A point mutation of Tyr-759 in interleukin 6 family cytokine receptor subunit gp130 causes autoimmune arthritis
Open accessAbstract
We generated a mouse line in which the src homology 2 domain–bearing protein tyrosine phosphatase (SHP)-2 binding site of gp130, tyrosine 759, was mutated to phenylalanine (gp130F759/F759). The gp130F759/F759 mice developed rheumatoid arthritis (RA)-like joint disease. The disease was accompanied by autoantibody production and accumulated memory/activated T cells and myeloid cells. Before the disease onset, the T cells were hyperresponsive and thymic selection and peripheral clonal deletion were impaired. The inhibitory effect of IL-6 on Fas ligand expression during activation-induced cell death (AICD) was augmented in gp130F759/F759 T cells in a manner dependent on the tyrosine residues of gp130 required for signal transducer and activator of transcription 3 activation. Finally, we showed that disease development was dependent on lymphocytes. These results provide evidence that a point mutation of a cytokine receptor has the potential to induce autoimmune disease.
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Enhancement of IL-6-STAT3 signaling causes IL-17A-dependent autoimmune arthritis in mice.
“On the other hand, the enhancement of IL-6–STAT3 signaling causes IL-17A-dependent autoimmune arthritis in mice (41, 63, 66).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [63]
The Introduction reports that gp130 mutant mice have enhanced STAT3 signaling and spontaneously develop lymphocyte-dependent arthritis; the Discussion links augmented gp130-mediated STAT3 activation to autoimmune joint disease. The paper does not establish that the arthritis is IL-17A-dependent: its Discussion identifies a requirement for lymphocytes, not IL-17A (searched: IL-17A, interleukin 17, Th17). (LLM, conf=0.89)
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Hirano, T., Yasukawa, K., Harada, H., Taga, T., Watanabe, Y., Matsuda, T., Kashiwamura, S.-I., Nakajima, K., Koyama, K., Iwamatsu, A., et al. (1986) · Nature · doi:10.1038/324073a0 · Cited by 2,139 · cited 1× · see citing works
“IL-6, which was originally identified as a B cell differentiation factor (13, 14), is now known to be a multifunctional cytokine that regulates the immune response, hematopoiesis, the acute phase response, and inflammation (4, 15).”
BackgroundSelf-citationVan Snick, J. (1990) · Annual Review of Immunology · doi:10.1146/annurev.iy.08.040190.001345 · Cited by 1,890 · cited 1× · see citing works
“IL-6, which was originally identified as a B cell differentiation factor (13, 14), is now known to be a multifunctional cytokine that regulates the immune response, hematopoiesis, the acute phase response, and inflammation (4, 15).”
BackgroundTolerance in T-cell-receptor transgenic mice involves deletion of nonmature CD4+8+ thymocytes
Kisielow, P., Blüthmann, H., Staerz, U., Steinmetz, M., & von Boehmer, H. (1988) · Nature · doi:10.1038/333742a0 · Cited by 1,793 · cited 1× · see citing works
“We crossed gp130F759/F759 mice with anti–HY-TCR transgenic mice to examine the effect of the gp130F759/F759 mutation on thymic selection (39).”
MethodTransgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis.
Keffer, J., Probert, L., Cazlaris, H., Georgopoulos, S., Kaslaris, E., Kioussis, D., & Kollias, G. (1991) · EMBO Journal · doi:10.1002/j.1460-2075.1991.tb04978.x · Cited by 1,675 · cited 1× · see citing works
“TNF- transgenic mice and TNF AU-rich elements-deficient mice revealed that TNF- is a pivotal cytokine for the induction of other proinflammatory cytokines and for the abnormal growth of synovial cells (9, 10).”
BackgroundImpaired On/Off Regulation of TNF Biosynthesis in Mice Lacking TNF AU-Rich Elements
Kontoyiannis, D. L., Pasparakis, M., Pizarro, T. T., Cominelli, F., & Kollias, G. A. (1999) · Immunity · doi:10.1016/s1074-7613(00)80038-2 · Cited by 1,329 · cited 2× · see citing works
“This is in sharp contrast to the arthritis that develops in TNF AUrich elements-deficient mice, which is independent of lymphocytes (9).”
BackgroundResultHirano, T., Ishihara, K., & Hibi, M. (2000) · Oncogene · doi:10.1038/sj.onc.1203551 · Cited by 1,276 · see citing works
Self-citationHomeostasis and Self-Tolerance in the Immune System: Turning Lymphocytes off
Parijs, L. V., & Abbas, A. K. (1998) · Science · doi:10.1126/science.280.5361.243 · Cited by 958 · see citing works
Organ-specific disease provoked by systemic autoimmunity.
Kouskoff, V., Korganow, A., Duchatelle, V., Degott, C., Benoist, C., & Mathis, D. (1996) · Cell · doi:10.1016/s0092-8674(00)81989-3 · Cited by 949 · cited 1× · see citing works
“Analyses of the K/BxN TCR transgenic mouse showed that an autoantibody specific to a ubiquitous molecule can induce an organ-specific autoimmune disease (2, 6, 7).”
BackgroundHorai, R., Saijo, S., Tanioka, H., Nakae, S., Sudo, K., Okahara, A., Ikuse, T., Asano, M., & Iwakura, Y. (2000) · Journal of Experimental Medicine · doi:10.1084/jem.191.2.313 · Cited by 792 · cited 1× · see citing works
“IL-1 transgenic mice (11) and gene targeting of an IL-1 receptor antagonist (12) indicated that the increased T.”
BackgroundInterleukin 6 and its receptor: ten years later
Hirano, T. (1998) · International Reviews of Immunology · doi:10.3109/08830189809042997 · Cited by 788 · see citing works
Self-citationExcessive production of interleukin 6/B cell stimulatory factor-2 in rheumatoid arthritis
Hirano, T., Matsuda, T., Turner, M., Miyasaka, N., Buchan, G., Tang, B., Sato, K., Shimi, M., Maid, R., Feldmann, M., et al. (1988) · European Journal of Immunology · doi:10.1002/eji.1830181122 · Cited by 784 · cited 1× · see citing works
“Since then, several pieces of evidence have been reported that suggest the involvement of IL-6 in autoimmune diseases, including RA (4, 17).”
BackgroundSelf-citationFortin, P. R., Clarke, A. E., Joseph, L., Liang, M. H., Tänzer, M., Ferland, D., Phillips, C., Partridge, A. J., B�lisle, P., Fossel, A. H., et al. (1999) · Arthritis & Rheumatism · doi:10.1002/1529-0131(199908)42:8 · Cited by 708 · see citing works
Self-citationKawabe, Y., & Ochi, A. (1991) · Nature · doi:10.1038/349245a0 · Cited by 703 · cited 1× · see citing works
“For this study we injected a superantigen, SEB, into the mice (41).”
MethodArthritis provoked by linked T and B cell recognition of a glycolytic enzyme.
