HMGB1 blockade attenuates experimental autoimmune myocarditis and suppresses Th17‐cell expansion
Open accessAbstract
High‐mobility group box 1 (HMGB1), a non‐histone nuclear protein, has been implicated in cardiovascular diseases. Dilated cardiomyopathy (DCM), one of the leading causes of heart failure, is often caused by coxsackievirus B3‐triggered myocarditis and promoted by the post‐infectious autoimmune process. Th17 cells, a novel CD4+ T subset, may be important in the pathogenesis of autoimmune myocarditis. In the present study, we attempted to block HMGB1 function with a monoclonal antibody specific for HMGB1 B box and investigated the effects of the blockade on Th17 cells and experimental autoimmune myocarditis (EAM). After induction of EAM, HMGB1 protein levels were significantly elevated both in the heart and blood. Administration of an anti‐HMGB1 B box mAb attenuated cardiac pathological changes and reduced the number of infiltrating inflammatory cells in the heart during EAM. These protective effects of HMGB1 blockade correlated with a reduced number of Th17 cells in local tissues and lower levels of IL‐17 in the serum. Furthermore, in vitro, studies demonstrated that HMGB1 promoted Th17‐cell expansion. Therefore, we speculate that HMGB1 blockade ameliorates cardiac pathological changes in EAM by suppressing Th17 cells.
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
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?
HMGB1 is up-regulated in heart tissue or serum in experimental autoimmune myocarditis (EAM).
“Our previous published data demonstrated that HMGB1 was up-regulated in heart tissue or serum in experimental autoimmune myocarditis (EAM);”
HMGB1 blockade ameliorates cardiac fibrosis at the last stage of EAM.
“HMGB1 blockade could efficiently ameliorate cardiac fibrosis in EAM mice.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Clustal W and Clustal X version 2.0
Larkin, M., Blackshields, G., Brown, N. P., Chenna, R., McGettigan, P., McWilliam, H., Valentin, F., Wallace, I. M., Wilm, A., López, R., et al. (2007) · Bioinformatics · doi:10.1093/bioinformatics/btm404 · Cited by 28,221 · see citing works
Korn, T., Bettelli, E., Oukka, M., & Kuchroo, V. K. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132710 · Cited by 4,873 · see citing works
CD4 T cells: fates, functions, and faults
Zhu, J., & Paul, W. E. (2008) · Blood · doi:10.1182/blood-2008-05-078154 · Cited by 1,796 · see citing works
Park, J. S., Svetkauskaite, D., He, Q., Kim, J., Strassheim, D., Ishizaka, A., & Abraham, E. H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m306793200 · Cited by 1,560 · see citing works
HMGB1 and RAGE in Inflammation and Cancer
Sims, G. P., Rowe, D. C., Rietdijk, S. T., Herbst, R., & Coyle, A. J. (2010) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132603 · Cited by 1,436 · see citing works
Andersson, U., Wang, H., Palmblad, K., Aveberger, A.-C., Bloom, O., Erlandsson-Harris, H., Janson, A., Kokkola, R., Zhang, M., Yang, H., et al. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.4.565 · Cited by 1,401 · see citing works
Steinman, L. (2007) · Nature Medicine · doi:10.1038/nm1551 · Cited by 1,367 · see citing works
Myocarditis. A histopathologic definition and classification.
