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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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“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]
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“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).”
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“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
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“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.
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“This is in sharp contrast to the arthritis that develops in TNF AUrich elements-deficient mice, which is independent of lymphocytes (9).”
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Self-citationExcessive production of interleukin 6/B cell stimulatory factor-2 in rheumatoid arthritis
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BackgroundSelf-citation
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Items 101–200 of 201
IL-6 Mediates the Susceptibility of Glycoprotein 130 Hypermorphs to Toxoplasma gondii
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“In contrast, gp130 Y759F mice develop an autoimmune arthritis driven by STAT3-mediated overproduction of IL-7 (14, 15).”
BackgroundEvaluation of anti-IL-6 monoclonal antibody therapy using murine type II collagen-induced arthritis
Liang, B., Song, Z., Wu, B., Gardner, D., Shealy, D., Song, X.-Y. R., & Wooley, P. (2009) · Journal of Inflammation · doi:10.1186/1476-9255-6-10 · Cited by 46
“IL-6 receptor subunit gp130 transgenic mice that have excess spontaneous IL-6 signaling have been reported to develop a joint disease that is similar to RA which is triggered by lymphocyte activation and accompanied by autoantibody formation [11].”
BackgroundNegative regulation of cytokine signaling and inflammatory diseases
Inagaki-Ohara, K. (2003) · Current Opinion in Pharmacology · doi:10.1016/s1471-4892(03)00070-5 · Cited by 41
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“A single point mutation in the IL-6 receptor, which affected its signal transduction pathway, caused experimental autoimmune arthritis [26,27].”
BackgroundThe immediate early genes Fos and Egr1 become STAT1 transcriptional targets in the absence of STAT3
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“Likewise, MAPK activation downstream of several IL-6 family cytokines, sharing the gp130 receptor subunit, is prolonged in the absence of STAT3 signaling, both in vitro and in vivo [7–9].”
BackgroundIL-17 producing T cells in mouse models of multiple sclerosis and rheumatoid arthritis
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“GP130 Mutation in SH2 domain of IL-6 receptor subunit gp130 100% + + [65]”
BackgroundCitrullination of Self‐Proteins and Autoimmunity
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“Its overexpression appears to inhibit TCR signaling and T helper cell proliferation (75, 77), whereas decreased SOCS3 activity has been implicated in murine autoimmune arthritis (81-83) and in human RA (48, 78-80).”
BackgroundKyo, F., Futani, H., Matsui, K., Terada, M., Adachi, K., Nagata, K., Sano, H., Tateishi, H., Tsutsui, H., & Nakanishi, K. (2005) · Arthritis & Rheumatism · doi:10.1002/art.21213 · Cited by 36
Mechanism of attenuation of leptin signaling under chronic ligand stimulation
Knobelspies, H., Zeidler, J., Hekerman, P., Bamberg‐Lemper, S., & Becker, W. B. (2010) · BMC Biochemistry · doi:10.1186/1471-2091-11-2 · Cited by 31
“The disruption of the negative feedback on gp130-dependent STAT signaling causes STAT3 hyperactivation, and these mice develop a broad spectrum of hematopoietic abnormalities, including splenomegaly, lymphadenopathy, thrombocytosis and autoimmune arthritis [51-54].”
Making sense of IL‐6 signalling cues in pathophysiology
Millrine, D., Jenkins, R. L., Hughes, S. T. O., & Jones, S. A. (2021) · FEBS Letters · doi:10.1002/1873-3468.14201 · Cited by 39
“In murine models, STAT1 activities often reduce arthritis severity [189 – 191], whereas STAT3 regulates leukocyte recruitment and activation, synovial hyperplasia and joint erosion [98,178,184,192 – 198].”
BackgroundResultYamana, J., Yamamura, M., Okamoto, A., Aita, T., Iwahashi, M., Sunahori, K., & Makino, H. (2004) · Arthritis Research & Therapy · doi:10.1186/ar1445 · Cited by 31
“Furthermore, the significance of persistent STAT3 signaling in Th1-cell-dominated autoimmune arthritis has been suggested by studies of the gp130F759/F759 mice, in which the Src homology phosphatase-2 binding site of gp130 (the transmembrane glycoprotein β subunit of the IL-6 family cytokine receptor), tyrosine 759, w…”
BackgroundCytokine signal regulation and autoimmune disorders
Nishimoto, N. (2005) · Autoimmunity · doi:10.1080/08916930500124106 · Cited by 32
“Mice with a point mutation of Tyr-759 in IL-6 family cytokine receptor subunit gp130, a binding site of src homology 2 domain-bearing protein tyrosine phosphatase (SHP)-2, have been shown to develop autoimmune arthritis [36].”