Matsumoto, I., Staub, A., Benoist, C., & Mathis, D. (1999) · Science · doi:10.1126/science.286.5445.1732 · Cited by 667 · cited 2× · see citing works
“The involvement of autoantibody in RA or experimentally induced arthritis model has been recently reconsidered (2, 7).”
BackgroundFukada, T., Hibi, M., Yamanaka, Y., Takahashi-Tezuka, M., Fujitani, Y., Yamaguchi, T., Nakajima, K., & Hirano, T. (1996) · Immunity · doi:10.1016/s1074-7613(00)80501-4 · Cited by 652 · cited 1× · see citing works
“Several experiments in vitro have indicated that the SHP-2– and STAT-3–mediated signal-transduction pathways that are initiated through gp130 are involved in growth, differentiation, and gene expression in various cell lines (24, 25, 27, 28).”
BackgroundSelf-citationQuantification of murine cytokine mRNAs using real time quantitative reverse transcriptase PCR.
Overbergh, L., Valckx, D., Waer, M., & Mathieu, C. (1999) · Cytokine · doi:10.1006/cyto.1998.0426 · Cited by 623 · see citing works
Interleukin 6 is required for the development of collagen-induced arthritis
Alonzi, T., Fattori, E., Lazzaro, D., Costa, P., Probert, L., Kollias, G., De Benedetti, F., Poli, V., & Ciliberto, G. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.187.4.461 · Cited by 604 · see citing works
Takeda, K., Kaisho, T., Yoshida, N., Takeda, J., Kishimoto, T., & Akira, S. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.9.4652 · Cited by 584 · see citing works
Nakajima, K., Yamanaka, Y., Nakae, K., Kojima, H., Ichiba, M., Kiuchi, N., Kitaoka, T., Fukada, T., Hibi, M., & Hirano, T. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00734.x · Cited by 565 · cited 1× · see citing works
“Several experiments in vitro have indicated that the SHP-2– and STAT-3–mediated signal-transduction pathways that are initiated through gp130 are involved in growth, differentiation, and gene expression in various cell lines (24, 25, 27, 28).”
BackgroundSelf-citationRole of cytokines in rheumatoid arthritis.
Odeh, M. (1998) · Drug News and Perspectives · doi:10.1358/dnp.1998.11.6.661380 · Cited by 483 · cited 1×
“digits of the forelimb; (2) swelling of the footpad; (3) swelling of”
BackgroundNicholson, S. E., De Souza, D., Fabri, L. J., Corbin, J., Willson, T. A., Zhang, J.-G., Silva, A., Asimakis, M., Farley, A., Nash, A. D., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.100135197 · Cited by 456 · cited 9× · see citing works
“Transcription levels of SOCS-3 mRNA were estimated by quantitative RT-PCR.”
BackgroundInfluentialSamoilova, E. B., Horton, J. L., Hilliard, B. A., Liu, T.-S. T., & Chen, Y. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.12.6480 · Cited by 441 · cited 1× · see citing works
“Furthermore, IL-6 is required for experimentally induced autoimmune diseases or autoimmunity, including type II collagen- and antigen-induced arthritis (18– 20), myelin oligodendrocyte protein-induced experimental autoimmune encephalomyelitis (21, 22), and pristaneinduced autoantibody production (23).”
BackgroundBouneaud, C., Kourilsky, P., & Bousso, P. (2000) · Immunity · doi:10.1016/s1074-7613(00)00080-7 · Cited by 431 · cited 1× · see citing works
“It has been reported that substantially self-reactive clones with TCRs that have low avidity to self-antigen escape negative selection (43).”
BackgroundInterleukin 6 plays a key role in the development of antigen-induced arthritis
Ohshima, S., Saeki, Y., Mima, T., Sasai, M., Nishioka, K., Nomura, S., Kopf, M., Katada, Y., Tanaka, T., Suemura, M., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.14.8222 · Cited by 406 · see citing works
Self-citationSchmitz, J., Weissenbach, M., Haan, S., Heinrich, P. C., & Schaper, F. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.17.12848 · Cited by 388 · cited 9× · see citing works
“Transcription levels of SOCS-3 mRNA were estimated by quantitative RT-PCR.”
BackgroundInfluentialSignaling mechanisms through gp130: A model of the cytokine system
Hirano, T., Nakajima, K., & Hibi, M. (1997) · Cytokine & Growth Factor Reviews · doi:10.1016/s1359-6101(98)80005-1 · Cited by 370 · cited 4× · see citing works
“gp130 is shared by the receptors for IL-6 family cytokines, including leukemia inhibitory factor, ciliary neurotropic factor, oncostatin M, IL-11, and cardiotropin-1 (24).”
BackgroundInfluentialSelf-citationInduction of inflammatory arthropathy resembling rheumatoid arthritis in mice transgenic for HTLV-I
Iwakura, Y., Tosu, M., Yoshida, E., Takiguchi, M., Sato, K., Kitajima, I., Nishioka, K., Yamamoto, K., Takeda, T., Hatanaka, M., et al. (1991) · Science · doi:10.1126/science.1887217 · Cited by 359 · cited 1× · see citing works
“The HTLV-1 transgenic mouse is an animal model of arthritis that is triggered by viral infection (8).”
BackgroundHirano, T., Taga, T., Yasukawa, K., Nakajima, K., Nakano, N., Takatsuki, F., Shimizu, M., Murashima, A., Tsunasawa, S., & Sakiyama, F. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.1.228 · Cited by 351 · cited 1× · see citing works
“The first suggestion that IL-6 is involved in autoimmunity came from the finding that it is produced by cardiac myxoma cells, and patients with cardiac myxoma frequently show autoimmune symptoms (16).”
BackgroundSelf-citationOhtani, T., Ishihara, K., Atsumi, T., Nishida, K., Kaneko, Y., Miyata, T., Itoh, S., Narimatsu, M., Maeda, H., Fukada, T., et al. (2000) · Immunity · doi:10.1016/s1074-7613(00)80162-4 · Cited by 284 · cited 6× · see citing works
“7 d, the IL-6–induced tyrosine-phosphorylation of JAK-1 and STAT-3 was prolonged, compared with wild-type T cells, consistent with the previous results observed in gp130F759/F759 fibroblasts (33).”
BackgroundMethodResultInfluentialSelf-citationIL-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 · see citing works
Teh, H., Kishi, H., Scott, B., & von Boehmer, H. (1989) · Journal of Experimental Medicine · doi:10.1084/jem.169.3.795 · Cited by 249 · cited 1×
“5 b), which are thought to be the thymocytes that have escaped negative selection (40), was higher in gp130F759/F759 mice, indicating that the negative selection in gp130F759/F759 mice was impaired to some exFigure 3.”