Aretz, H. T., Billingham, M. E., Edwards, W. D., Factor, S. M., Fallon, J. T., Fenoglio, J. J., Olsen, E. G. J., & Schöen, F. J. (1987) · PubMed · Cited by 1,307 · see citing works
Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion
Bonaldi, T., Talamo, F., Scaffidi, P., Ferrera, D., Porto, A., Bachi, A., Rubartelli, A., Agresti, A., & Bianchi, M. E. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg516 · Cited by 1,252 · see citing works
The Receptor for Advanced Glycation End Products (RAGE) Is a Cellular Binding Site for Amphoterin
Hori, O., Brett, J., Slattery, T., Cao, R., Zhang, J., Chen, J. X., Nagashima, M., Lundh, E. R., Vijay, S., Nitecki, D., et al. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.43.25752 · Cited by 1,151 · see citing works
The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia-reperfusion
Tsung, A., Sahai, R., Tanaka, H., Nakao, A., Fink, M. P., Lotze, M. T., Yang, H., Li, J., Tracey, K. J., Geller, D. A., et al. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20042614 · Cited by 1,113 · see citing works
IL-33 and ST2 comprise a critical biomechanically induced and cardioprotective signaling system
Sanada, S., Hakuno, D., Higgins, L., Schreiter, E. R., McKenzie, A. N. J., & Lee, R. T. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30634 · Cited by 1,053 · see citing works
CD24 and Siglec-10 Selectively Repress Tissue Damage–Induced Immune Responses
Chen, G.-Y., Tang, J., Zheng, P., & Liu, Y. (2009) · Science · doi:10.1126/science.1168988 · Cited by 786 · see citing works
Self-citationHMGB1: Endogenous Danger Signaling
Klune, J. R., Dhupar, R., Cardinal, J., Billiar, T. R., & Tsung, A. (2008) · Molecular Medicine · doi:10.2119/2008-00034.klune · Cited by 762 · see citing works
HMGB1 is an endogenous immune adjuvant released by necrotic cells
Rovere, P. Q., Capobianco, A., Scaffidi, P., Valentinis, B., Catalanotti, F., Giazzon, M., Dumitriu, I. E., Müller, S., Iannacone, M., Traversari, C., et al. (2004) · EMBO Reports · doi:10.1038/sj.embor.7400205 · Cited by 591 · see citing works
The cytokine activity of HMGB1
Yang, H., Wang, H., Czura, C. J., & Tracey, K. J. (2005) · Journal of Leukocyte Biology · doi:10.1189/jlb.1104648 · Cited by 545 · see citing works
Cardiac myosin induces myocarditis in genetically predisposed mice.
Neu, N., Rose, N. R., Beisel, K. W., Herskowitz, A., Gurri-Glass, G., & Craig, S. W. (1987) · The Journal of Immunology · doi:10.4049/jimmunol.139.11.3630 · Cited by 523 · see citing works
Dumitriu, I. E., Baruah, P., Valentinis, B., Voll, R. E., Herrmann, M., Nawroth, P. P., Arnold, B., Bianchi, M. E., Manfredi, A. A., & Rovere-Querini, P. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.12.7506 · Cited by 503 · see citing works
A novel role for HMGB1 in TLR9-mediated inflammatory responses to CpG-DNA
Ivanov, S. S., Dragoi, A., Wang, X., Dallacosta, C., Louten, J., Musco, G., Sitia, G., Yap, G. S., Wan, Y., Biron, C. A., et al. (2007) · Blood · doi:10.1182/blood-2006-09-044776 · Cited by 472 · see citing works
Messmer, D., Yang, H., Telusma, G., Knoll, F., Li, J., Messmer, B., Tracey, K. J., & Chiorazzi, N. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.1.307 · Cited by 447 · see citing works
Mini‐review: The nuclear protein HMGB1 as a proinflammatory mediator
Harris, H. E., & Andersson, U. (2004) · European Journal of Immunology · doi:10.1002/eji.200424916 · Cited by 372 · see citing works