BackgroundProtein tyrosine phosphatases in skeletal development and diseases
Yang, H., Wang, L., Shigley, C., & Yang, W. (2022) · Bone Research · doi:10.1038/s41413-021-00181-x · Cited by 32
“SHP2 reportedly negatively modulates IL6-evoked STAT3 phosphorylation and activation upon binding to gp130Y759.(90,91) Conceivably, SHP2 might influence OB differentiation and function by modifying multiple signaling pathways, including the ERK, AKT, and STAT3 pathways.”
BackgroundSabharwal, L., Kamimura, D., Meng, J., Bando, H., Ogura, H., Nakayama, C., Jiang, J., Kumai, N., Suzuki, H., Atsumi, T., et al. (2014) · The Journal of Biochemistry · doi:10.1093/jb/mvu057 · Cited by 34
“As expected, F759 mice produce autoantibodies, and finally develop RA-like joint diseases with age spontaneously (18).”
BackgroundSelf-citationInfection-immunity liaison: pathogen-driven autoimmune-mimicry (PDAIM).
Saeki, Y., & Ishihara, K. (2014) · Autoimmunity Reviews · doi:10.1016/j.autrev.2014.08.024 · Cited by 31
Self-citationWakasa-Morimoto, C., Toyosaki-Maeda, T., Matsutani, T., Yoshida, R., Nakamura-Kikuoka, S., Maeda-Tanimura, M., Yoshitomi, H., Hirota, K., Hashimoto, M., Masaki, H., et al. (2008) · International Immunology · doi:10.1093/intimm/dxn091 · Cited by 31
“... cytokines, for example systemic overproduction of transgenic TNF-a or IL-1 almost exclusively produces chronic arthritis even in mice deficient of both T and B cells (37‐39); similarly, systemic deficiency of the IL-1R antagonist, and resulting overproduction of IL-1, or systemic alteration of signal transduction…”
BackgroundRevisiting the 1986 Molecular Cloning of Interleukin 6
Hirano, T. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00456 · Cited by 31
Self-citationAndersson, K., Cavallini, N. F., Hu, D., Brisslert, M., Cialic, R., Valadi, H., Erlandsson, M. C., Silfverswärd, S. T., Pullerits, R., Kuchroo, V. K., et al. (2015) · Molecular Medicine · doi:10.2119/molmed.2015.00057 · Cited by 33
Ota, M., Tanaka, Y., Nakagawa, I., Jiang, J., Arima, Y., Kamimura, D., Onodera, T., Iwasaki, N., & Murakami, M. (2019) · Arthritis & Rheumatology · doi:10.1002/art.41182 · Cited by 35
“naling caused by the lack of a suppressor of cytokine signaling 3–binding site on the IL6 receptor gp130 (21,23).”
BackgroundSelf-citationThe gateway theory: bridging neural and immune interactions in the CNS
Kamimura, D., Yamada, M., Harada, M., Sabharwal, L., Meng, J., Bando, H., Ogura, H., Atsumi, T., Arima, Y., & Murakami, M. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00204 · Cited by 35
Self-citationRidgley, L. A., Anderson, A. E., Maney, N. J., Naamane, N., Skelton, A. J., Lawson, C. A., Emery, P., Isaacs, J. D., Carmody, R. J., & Pratt, A. G. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01535 · Cited by 27
Wang, L., Yang, H., Huang, J., Pei, S., Wang, L., Feng, J. Q., Jing, D., Zhao, H., Kronenberg, H. M., Moore, D. C., et al. (2021) · Bone Research · doi:10.1038/s41413-020-00129-7 · Cited by 28
“Our findings are consistent with published work showing that SHP2 downregulates STAT3 phosphorylation(72,73) and that mice bearing gp130F759/F759 mutations that no longer bind SHP2 have enhanced STAT3 activation and osteoclast formation and consequently BMD reduction.(74,75) STAT3 is essential for gp130-mediated osteo…”
ResultCardiac phenotype in mouse models of systemic autoimmunity
Sanghera, C., Wong, L. M., Panahi, M., Sintou, A., Hasham, M. G., & Sattler, S. (2019) · Disease Models & Mechanisms · doi:10.1242/dmm.036947 · Cited by 36
“Histologic examination showed leukocytes infiltrating the joint space, hyperplasia of the synovium with pannus formation, cartilage and bone destruction, and bony ankyloses (Box 1) (Atsumi et al., 2002).”