BackgroundSengupta, T. K., Talbot, E. S., Scherle, P., & Ivashkiv, L. (1998) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.95.19.11107 · Cited by 245 · cited 1× · see citing works
“SHP-2–mediated ERK mitogen-activated protein (MAP) kinase activation has been suggested to play negative roles in STAT-3–mediated biological responses (29, 30).”
BackgroundErnst, M., Inglese, M., Waring, P., Campbell, I. K., Bao, S., Clay, F. J., Alexander, W. S., Wicks, I. P., Tarlinton, D. M., Novak, U., et al. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.194.2.189 · Cited by 227 · cited 1× · see citing works
“reported that the knock-in mouse gp130 STAT/ STAT displays impaired acute phase and immune responses and develops severe gastrointestinal ulceration and joint disease (42).”
BackgroundRepression of Stat3 activity by activation of mitogen-activated protein kinase (MAPK)
Jain, N., Zhang, T., Fong, S., Lim, C. P., & Cao, X. (1998) · Oncogene · doi:10.1038/sj.onc.1202238 · Cited by 213 · cited 1× · see citing works
“SHP-2–mediated ERK mitogen-activated protein (MAP) kinase activation has been suggested to play negative roles in STAT-3–mediated biological responses (29, 30).”
BackgroundRichards, H., Satoh, M., Shaw, M., Libert, C., Poli, V., & Reeves, W. (1998) · Journal of Experimental Medicine · doi:10.1084/jem.188.5.985 · Cited by 213 · cited 1× · see citing works
“Furthermore, IL-6 is required for experimentally induced autoimmune diseases or autoimmunity, including type II collagen- and antigen-induced arthritis (18– 20), myelin oligodendrocyte protein-induced experimental autoimmune encephalomyelitis (21, 22), and pristaneinduced autoantibody production (23).”
BackgroundNarimatsu, M., Maeda, H., Itoh, S., Atsumi, T., Ohtani, T., Nishida, K., Itoh, M., Kamimura, D., Park, S., Mizuno, K., et al. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.19.6615-6625.2001 · Cited by 145 · see citing works
Self-citationTeranishi, T., Hirano, T., Arima, N., & Onoue, K. (1982) · Journal of Immunology · doi:10.4049/jimmunol.128.4.1903 · Cited by 110 · cited 1× · see citing works
“IL-6, which was originally identified as a B cell differentiation factor (13, 14), is now known to be a multifunctional cytokine that regulates the immune response, hematopoiesis, the acute phase response, and inflammation (4, 15).”
BackgroundSelf-citationMacrophage- and neutrophil- dominant arthritis in human IL-1α transgenic mice
Niki, Y., Yamada, H., Seki, S., Kikuchi, T., Takaishi, H., Toyama, Y., Fujikawa, K., & Tada, N. (2001) · Journal of Clinical Investigation · doi:10.1172/jci11530 · Cited by 100 · cited 1× · see citing works
“IL-1 transgenic mice (11) and gene targeting of an IL-1 receptor antagonist (12) indicated that the increased T.”
BackgroundHibi, M., & Hirano, T. (2000) · Leukemia and Lymphoma · doi:10.3109/10428190009089430 · Cited by 94 · cited 1× · see citing works
“The src homology 2 domain–bearing protein tyrosine phosphatase (SHP)-2, is recruited to the phosphorylated tyrosine residue Y759 in gp130, where it becomes activated and forms a complex with the adaptor docking proteins, Gab1 and Gab2, leading to activation of the Ras–MAP kinase pathway (26).”
BackgroundSelf-citationAyroldi, E., Zollo, O., Cannarile, L., Adamio, F. D., Grohmann, U., Delfino, D., & Riccardi, C. (1998) · Blood · doi:10.1182/blood.v92.11.4212 · Cited by 87 · cited 1× · see citing works
“Several reports indicated that IL-6 has antiapoptotic effects on naive but not activated T cells (45–47), and the inhibition of AICD and downregulation of FasL by IL-6 has been reported previously (48).”
BackgroundRegulation of activation-induced cell death of mature T-lymphocyte populations
Janßen, O., Sanzenbacher, R., & Kabelitz, D. (2000) · Cell and Tissue Research · doi:10.1007/s004419900155 · Cited by 82 · cited 1× · see citing works
“In addition to thymic selection, the clonal deletion of activated T cells in the periphery is important to maintain selftolerance (37, 44).”
BackgroundItoh, M., Ishihara, K., Hiroi, T., Lee, B. O., Maeda, H., Iijima, H., Yanagita, M., Kiyono, H., & Hirano, T. (1998) · Journal of Immunology · doi:10.4049/jimmunol.161.8.3974 · Cited by 71 · cited 1× · see citing works
“Serum levels of total Igs were determined by an isotype-specific ELISA as described previously (34).”
MethodSelf-citationDelayed onset and reduced severity of collagen-induced arthritis in interleukin-6-deficient mice
梅下, 光. (2000) · doi:10.11501/3169227 · Cited by 55
Ishihara, K., Kobune, Y., Okuyama, Y., Itoh, M., Lee, B. O., Muraoka, O., & Hirano, T. (1996) · International Immunology · doi:10.1093/intimm/8.9.1395 · Cited by 34 · cited 1× · see citing works
“Flow cytometry analysis was performed as described previously (36), and analyzed using a FACSCaliburTM flow cytometer (Becton Dickinson).”
MethodSelf-citationRevival of the autoantibody model in rheumatoid arthritis
Hirano, T. (2002) · Nature Immunology · doi:10.1038/ni0402-342 · Cited by 29 · cited 4× · see citing works
“digits of the forelimb; (2) swelling of the footpad; (3) swelling of”
BackgroundInfluentialSelf-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 · see citing works
Flagged first, then by citations
3 of the 49 references couldn’t be matched to a known paper.
Research works printed but not linked: 4
- [1]Feldmann, M., F.M. Brennan, and R.N. Maini. 1996. Rheumatoid arthritis. Cell. 85: 307–310. 8616886
- [5]O'Shea, J.J., A. Ma, and P. Lipsky. 2002. Cytokines and autoimmunity. Nat. Rev. Immunol. 2: 37–45. 11905836
- [22]Eugster, H.P., K. Frei, M. Kopf, H. Lassmann, and A. Fontana. 1998. IL-6-deficient mice resist myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis. Eur. J. Immunol. 28: 2178–2187. 9692887
- [38]Kamradt, T., and N.A. Mitchison. 2001. Tolerance and autoimmunity. N. Engl. J. Med. 344: 655–664. 11228281
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Revisiting STAT3 signalling in cancer: new and unexpected biological functions
Yu, H., Lee, H., Herrmann, A., Buettner, R., & Jove, R. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3818 · Cited by 2,137 · see citing works
IL-6 in inflammation, autoimmunity and cancer
Hirano, T. (2021) · International Immunology · doi:10.1093/intimm/dxaa078 · Cited by 1,453 · see citing works
“Similarly, defective STAT3 activation enhances SHP-2–ERK–MAPK activation pathways, most likely through an impaired STAT3-mediated induction of suppressor of cytokine signaling 3 (SOCS3) (111, 112).”