Targeting HMGB1 in inflammation
Yang, H., & Tracey, K. J. (2010) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2009.11.019 · Cited by 351 · see citing works
HMGB1: guiding immunity from within
Dumitriu, I. E., Baruah, P., Manfredi, A. A., Bianchi, M. E., & Rovere, P. Q. (2005) · Trends in Immunology · doi:10.1016/j.it.2005.04.009 · Cited by 340 · see citing works
Intestinal dendritic cells increase T cell expression of α4β7 integrin
Stagg, A. J., Kamm, M. A., & Knight, S. C. (2002) · European Journal of Immunology · doi:10.1002/1521-4141(200205)32:5 · Cited by 306 · see citing works
Hreggvidsdottir, H. S., Östberg, T., Wähämaa, H., Schierbeck, H., Aveberger, A.-C., Klevenvall, L., Palmblad, K., Ottosson, L., Andersson, U., & Harris, H. E. (2009) · Journal of Leukocyte Biology · doi:10.1189/jlb.0908548 · Cited by 289 · see citing works
Palumbo, R., Gálvez, B. G., Pusterla, T., Marchis, F. D., Cossu, G., Marcu, K. B., & Bianchi, M. E. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200704015 · Cited by 247 · see citing works
Chapter 4 Pathogenesis of Myocarditis and Dilated Cardiomyopathy
Cihakova, D., & Rose, N. R. (2008) · Advances in Immunology · doi:10.1016/s0065-2776(08)00604-4 · Cited by 223 · see citing works
Eriksson, U., Kurrer, M. O., Schmitz, N., Marsch, S. C., Fontana, A., Eugster, H.-P., & Kopf, M. (2003) · Circulation · doi:10.1161/01.cir.0000043802.38699.66 · Cited by 150 · see citing works
Interleukin‐17: A New Paradigm in Inflammation, Autoimmunity, and Therapy
Kramer, J. M., & Gaffen, S. L. (2007) · Journal of Periodontology · doi:10.1902/jop.2007.060392 · Cited by 147 · see citing works
CD11b+ Monocytes Abrogate Th17 CD4+ T Cell-Mediated Experimental Autoimmune Myocarditis
Valaperti, A., Marty, R. R., Kania, G., Germano, D., Mauermann, N., Dirnhofer, S., Leimenstoll, B. M., Błyszczuk, P., Dong, C., Mueller, C. E., et al. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.4.2686 · Cited by 137 · see citing works
Myocarditis: Infection Versus Autoimmunity
Rose, N. R. (2009) · Journal of Clinical Immunology · doi:10.1007/s10875-009-9339-z · Cited by 127 · see citing works
Miossec, P. (2007) · Arthritis & Rheumatism · doi:10.1002/art.22733 · Cited by 121 · see citing works
Role of HMGB1 in cardiovascular diseases
Li, W., Sama, A., & Wang, H. (2006) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2005.10.010 · Cited by 120 · see citing works
Shi, Y., Wang, H., Su, Z., Chen, J., Xue, Y., Wang, S., Xue, Y., He, Z., Yang, H., Zhou, C., et al. (2010) · Scandinavian Journal of Immunology · doi:10.1111/j.1365-3083.2010.02425.x · Cited by 103 · see citing works
Self-citationCD69 Limits the Severity of Cardiomyopathy After Autoimmune Myocarditis
Cruz‐Adalia, A., Jiménez‐Borreguero, L. J., Ramírez‐Huesca, M., Chico‐Calero, I., Barreiro, O., López-Conesa, E., Fresno, M., Sánchez‐Madrid, F., & Martı́n, P. (2010) · Circulation · doi:10.1161/circulationaha.110.952820 · Cited by 98 · see citing works
Postinfectious Autoimmunity: Two Distinct Phases of Coxsackievirus B3‐Induced Myocarditisa
Rose, N. R., Wolfgram, L. J., Herskowitz, A., & Beisel, K. W. (1986) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1986.tb20864.x · Cited by 95 · see citing works
Xu, H., Su, Z., Wu, J., Yang, M., Penninger, J. M., Martin, C. M., Kvietys, P. R., & Rui, T. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0902660 · Cited by 93 · see citing works