Zabala, W., Cruz, R., Acosta, M. B., Chaparro, M., Panés, J., Echarri, A., Esteve, M., Carpio, D., Andreu, M. G., García-Planella, E., et al. (2013) · Pharmacogenomics · doi:10.2217/pgs.13.38 · Cited by 20
Interleukin 6: The biology behind the therapy
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“The development of arthritis in gp130F759 is Rag2-dependent, but the Y759F mutation in non-haematopoietic cells is sufficient.(17) Several pathophysiological mechanisms have been reported.”
BackgroundSelf-citationATP spreads inflammation to other limbs through crosstalk between sensory neurons and interneurons
Hasebe, R., Murakami, K., Harada, M., Halaka, N., Nakagawa, H., Kawano, F., Ohira, Y., Kawamoto, T., Yull, F. E., Blackwell, T. S., et al. (2022) · The Journal of Experimental Medicine · doi:10.1084/jem.20212019 · Cited by 21
“F759 mice are a spontaneous RAmodel dependent on the IL-6 amplifier in the joints (Atsumi et al., 2002; Murakami et al., 2011; Ogura et al., 2008).”
BackgroundSelf-citationInoue, A., Matsumoto, I., Tanaka, Y., Umeda, N., Tanaka, Y., Mihara, M., Takahashi, S., & Sumida, T. (2012) · Arthritis & Rheumatism · doi:10.1002/art.34666 · Cited by 18
“Exacerbation of CIA in TIARP / mice, with increased numbers of antigen-specific Th1 and Th17 cells in LNs, enhanced serum levels of IL-6, and infiltration of macrophages and neutrophils into the joints.”
BackgroundInfluentialNegative Regulation of Cytokine Signaling
Yoshimura, A. (2005) · Clinical Reviews in Allergy & Immunology · doi:10.1385/criai:28:3:205 · Cited by 47
Ishihara, K. (2004) · International Immunology · doi:10.1093/intimm/dxh045 · Cited by 21
Self-citationOhsugi, Y. (2019) · Journal of Translational Autoimmunity · doi:10.1016/j.jtauto.2019.100030 · Cited by 17
The Role of the Transcriptional Regulation of Stromal Cells in Chronic Inflammation
Valín, Á., & Pablos, J. L. (2015) · Biomolecules · doi:10.3390/biom5042723 · Cited by 17
“IL-6- and gp130-mediated STAT3 activation are enhanced, developing a RA-like disease that depends on mature lymphocytes [89].”
BackgroundCellular imaging in rheumatic diseases
Benson, R. A., McInnes, I. B., Brewer, J. M., & Garside, P. (2015) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2015.34 · Cited by 19
The Systemic and Pulmonary Immune Response to Staphylococcal Enterotoxins
Kumar, S., Ménoret, A., Ngoi, S., & Vella, A. (2010) · Toxins · doi:10.3390/toxins2071898 · Cited by 17
“signaling can also inhibit SEB-induced T cell peripheral deletion [41].”
BackgroundTsuji, F., Yoshimi, M., Katsuta, O., Takai, M., Ishihara, K., & Aono, H. (2009) · BMC Musculoskeletal Disorders · doi:10.1186/1471-2474-10-23 · Cited by 17
“Importantly, gp130F759 in the mixed background with 129 and C57BL/6 spontaneously develop a RA-like autoimmune disease in old age [13].”
BackgroundSelf-citationBmi1 Regulates IκBα Degradation via Association with the SCF Complex
Okuyama, Y., Tanaka, Y., Jiang, J., Kamimura, D., Nakamura, A., Ota, M., Ohki, T., Higo, D., Ogura, H., Ishii, N., et al. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1701223 · Cited by 22
“F759 mice were backcrossed with C57BL/6 mice for more than 10 generations (32).”