BackgroundInfluentialSelf-citationRecent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer
Jones, S. A., & Jenkins, B. J. (2018) · Nature Reviews Immunology · doi:10.1038/s41577-018-0066-7 · Cited by 1,102 · see citing works
Sakaguchi, N., Takahashi, T., Hata, H., Nomura, T., Tagami, T., Yamazaki, S., Sakihama, T., Matsutani, T., Negishi, I., Nakatsuru, S., et al. (2003) · Nature · doi:10.1038/nature02119 · Cited by 881 · see citing works
Directing Transition from Innate to Acquired Immunity: Defining a Role for IL-6
Jones, S. A. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.6.3463 · Cited by 771 · see citing works
“Such mechanisms for evading apoptotic cell death are also evident in vivo, with development of autoimmune arthritis in mice displaying exaggerated gp130-mediated STAT3 activity being associated with an inability of T cells to enter apoptosis (51).”
BackgroundIL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages
Yasukawa, H., Ohishi, M., Mori, H., Murakami, M., Chinen, T., Aki, D., Hanada, T., Takeda, K., Akira, S., Hoshijima, M., et al. (2003) · Nature Immunology · doi:10.1038/ni938 · Cited by 771 · see citing works
Self-citationSuppressors of cytokine signaling and immunity
Kubo, M., Hanada, T., & Yoshimura, A. (2003) · Nature Immunology · doi:10.1038/ni1012 · Cited by 614 · see citing works
Interleukin 6: from bench to bedside
Nishimoto, N., & Kishimoto, T. (2006) · Nature Clinical Practice Rheumatology · doi:10.1038/ncprheum0338 · Cited by 639 · see citing works
Ogura, H., Murakami, M., Okuyama, Y., Tsuruoka, M., Kitabayashi, C., Kanamoto, M., Nishihara, M., Iwakura, Y., & Hirano, T. (2008) · Immunity · doi:10.1016/j.immuni.2008.07.018 · Cited by 564 · see citing works
“(Atsumi et al., 2002; Ishihara et al., 2004; Sawa et al., 2006).”
BackgroundInfluentialSelf-citationKorn, T., Mitsdoerffer, M., Croxford, A. L., Awasthi, A., Dardalhon, V., Galileos, G., Vollmar, P., Stritesky, G. L., Kaplan, M. H., Waisman, A., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0809850105 · Cited by 510 · see citing works
“Interestingly, decreased gp130-triggered SHP/ERK signaling and increased gp130-triggered STAT3 signaling result in autoimmunity (13).”
BackgroundCytokine Networks in the Pathogenesis of Rheumatoid Arthritis
Kondo, N., Kuroda, T., & Kobayashi, D. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222010922 · Cited by 31 · see citing works
“F759 mice, which carry the Y759F mutation in gp130 and lack the negative feedback loop mediated by SOCS3, develop arthritis spontaneously [39].”
BackgroundPleiotropy and specificity: insights from the interleukin 6 family of cytokines
Murakami, M., Kamimura, D., & Hirano, T. (2019) · Immunity · doi:10.1016/j.immuni.2019.03.027 · Cited by 533 · see citing works
Self-citationIL-6 regulates in vivo dendritic cell differentiation through STAT3 activation
Park, S.-J., Nakagawa, T., Kitamura, H., Atsumi, T., Kamon, H., Sawa, S.-I., Kamimura, D., Ueda, N., Iwakura, Y., Ishihara, K., et al. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.6.3844 · Cited by 519 · see citing works
“This is surprising, because IL-6 has been considered to be an inflammatory cytokine and is implicated in autoimmune diseases and inflammation (33, 55, 56).”
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“sIL-6R binds to IL-6 with comparable affinity as the mbIL-6R (21); consequently, the complex of IL-6/sIL-6R can activate gp130, a membrane protein is ubiquitously expressed (22–25).”
BackgroundInterleukin-6 as a key player in systemic inflammation and joint destruction
Fonseca, J. E., Santos, M. J., Canhão, H. M., & Choy, E. (2009) · Autoimmunity Reviews · doi:10.1016/j.autrev.2009.01.012 · Cited by 374 · see citing works
IL-6 trans-signaling via STAT3 directs T cell infiltration in acute inflammation
McLoughlin, R. M., Jenkins, B. J., Grail, D., Williams, A. S., Fielding, C. A., Parker, C. R., Ernst, M., Topley, N., & Jones, S. A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501794102 · Cited by 332 · see citing works
Noss, E. H., & Brenner, M. B. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00648.x · Cited by 354 · see citing works
Mori, T., Miyamoto, T., Yoshida, H., Asakawa, M., Kawasumi, M., Kobayashi, T., Morioka, H., Chiba, K., Toyama, Y., & Yoshimura, A. (2011) · International Immunology · doi:10.1093/intimm/dxr077 · Cited by 328 · see citing works
Acquiring signalling specificity from the cytokine receptor gp130
Ernst, M. (2003) · Trends in Genetics · doi:10.1016/j.tig.2003.11.003 · Cited by 297 · see citing works
Nowell, M., Richards, P. J., Horiuchi, S., Yamamoto, N., Rose-John, S., Topley, N., Williams, A., & Jones, S. A. (2003) · Journal of Immunology · doi:10.4049/jimmunol.171.6.3202 · Cited by 293 · see citing works
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BackgroundReview: IL-6 Transsignaling: The In Vivo Consequences
Jones, S. A., Richards, P. J., Scheller, J., & Rose‐John, S. (2005) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2005.25.241 · Cited by 251 · see citing works
McLoughlin, R. M., Witowski, J., Robson, R. L., Wilkinson, T. S., Hurst, S. M., Williams, A. S., Williams, J. D., Rose-John, S., Jones, S. A., & Topley, N. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17129 · Cited by 281 · see citing works
“In more chronic conditions such as hepatitis, inflammatory bowel disease, and arthritis, however, characterized by activated T cell infiltration, the balance of STAT1 and STAT3 signaling (presumably controlled by local IL-6 and IFN-γ levels) contributes directly to disease progression (41, 42, 47).”
BackgroundIL-6 signal transduction and its physiological roles: the signal orchestration model
Kamimura, D., Ishihara, K., & Hirano, T. (2003) · Reviews of Physiology, Biochemistry and Pharmacology · doi:10.1007/s10254-003-0012-2 · Cited by 673 · see citing works
“To our knowledge, this is the first and only direct evidence that a point mutation of a cytokine receptor has the potential to induce autoimmune disease (Atsumi et al. 2002).”
