, T., & Hume, D. A. (2004) · Journal of Leukocyte Biology · doi:10.1189/jlb.0603252 · Cited by 4,120
STATs: transcriptional control and biological impact
Levy, D. E., & Darnell, J. E. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm909 · Cited by 3,201
Bromberg, J. F., Wrzeszczynska, M. H., Devgan, G., Zhao, Y., Pestell, R. G., Albanese, C., & Darnell, J. E. (1999) · Cell · doi:10.1016/s0092-8674(00)81959-5 · Cited by 2,790
Cytokines and chemokines: At the crossroads of cell signalling and inflammatory disease
Turner, M. D., Nedjai, B., Hurst, T. P., & Pennington, D. J. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2014.05.014 · Cited by 2,289
Astrocyte scar formation aids central nervous system axon regeneration
Anderson, M. A., Burda, J. E., Ren, Y., Ao, Y., O’Shea, T. M., Kawaguchi, R., Coppola, G., Khakh, B. S., Deming, T. J., & Sofroniew, M. V. (2016) · Nature · doi:10.1038/nature17623 · Cited by 1,851
Metadata
- Authors
- Takeda, K., Kaisho, T., Yoshida, N., Takeda, J., Kishimoto, T., & Akira, S.
- Affiliations
- Hyogo Medical University (JP)
- Research Institute, Osaka Maternal and Child Health Center , Izumi, Osaka ,
- The University of Osaka (JP)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1998-11-01
- Volume
- 161
- Issue
- 9
- Pages
- 4652-4660
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W4313347835
- Cited by
- 584
- References
- 52
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 13 · 2023: 11 · 2022: 14 · 2021: 19 · 2020: 19 · 2019: 19 · 2018: 21 · 2017: 20 · 2016: 34 · 2015: 28 · 2014: 27 · 2013: 34 · 2012: 25
- FWCI
- 10.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- STAT3, interleukin-6, T cell proliferation, apoptosis, Bcl-2, conditional gene targeting, Cre-loxP system, STAT family, cell cycle progression, anti-apoptotic signaling
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review