BackgroundSelf-citationOhtsuji, M., Lin, Q., Nishikawa, K., Ohtsuji, N., Okazaki, H., Tsurui, H., Amano, H., Shirai, T., Nishimoto, N., Nishimura, H., et al. (2015) · Modern Rheumatology · doi:10.3109/14397595.2014.950035 · Cited by 16
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“Shouda et al (30) demonstrated that removing the functional domain of STAT3 attenuated CIA, and the hyperactivation of STAT3 may result in the spontaneous development of autoimmune arthritis (31).”
Targeting of Interleukin-6 for the Treatment of Rheumatoid Arthritis: A Review and Update
Tanaka, T., Ogata, A., & Kishimoto, T. (2014) · doi:10.4172/2161-1149.s4-002 · Cited by 15
“indicating that constitutive activation of IL-6 signaling is involved in the development of RA-like features [70].”
BackgroundGulko, P. (2007) · Genes and Immunity · doi:10.1038/sj.gene.6364419 · Cited by 14
Atsumi, T., Sato, M., Kamimura, D., Moroi, A., Iwakura, Y., Betz, U. A. K., Yoshimura, A., Nishihara, M., Hirano, T., & Murakami, M. (2008) · International Immunology · doi:10.1093/intimm/dxn125 · Cited by 20
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CD4+T-cell subsets in rheumatoid arthritis
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New insight into the role of SOCS family in immune regulation and autoimmune pathogenesis
Liu, S., Wang, M., Xu, L., Deng, D., Lu, L., Tian, J., Zhou, D., & Rui, K. (2025) · Journal of Advanced Research · doi:10.1016/j.jare.2025.05.020 · Cited by 13
“…and raised bone deterioration [122]. gp130 F759 mice with tyrosine residue Y759 of gp130 mutated to phenylalanine (F759) spontaneously develop an RA-like phenotype, which is attributed to the inability of SOCS3 to negatively regulate gp130-stimulated STAT3 activation after the Y759 mutation [123].”
A Systems Model of Phosphorylation for Inflammatory Signaling Events
Sadreev, I. I., Chen, M. Z. Q., Welsh, G. I., Umezawa, Y., Kotov, N. V., & Valeyev, N. V. (2014) · PLoS ONE · doi:10.1371/journal.pone.0110913 · Cited by 11
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Expression and function of cell cycle proteins in rheumatoid arthritis synovial tissue.
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Altered signalling thresholds in T lymphocytes cause autoimmune arthritis
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“In their report, Hirano and colleagues [3] reflect upon the diverse array of engineered mutant strains that induce spontaneous inflammatory arthritis and consider whether this might reflect either the heterogeneity of the human disease we recognize as RA, or the great complexity that underlies the disease process.”
BackgroundRare variants and HLA haplotypes associated in patients with neuromyelitis optica spectrum disorders
Tabansky, I., Tanaka, A., Wang, J., Zhang, G., Dujmović, I., Mader, S., Jeganathan, V., DeAngelis, T., Funaro, M. G., Harel, A., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.900605 · Cited by 12
“Mutations of IL6ST in mice can result in a hyper-responsive T cell phenotype , and deve lopment o f an ar thr i t i s - l i ke autoimmune disease in mice (85).”
BackgroundGateway reflexes: A new paradigm of neuroimmune interactions
Ohki, T., Kamimura, D., Arima, Y., & Murakami, M. (2017) · Clinical and Experimental Neuroimmunology · doi:10.1111/cen3.12378 · Cited by 10
“Interestingly, F759 mice developed a spontaneous rheumatoid arthritis-like joint disease and autoantibody production.(31) These phenomena are consistent with”
BackgroundSelf-citationThe Negative Regulation of JAK/STAT Signaling
Murphy, J. M., Tannahill, G. M., Hilton, D. J., & Greenhalgh, C. J. (2010) · Elsevier eBooks · doi:10.1016/b978-0-12-374145-5.00064-4 · Cited by 12
Endogenous antigens shape the transcriptome and TCR repertoire in an autoimmune arthritis model
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“These severe inflammation causes ankylosis in the large joints (Atsumi et al. 2002).”