BackgroundSelf-citationNishihara, M., Ogura, H., Ueda, N., Tsuruoka, M., Kitabayashi, C., Tsuji, F., Aono, H., Ishihara, K., Huseby, E., Betz, U. A. K., et al. (2007) · International Immunology · doi:10.1093/intimm/dxm045 · Cited by 268 · see citing works
Self-citationCells of the synovium in rheumatoid arthritis. T lymphocytes
Lundy, S. K., Sarkar, S., Tesmer, L. A., & Fox, D. (2007) · Arthritis Research & Therapy · doi:10.1186/ar2107 · Cited by 268 · see citing works
Interleukin-6 in rheumatoid arthritis
Nishimoto, N. (2006) · Current Opinion in Rheumatology · doi:10.1097/01.bor.0000218949.19860.d1 · Cited by 261 · see citing works
Hanada, T., Yoshida, H., Kato, S., Tanaka, K., Masutani, K., Tsukada, J., Nomura, Y., Mimata, H., Kubo, M., & Yoshimura, A. (2003) · Immunity · doi:10.1016/s1074-7613(03)00240-1 · Cited by 260 · see citing works
gp130 at the nexus of inflammation, autoimmunity, and cancer
Silver, J. S., & Hunter, C. A. (2010) · Journal of Leukocyte Biology · doi:10.1189/jlb.0410217 · Cited by 252 · see citing works
“Conversely, gp130 Y759 mutant mice, which have sustained signaling through gp130, develop autoimmune arthritis spontaneously, characterized by accumulation of activated T cells and myeloid cells, which is dependent on IL-6 and STAT3 [162, 163].”
BackgroundTargeting Interleukin-6: All the Way to Treat Autoimmune and Inflammatory Diseases
Tanaka, T., & Kishimoto, T. (2012) · International Journal of Biological Sciences · doi:10.7150/ijbs.4666 · Cited by 245 · see citing works
“For example, IL-6 blockade strategy demonstrably limited susceptibility to Castleman’s disease-like symptoms in IL-6 transgenic mice [35], as well as in various mouse models of rheumatoid arthritis [36-48], systemic lupus erythematosus [49-51], scleroderma [52, 53], C-peptide-induced myositis [54], experimental autoim…”
BackgroundUps and downs: The STAT1:STAT3 seesaw of Interferon and gp130 receptor signalling
Regis, G., Pensa, S., Boselli, D., Novelli, F., & Poli, V. (2008) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2008.06.004 · Cited by 237 · see citing works
Wong, P. K. K. (2006) · Journal of Clinical Investigation · doi:10.1172/jci25660 · Cited by 215 · see citing works
The Effect of Platelet-Rich Plasma Formulations and Blood Products on Human Synoviocytes
Braun, H., Kim, H.-J., Chu, C., & Dragoo, J. (2014) · American Journal of Sports Medicine · doi:10.1177/0363546514525593 · Cited by 219 · see citing works
“In addition to the significant postinjection pain reported after intra-articular LR-PRP treatment,(22) it is established that these cytokines incite and perpetuate inflammation and contribute to subsequent cartilage degradation(5,40) and, most significantly, that overexpression of TNF-a, IL-1b, and IL-6 is sufficient…”
BackgroundThe SH2 domain: versatile signaling module and pharmaceutical target.
Machida, K., & Mayer, B. (2005) · Biochimica et Biophysica Acta · doi:10.1016/j.bbapap.2004.10.005 · Cited by 218 · see citing works
Hepatic interleukin-7 expression regulates T cell responses.
Sawa, Y., Arima, Y., Ogura, H., Kitabayashi, C., Jiang, J.-J., Fukushima, T., Kamimura, D., Hirano, T., & Murakami, M. (2009) · Immunity · doi:10.1016/j.immuni.2009.01.007 · Cited by 203 · see citing works
“However, we recently showed that excessive IL-7 production in nonhematopoietic cells from F759 mutant mice, which show augmented IL-6-gp130-STAT3 signaling, contributes to the development of autoimmune arthritis (Atsumi et al., 2002; Sawa et al., 2006).”
BackgroundSelf-citationDimitriou, I. D., Clemenza, L., Scotter, A. J., Chen, G., Guerra, F. M., & Rottapel, R. K. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00659.x · Cited by 180 · see citing works
“Curiously, mice with mutated gp130 (Y757F), which prevents SOCS3 binding, develop a spontaneous RA-like phenotype (97).”
BackgroundInhibition of IL-6 for the treatment of inflammatory diseases
NISHIMOTO, N. (2004) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2004.03.005 · Cited by 200 · see citing works
Nowell, M., Richards, P. J., Fielding, C., Ognjanovic, S., Topley, N., Williams, A., Bryant-greenwood, G., & Jones, S. A. (2006) · Arthritis & Rheumatism · doi:10.1002/art.21942 · Cited by 200 · see citing works
Positive regulators of osteoclastogenesis and bone resorption in rheumatoid arthritis
Braun, T., & Zwerina, J. (2011) · Arthritis Research & Therapy · doi:10.1186/ar3380 · Cited by 202 · see citing works
Sano, S., Chan, K. S., & DiGiovanni, J. (2007) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2007.05.016 · Cited by 182 · see citing works
“But how does the Th17 shift occur? (3) Is Stat3 activation also involved in the development of arthritis in psoriatic patients? It was shown that knockin mice with a mutation gp130, in which Stat3 signaling was excessive under the gp130, spontaneously developed arthritis [69].”
BackgroundA genetics-led approach defines the drug target landscape of 30 immune-related traits
Fang, H., Wolf, H. D., Knezevic, B., Burnham, K. L., Osgood, J. A., Sanniti, A., Lara, A. L., Kasela, S., Cesco, S. D., Wegner, J. K., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0456-1 · Cited by 207 · see citing works
Suppression of cytokine signaling: The SOCS perspective
Linossi, E. M., Babon, J. J., Hilton, D. J., & Nicholson, S. E. (2013) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2013.03.005 · Cited by 192 · see citing works
“Consistent with this, aging gp130 mice are prone to spontaneously develop arthritis [40].”
BackgroundItoh, S., Udagawa, N., Takahashi, N., Yoshitake, F., Narita, H., Ebisu, S., & Ishihara, K. (2006) · Bone · doi:10.1016/j.bone.2006.02.074 · Cited by 187 · see citing works
“gp130 and gp130 mice that were backcrossed eight times to the C57BL/6 background were used [15].”
BackgroundMethodSelf-citationSawa, S.-I., Kamimura, D., Jin, G.-H., Morikawa, H., Kamon, H., Nishihara, M., Ishihara, K., Murakami, M., & Hirano, T. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20052187 · Cited by 176 · see citing works
“To investigate the in vivo function of these signaling pathways, we have established a series of knockin mice (27) and shown that one of these lines, gp130F759/F759 (F759), spontaneously develops an RA-like disease in a manner dependent on mature lymphocytes 1 yr after birth (28).”
BackgroundMethodInfluentialSelf-citationNegative regulation of cytokine signaling and immune responses by SOCS proteins.