BackgroundHada, Y., Uchida, H. A., Mukai, T., Kojima, F., Yoshida, M., Takeuchi, H., Kakio, Y., Otaka, N., Morita, Y., & Wada, J. (2020) · Clinical Science · doi:10.1042/cs20201036 · Cited by 10
Characterization of a novel and spontaneous mouse model of inflammatory arthritis
Cuzzocrea, S. (2011) · Arthritis Research & Therapy · doi:10.1186/ar3434 · Cited by 8
“in females has been reported for both the SKG [7] and gp130Y759F models [9].”
Characterization of a novel and spontaneous mouse model of inflammatory arthritis
Adipue, I. A., Wilcox, J., King, C., Rice, C., Shaum, K. M., Suard, C. M., ten Brink, E., Miller, S. D., & Mcmahon, E. (2011) · Arthritis Research & Therapy · doi:10.1186/ar3399 · Cited by 8
“RA patients also have slightly increased serum Ig levels [51], and researchers who have studied several spontaneous mouse models of arthritis, including the K/ BxN [32], gp130[35] and IL-1R antagonist deficiency models [34], have reported increases in IgG1 specifically.”
BackgroundResultInfluentialGrasp a pTyr-Peptide by Its SOCS
Hirano, T., & Murakami, M. (2006) · Developmental Cell · doi:10.1016/j.devcel.2006.04.011 · Cited by 8
Self-citationIL-6 and Inflammatory Diseases
Kamimura, D., Arima, Y., Hirano, T., Ogura, H., & Murakami, M. (2013) · Springer eBooks · doi:10.1007/978-4-431-54442-5_2 · Cited by 9
Self-citationFrey, O., Hückel, M., Gajda, M., Petrow, P., & Bräuer, R. (2018) · Arthritis Research & Therapy · doi:10.1186/s13075-018-1720-y · Cited by 7
Targeting Growth Factors in Arthritis: A Rational for Restoring the IGF-I Response in Chondrocytes
van de Loo, F. A. J., Veenbergen, S., & van den Berg, W. (2008) · Current Rheumatology Reviews · doi:10.2174/157339708786263861 · Cited by 3
“Mice with this point mutation developed RA-like joint disease accompanied by autoantibody production and increased T-cell activation [60, 61].”
BackgroundTocilizumab for the treatment of rheumatoid arthritis
Mima, T., & Nishimoto, N. (2008) · Expert Review of Clinical Immunology · doi:10.1586/1744666x.4.2.165 · Cited by 7
Regulators of cytokine signalling in rheumatoid arthritis
Rahman, A. (2007) · Lara D. Veeken · doi:10.1093/rheumatology/kem285 · Cited by 7
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Tocilizumab in Pediatric Rheumatology: The Clinical Experience
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Ishihara, K., & Igarashi, H. (2012) · InTech eBooks · doi:10.5772/29113 · Cited by 5
“, 2000) lacking a physiological negative feedback molecule, and in gp130F759 with a defective, intracellular negative-regulatory signaling pathway (Atsumi et al., 2002; Ohtani et al., 2000).”
BackgroundSelf-citationWhat Animal Models are Best to Test Novel Rheumatoid Arthritis Therapies
Wooley, P. (2008) · doi:10.2174/157339708786263898 · Cited by 5
Naïve arthritogenic SKG T cells have a defect in anergy and a repertoire pruned by superantigenPreprint
Ashouri, J. F., McCarthy, E. E., Yu, S., Perlmutter, N., Lin, C., DeRisi, J. L., Ye, C., & Weiss, A. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.01.13.476250 · Cited by 5
“Its expression has a strong inverse correlation with murine arthritis severity (48-50).”
BackgroundAkabane, K., Murakami, K., & Murakami, M. (2023) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2023.2225215 · Cited by 1
“This accumulation of activated CD4+ T cells and other immune cells raises the levels of various cytokines, such as IL−17A, TNF-α, and IL−6, further activating the NF-κB and STAT3 pathways in synovial fibroblasts, chondrocytes, and endothelial cells [2,16,27,28].”
BackgroundJin, L., Nara, H., Rahman, M., Takeda, Y., Araki, A., & Asao, H. (2018) · The Tohoku Journal of Experimental Medicine · doi:10.1620/tjem.244.187 · Cited by 3
“SHP-2 is implicated in the negative regulation of IL-6 signaling (Atsumi et al. 2002), whereas SHP-2 was reported to play a positive role in IL-3-induced activation of the ERK pathway (Yu et al.”
Negative Regulation of TH17 Differentiation
Sundrud, M. S., & Koralov, S. B. (2011) · Springer eBooks · doi:10.1007/978-1-4419-9371-7_7 · Cited by 2
Seibel, C., Pudewell, S., Rafii, P., Ettich, J., Weitz, H. T., Lang, A., Petzsch, P., Köhrer, K., Floss, D. M., & Scheller, J. (2024) · Cytokine · doi:10.1016/j.cyto.2024.156766 · Cited by 3
The gateway reflex: breaking through the blood barriers
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“Accordingly, F759 mice developed spontaneous rheumatoid arthritis‐ like joint disease and autoantibody production [58], which is consistent with the high levels of IL‐6 and clinical success of its signaling blockade in rheumatoid arthritis patients [59, 60].”
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“Studies of knock-in mice expressing a Tyr759Phe-mutated gp130 resistant to SOCS3-mediated inhibition and incapable of activating ERK1,2 demonstrated that these animals spontaneously developed an RA-like autoimmune disease, implicating IL-6 activation of STAT3 as a key mediator of the pathology (Atsumi et al., 2002).”
BackgroundKamimura, D., Arima, Y., Atsumi, T., Meng, J., Sabharwal, L., Bando, H., Ogura, H., Jiang, J., Huseby, E. S., & Murakami, M. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-800763-1.00006-3 · Cited by 1
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“The F759 mouse line carrying human gp130 (S710L) has been previously established [22].”
BackgroundImmune cell gateways in the central nervous system regulated by regional neural stimulations
Kamimura, D., Štofková, A., Nishikawa, N., Atsumi, T., Arima, Y., & Murakami, M. (2015) · Clinical and Experimental Neuroimmunology · doi:10.1111/cen3.12198 · Cited by 1
“F759 mice produce autoantibodies, show splenomegaly and spontaneously develop RA-like joint diseases as they age.(42) Furthermore, they show severe EAE, suggesting enhanced inflammatory responses.”
BackgroundSelf-citationThe Reverse-Direction Method Links Mass Experimental Data to Human Diseases
Ogura, H., Atsumi, T., Bando, H., Sabharwal, L., Yamada, M., Jiang, J.-J., Nakamura, A., Arima, Y., Kamimura, D., & Murakami, M. (2013) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.1007/s00005-013-0255-9 · Cited by 1
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Animal Models of Inflammatory Arthritis
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JAK Kinases in Leukemias, Lymphomas, and Multiple Myeloma
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“SHP-2 signal-deficient mice display splenomegaly, lymphadenopathy, and autoimmune arthritis (43, 44 ).”
BackgroundSTAT/SOCS Family Members in Inflammation and Diseases
Yoshimura, A., Kinjyo, I., Inagaki‐Ohara, K., & Hanada, T. (2003) · Springer eBooks · doi:10.1007/978-94-017-3000-6_34 · Cited by 1
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Self-citationMolecular mechanisms of biologic and targeted synthetic antirheumatic drugs in rheumatoid arthritis
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An Update Comprehensive Review on Epigenetic Modifications and Therapies in Autoimmune Diseases
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“Importantly, these mice in a mixed background with 129 and C57BL/6 spontaneously develop a rheumatoid arthritis-like autoimmune disease in old age (Atsumi et al., 2002).”
BackgroundTocilizumab: a new form of biological therapy for rheumatoid arthritis
Bálint, G., & Bálint, P. (2007) · Future Rheumatology · doi:10.2217/17460816.2.4.361
“Mice with a point mutation of tyrosine 759 in gp130 develop autoimmune arthritis through insufficient clonal selection of T cells in the thymus, and an increase in the number of autoreactive antibodies [50].”
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Experimental Models for Rheumatoid Arthritis
Holmdahl, R. (2013) · Elsevier eBooks · doi:10.1016/b978-1-4377-1738-9.00028-1
Metadata
- 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
- Life Sciences › Immunology and Microbiology › Immunology › 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
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