Yoshimura, A., Nishinakamura, H., Matsumura, Y., & Hanada, T. (2005) · Arthritis Research · doi:10.1186/ar1741 · Cited by 162 · see citing works
Interleukin 6 in autoimmune and inflammatory diseases: a personal memoir
HIRANO, T. (2010) · Proceedings of the Japan Academy, Series B · doi:10.2183/pjab.86.717 · Cited by 172 · see citing works
Self-citationCadherin-11 regulates fibroblast inflammation
Chang, S., Noss, E., Chen, M., Gu, Z., Townsend, K. P., Grenha, R., León, L., Lee, S.-Y., Lee, D., & Brenner, M. (2011) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1019437108 · Cited by 170 · see citing works
Barkhausen, T., Tschernig, T., Rosenstiel, P., van Griensven, M., Vonberg, R.-P., Dorsch, M., Mueller-Heine, A., Chalaris, A., Scheller, J., Rose-John, S., et al. (2011) · Critical Care Medicine · doi:10.1097/ccm.0b013e318211ff56 · Cited by 169 · see citing works
Maeda, K., Mehta, H., Drevets, D., & Coggeshall, K. (2010) · Blood · doi:10.1182/blood-2009-07-230631 · Cited by 164 · see citing works
IL-6, IL-17 and STAT3: a holy trinity in auto-immunity?
Camporeale, A. (2012) · Frontiers in bioscience · doi:10.2741/4054 · Cited by 175 · see citing works
“While gp130 mice undergo a spontaneous lymphocyte-mediated rheumatoid arthritis-like joint disease (202), gp130 mice develop gastric tumours (203).”
BackgroundFibroblast‐like synoviocytes in inflammatory arthritis pathology: the emerging role of cadherin‐11
Chang, S. K., Gu, Z., & Brenner, M. B. (2009) · Immunological Reviews · doi:10.1111/j.0105-2896.2009.00854.x · Cited by 148 · see citing works
“ing downstream signals resulting from a point mutation of the gp130 subunit of IL-6R spontaneously developed autoimmune arthritis (39).”
BackgroundDevelopments in the scientific understanding of rheumatoid arthritis
Goronzy, J. J., & Weyand, C. M. (2009) · Arthritis Research & Therapy · doi:10.1186/ar2758 · Cited by 130 · see citing works
Negative regulation of cytokine signaling influences inflammation
Yoshimura, A., Mori, H., Ohishi, M., Aki, D., & Hanada, T. (2003) · Current Opinion in Immunology · doi:10.1016/j.coi.2003.09.004 · Cited by 126 · see citing works
Interleukin-6 trans-signaling in inflammatory bowel disease.
Mitsuyama, K., Sata, M., & Rose-John, S. (2006) · Cytokine & growth factor reviews · doi:10.1016/j.cytogfr.2006.09.003 · Cited by 122 · see citing works
“IL-6 has been reported to rescue T cells from apoptosis [67,68], and blockade of sIL-6R signaling in experimental models prevented disease onset by suppressing expression of the antiapoptotic regulators Bcl-xl and Bcl-2 [13].”
BackgroundInflammatory pathways in spondyloarthritis
Hreggvidsdottir, H. S., Noordenbos, T., & Baeten, D. (2013) · Molecular Immunology · doi:10.1016/j.molimm.2013.07.016 · Cited by 128 · see citing works
“…in prolonged STAT3 activation develop RA-like arthritis ccompanied by autoantibody production (Atsumi et al., 2002). eletion of STAT3 binding sites of gp130 results on the other hand n sustained SHP-2/ras/Erk signalling and the mice develop…”
BackgroundThe JAK/STAT pathway in rheumatoid arthritis: Pathogenic or protective?
Ivashkiv, L. B., & Hu, X. (2003) · Arthritis & Rheumatism · doi:10.1002/art.11095 · Cited by 103 · see citing works
The role of antibodies in mouse models of rheumatoid arthritis, and relevance to human disease.
Monach, P., Benoist, C., & Mathis, D. (2004) · Advances in Immunology · doi:10.1016/s0065-2776(04)82005-4 · Cited by 118 · see citing works
Haroon, F., Drögemüller, K., Händel, U., Brunn, A., Reinhold, D., Nishanth, G., Müller, W., Trautwein, C., Ernst, M., Deckert, M., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1001135 · Cited by 118 · see citing works
“Noteworthily, mice lacking gp130-SHP2/Ras/ERK signaling in all cells may develop spontaneous autoimmune arthritis due to excessive activation of the STAT1/3 pathway in nonhematopoietic cells (53).”
BackgroundOhsugi, Y. (2007) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.30.2001 · Cited by 100 · see citing works
Disease-association analysis of an inflammation-related feedback loop
Murakami, M., Harada, M., Kamimura, D., Ogura, H., Okuyama, Y., Kumai, N., Okuyama, A., Singh, R., Jiang, J.-J., Atsumi, T., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.01.028 · Cited by 110 · see citing works
“As these mice age, they spontaneously develop an MHC class II-associated, IL-6-dependent, tissue-specific joint disease (F759 arthritis) that resembles rheumatoid arthritis (Atsumi et al., 2002; Sawa et al., 2006).”
BackgroundMethodSelf-citationKomatsu, N., & Takayanagi, H. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00077 · Cited by 98 · see citing works
“…is also supported by T-cell-dependent models such as the SKG mouse, which has a mutation in ZAP70 (Sakaguchi et al., 2003), the F759 mouse with a mutation in the gp130 IL-6 receptor subunit (Atsumi et al., 2002), and the IL-1 receptor antagonist (IL-1Ra)-deficient mouse (Horai et al., 2000).”
Backgroundde Hooge, A. S. K., van de Loo, F. A. J., Koenders, M. I., Bennink, M. B., Arntz, O. J., Kolbe, T., & van den Berg, W. B. (2004) · Arthritis & Rheumatism · doi:10.1002/art.20302 · Cited by 103 · see citing works
Interleukin-27 inhibits ectopic lymphoid-like structure development in early inflammatory arthritis
Jones, G. W., Bombardieri, M., Greenhill, C., McLeod, L., Nerviani, A., Rocher-Ros, V., Figueras, A. C., Williams, A. S., Pitzalis, C., Jenkins, B. J., et al. (2015) · The Journal of Experimental Medicine · doi:10.1084/jem.20132307 · Cited by 105 · see citing works
“In experimental arthritis, gp130-mediated STAT3 signaling exacerbates pathology (Atsumi et al., 2002; Nowell et al., 2009), and synovial tissues containing lymphoid follicles show enhanced STAT3 activity (Sawa et al.”
BackgroundResultMurakami, M., Okuyama, Y., Ogura, H., Asano, S., Arima, Y., Tsuruoka, M., Harada, M., Kanamoto, M., Sawa, Y., Iwakura, Y., et al. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20100900 · Cited by 100 · see citing works
“As these mice age, they spontaneously develop an RA-like MHC II–associated tissuespecific disease, indicating that constitutive activation of IL-6 signaling is involved in the development of some autoimmune diseases (Atsumi et al., 2002; Sawa et al., 2006).”
Self-citationADAM17 Activity and IL-6 Trans-Signaling in Inflammation and Cancer
Schumacher, N., & Rose‐John, S. (2019) · Cancers · doi:10.3390/cancers11111736 · Cited by 103 · see citing works
“These mice can still activate the STAT1/STAT3 pathway [86,87].”
BackgroundInfluentialKomatsu, N., & Takayanagi, H. (2012) · Advances in immunology · doi:10.1016/b978-0-12-394299-9.00002-3 · Cited by 88 · see citing works
“Arthritis in IL-1Ra-deficient mice (Horai et al., 2004) and F759 mice (Atsumi et al., 2002) is also lymphocyte-mediated, as mice with a RAG-deficient background fail to develop arthritis.”
SOCS3 revisited: a broad regulator of disease, now ready for therapeutic use?
Mahony, R., Ahmed, S., Diskin, C., & Stevenson, N. J. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2234-x · Cited by 92 · see citing works
Jenkins, B. J., Roberts, A. W., Greenhill, C., Najdovska, M., Lundgren–May, T., Robb, L. G., Grail, D., & Ernst, M. (2006) · Blood · doi:10.1182/blood-2006-08-040352 · Cited by 90 · see citing works
“By analogy with the lymphoid abnormalities in gp130 mice, which also display elevated STAT3 activity, the abnormal distribution of thymocytes and peripheral T cells in our gp130 mice is likely to result from both impairment of negative selection of immature thymic CD4CD8 T cells and clonal deletion of peripheral T cel…”
BackgroundTargeting IL-17 and Th17 Cells in Rheumatoid Arthritis
Sarkar, S., & Fox, D. A. (2010) · Rheumatic Disease Clinics of North America · doi:10.1016/j.rdc.2010.02.006 · Cited by 84 · see citing works
“develop spontaneous arthritis due to prolonged unrestrained stimulation of this receptor.(135) IL-6 is elevated in the synovial fluid and sera of patients with RA, and its level correlates with disease activity.”
Role for interleukin-6 in structural joint damage and systemic bone loss in rheumatoid arthritis
Goff, B. L., Blanchard, F., Berthelot, J., Heymann, D., & Maugars, Y. (2010) · Joint Bone Spine · doi:10.1016/j.jbspin.2010.03.002 · Cited by 91 · see citing works
c-Cbl-Dependent Monoubiquitination and Lysosomal Degradation of gp130
Tanaka, Y., Tanaka, N., Saeki, Y., Tanaka, K., Murakami, M., Hirano, T., Ishii, N., & Sugamura, K. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.01784-07 · Cited by 82 · see citing works
“ing human wild-type gp130 (gp130) or a mutant gp130 (gp130) (6), a c-Cbl-deficient (c-Cbl / ) MEF, a wild-type c-Cbl-tranfected c-Cbl / (cCbl) MEF (17), and a retroviral packaging cell line, Phoenix-Ampho (Orbi-”
Self-citationSuppressors of cytokine signaling in health and disease
Tan, J. C., & Rabkin, R. (2005) · Pediatric nephrology (Berlin, West) · doi:10.1007/s00467-004-1766-8 · Cited by 86 · see citing works
“For example, mice with mutated gp130, in which the SHP2/SOCS3 binding site was disrupted, developed joint disease similar to rheumatoid arthritis with increased production of Th1type cytokines [58].”
BackgroundFas (CD95)-related apoptosis and rheumatoid arthritis.
Peng, S. L. (2006) · Rheumatology · doi:10.1093/rheumatology/kei113 · Cited by 84
NEDD4 Is Involved in Inflammation Development during Keloid Formation
Fujita, M., Yamamoto, Y., Jiang, J., Atsumi, T., Tanaka, Y., Ohki, T., Murao, N., Funayama, E., Hayashi, T., Osawa, M., et al. (2018) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2018.07.044 · Cited by 93 · see citing works
Self-citationLessons from animal models of arthritis over the past decade
Berg, W. (2009) · Arthritis Research & Therapy · doi:10.1186/ar2803 · Cited by 65 · see citing works
Johnston, J., & O'Shea, J. (2003) · Nature Immunology · doi:10.1038/ni0603-507 · Cited by 77 · see citing works
Temporal Expression of Growth Factors Triggered by Epiregulin Regulates Inflammation Development
Harada, M., Kamimura, D., Arima, Y., Kohsaka, H., Nakatsuji, Y., Nishida, M., Atsumi, T., Meng, J., Bando, H., Singh, R., et al. (2015) · Journal of Immunology · doi:10.4049/jimmunol.1400562 · Cited by 72 · see citing works
“As these mice age, they spontaneously develop an MHC class II–associated, IL-6–dependent joint disease (F759 arthritis) that resembles RA (8, 14).”
BackgroundMethodSelf-citationJAK/STAT Activation: A General Mechanism for Bone Development, Homeostasis, and Regeneration
Damerau, A., Gaber, T., Ohrndorf, S., & Hoff, P. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21239004 · Cited by 71 · see citing works
Lee, J., Nakagiri, T., Oto, T., Harada, M., Morii, E., Shintani, Y., Inoue, M., Iwakura, Y., Miyoshi, S., Okumura, M., et al. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1103613 · Cited by 72 · see citing works
“The F759 mice showed enhanced IL-6 signaling due to a lack of gp130-dependent suppressor of cytokine signaling 3-mediated negative feedback (20).”
BackgroundSelf-citationConditional gp130 deficient mouse mutants
Fasnacht, N., & Müller, W. (2008) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2008.07.001 · Cited by 60 · see citing works
The Pathological and Physiological Roles of IL-6 Amplifier Activation
Murakami, M., & Hirano, T. (2012) · International Journal on Biological Sciences · doi:10.7150/ijbs.4828 · Cited by 69 · see citing works
“All F759 mice were found to have a rheumatoid arthritis-like disease at about 12-18 months after birth [19](Figure 1).”
BackgroundSelf-citationIL-6 positively regulates Foxp3+CD8+ T cells in vivo.
Nakagawa, T., Tsuruoka, M., Ogura, H., Okuyama, Y., Arima, Y., Hirano, T., & Murakami, M. (2010) · International Immunology · doi:10.1093/intimm/dxp119 · Cited by 69 · see citing works
Self-citationBrender, C., Tannahill, G. M., Jenkins, B. J., Fletcher, J. G., Columbus, R., Saris, C. J. M., Ernst, M., Nicola, N. A., Hilton, D. J., Alexander, W. S., et al. (2007) · Blood · doi:10.1182/blood-2006-08-041541 · Cited by 64 · see citing works
SHP2 forecast for the immune system: fog gradually clearing.
Salmond, R. J., & Alexander, D. (2006) · Trends in immunology · doi:10.1016/j.it.2006.01.007 · Cited by 69 · see citing works
Regulation of TLR signaling and inflammation by SOCS family proteins
Yoshimura, A., Ohishi, H. M. M., Aki, D., & Hanada, T. (2004) · Journal of Leukocyte Biology · doi:10.1189/jlb.0403194 · Cited by 63 · see citing works
“For example, a mouse line with a mutated gp130, to which SOCS3 cannot bind, developed a RA-like joint disease with increased production of Th1-type cytokines and Igs of the IgG2a and IgG2b classes [ 58 ].”
BackgroundInterpreting mixed signals: the cell's cytokine conundrum
Delgoffe, G. M., Murray, P. J., & Vignali, D. A. A. (2011) · Current Opinion in Immunology · doi:10.1016/j.coi.2011.07.013 · Cited by 66 · see citing works
Nakamura, K., Kouro, T., Kincade, P. W., Malykhin, A., Maeda, K., & Coggeshall, K. M. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20031193 · Cited by 53 · see citing works
“Lastly, transgenic animals harboring a Y to F point mutant IL-6 receptor spontaneously develop rheumatoid arthritis (34).”
BackgroundCytokines in the rheumatic diseases.
Arend, W., & Gabay, C. (2004) · Rheumatic Disease Clinics of North America · doi:10.1016/s0889-857x(03)00115-7 · Cited by 65 · see citing works
“Through gp130, IL-6 induces two signal transduction pathways, one of which may be stimulatory to inflammatory responses and the other may be inhibitory [88].”
BackgroundTargeting IL-6 or IL-6 Receptor in Rheumatoid Arthritis: What’s the Difference?
Avcı, A., Feist, E., & Burmester, G. (2018) · BioDrugs · doi:10.1007/s40259-018-0320-3 · Cited by 58 · see citing works
Forrai, A., Boyle, K., Hart, A. H., Hartley, L., Rakar, S., Willson, T. A., Simpson, K., Roberts, A. W., Alexander, W. S., Voss, A. K., et al. (2005) · Stem Cells · doi:10.1634/stemcells.2005-0323 · Cited by 60 · see citing works
Kumanogoh, A., Shikina, T., Watanabe, C., Takegahara, N., Suzuki, K., Yamamoto, M., Takamatsu, H., Prasad, D. V., Mizui, M., Toyofuku, T., et al. (2005) · International Immunology · doi:10.1093/intimm/dxh307 · Cited by 58 · see citing works
“Titers of serum antibodies Rheumatoid factor (RF) for mouse Ig of both IgM and IgG classes, anti-dsDNA antibodies and anti-ssDNA antibodies were measured using commercial ELISA kits (Shibayagi, Japan) as described ( 13 ).”
MethodRaimondo, A., Lembo, S., Caprio, R. D., Donnarumma, G., Monfrecola, G., Balato, N., Ayala, F., & Balato, A. (2017) · European Journal of Immunology · doi:10.1002/eji.201646774 · Cited by 54 · see citing works
Immune-mediated pathways in chronic inflammatory arthritis
Gorman, C., & Cope, A. P. (2008) · Best Practice & Research Clinical Rheumatology · doi:10.1016/j.berh.2008.01.003 · Cited by 44 · see citing works
Pathophysiological roles for IL-18 in inflammatory arthritis
Matsui, K., Tsutsui, H., & Nakanishi, K. (2003) · Expert opinion on therapeutic targets · doi:10.1517/14728222.7.6.701 · Cited by 54 · see citing works
Murakami, M., & Hirano, T. (2011) · Frontiers in Immunology · doi:10.3389/fimmu.2011.00022 · Cited by 53 · see citing works
“As these mice age, they spontaneously develop a RA-like tissue-specific disease, indicating that constitutive activation of IL-6 signaling is involved in the development of certain autoimmune diseases (Atsumi et al., 2002).”
Self-citationPsoriatic inflammation facilitates the onset of arthritis in a mouse model.
Yamamoto, M., Nakajima, K., Takaishi, M., Kitaba, S., Magata, Y., Kataoka, S., & Sano, S. (2015) · Journal of Investigative Dermatology · doi:10.1038/jid.2014.426 · Cited by 49 · see citing works
Hanada, T., Kinjyo, I., Inagaki-Ohara, K., & Yoshimura, A. (2003) · Springer eBooks · doi:10.1007/s10254-003-0015-z · Cited by 43 · see citing works
SHP-2 in Lymphocytes' Cytokine and Inhibitory Receptor Signaling
Niogret, C., Birchmeier, W., & Guarda, G. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02468 · Cited by 48 · see citing works
Mouse models of psoriasis and their relevance
Nakajima, K., & Sano, S. (2018) · Journal of dermatology (Print) · doi:10.1111/1346-8138.14112 · Cited by 48 · see citing works
Th17 in Animal Models of Rheumatoid Arthritis
Hashimoto, M. (2017) · Journal of Clinical Medicine · doi:10.3390/jcm6070073 · Cited by 48 · see citing works
“In gp130 F759/F759 knock-in (gp130 F759) mice, tyrosine 759 (Y759 in human gp130) in the SHP2-binding site of gp130 is replaced with phenylalanine (F) [13].”
Background
- Authors
- Atsumi, T., Ishihara, K., Kamimura, D., Ikushima, H., Ohtani, T., Hirota, S., Kobayashi, H., Park, S.-J., Saeki, Y., Kitamura, Y., & Hirano, T.
- Affiliations
- RIKEN (JP)
- The University of Osaka (JP)
- 1Department of Molecular Oncology (C7), Graduate School of Medicine
- 2Department of Pathology (C2), Graduate School of Medicine
- Kowa (Japan) (JP)
- 3Department of Molecular Medicine (C4), Graduate School of Medicine
- ORCID
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2002-09-30
- Volume
- 196
- Issue
- 7
- Pages
- 979-990
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2194024
- OpenAlex
- W2145478309
- Cited by
- 225
- References
- 49
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 4 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 13 · 2018: 7 · 2017: 7 · 2016: 4 · 2015: 12 · 2014: 10 · 2013: 11 · 2012: 13
- FWCI
- 6.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- gp130, rheumatoid arthritis, autoimmune arthritis, autoantibodies, thymic selection, Fas ligand, activation-induced cell death, STAT3 signaling
- MeSH terms
- Animals, Antibody Formation, Arthritis, Experimental, Base Sequence, Binding Sites, Bone and Bones, Enterotoxins, Lymph Nodes, Mice, Inbred C57BL, Mice, Transgenic, Staphylococcus aureus, T-Lymphocytes, Tyrosine, CD4-Positive T-Lymphocytes, Polymerase Chain Reaction, Apoptosis, Point Mutation, DNA Primers, Superantigens, Amino Acid Substitution, Receptors, Interleukin-6, Protein Subunits, Mice
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 ›
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