Self-citationYamashita, T., Iwakura, T., Matsui, K., Kawaguchi, H., Obana, M., Hayama, A., Maeda, M., Izumi, Y., Komuro, I., Ohsugi, Y., et al. (2011) · Cardiovascular Research · doi:10.1093/cvr/cvr148 · Cited by 88 · see citing works
Effects of HMGB1 on Ischemia-Reperfusion Injury in the Rat Heart
Oozawa, S., Mori, S., Kanke, T., Takahashi, H. K., Liu, K., Tomono, Y., Asanuma, M., Miyazaki, I., Nishibori, M., & Sano, S. (2008) · Circulation Journal · doi:10.1253/circj.72.1178 · Cited by 75 · see citing works
HMGb1 promotes scratch wound closure of HaCaT keratinocytes via ERK1/2 activation
Ranzato, E., Patrone, M., Pedrazzi, M., & Burlando, B. (2009) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-009-0192-4 · Cited by 71 · see citing works
Duan, L., Wang, C., Chen, J., Gong, Q., Zhu, P., Zheng, F., Tan, Z., Gong, F., & Fang, M. (2010) · Laboratory Investigation · doi:10.1038/labinvest.2010.141 · Cited by 68 · see citing works
Albayrak, A., Uyanik, M. H., Cerrah, S., Altaş, S., Dursun, H., Demir, M. T., & Uslu, H. (2010) · Viral Immunology · doi:10.1089/vim.2010.0080 · Cited by 63 · see citing works
The transient nature of the Th17 phenotype
Annunziato, F., & Romagnani, S. (2010) · European Journal of Immunology · doi:10.1002/eji.201041145 · Cited by 62 · see citing works
Mano, Y., Anzai, T., Kaneko, H., Nagatomo, Y., Nagai, T., Anzai, A., Maekawa, Y., Takahashi, T., Meguro, T., Yoshikawa, T., et al. (2011) · Circulation Journal · doi:10.1253/circj.cj-10-1199 · Cited by 60 · see citing works
Sensing danger—Hsp72 and HMGB1 as candidate signals
Williams, J. H. H., & Ireland, H. E. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0607356 · Cited by 51 · see citing works
Chang, H., Hanawa, H., Yoshida, T., Hayashi, M., Liu, H., Ding, L., Otaki, K., Hao, K., Yoshida, K., Kato, K., et al. (2008) · Circulation Journal · doi:10.1253/circj.72.813 · Cited by 49 · see citing works
Autoimmune heart failure: new understandings of pathogenesis
Eriksson, U., & Penninger, J. M. (2004) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2004.06.014 · Cited by 49 · see citing works
Ardoin, S. P., & Pisetsky, D. S. (2008) · Modern Rheumatology · doi:10.1007/s10165-008-0054-z · Cited by 49 · see citing works
Englert, J. M., Kliment, C. R., Ramsgaard, L., Milutinovic, P. S., Crum, L. T., Tobolewski, J. M., & Oury, T. D. (2011) · Europe PMC (PubMed Central) · Cited by 46 · see citing works
Naumnik, W., Nilklińska, W., Ossolińska, M., & Chyczewska, E. (2010) · Folia Histochemica et Cytobiologica · doi:10.2478/v10042-009-0025-z · Cited by 46 · see citing works
HMGB1 Attenuates Anti-Metastatic Defense of the Lymph Nodes in Colorectal Cancer
Moriwaka, Y., Luo, Y., Ohmori, H., Fujii, K., Tatsumoto, N., Sasahira, T., & Kuniyasu, H. (2010) · Pathobiology · doi:10.1159/000272950 · Cited by 35 · see citing works
Liu, W., Feng, W., Wang, F., et al. (2008) · Immunology and Cell Biology · doi:10.1038/icb.2008.45 · Cited by 15 · see citing works
The rag locus of Porphyromonas gingivalis might arise from Bacteroides via horizontal gene transfer
Su, Z., Kong, F., Wang, S., et al. (2010) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/s10096-010-0880-8 · Cited by 14 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 2
- [19]19. & 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2011. 41: 3586-3595 Immunomodulation
- [53]53. Sanada, S., Hakuno, D., Higgins, L. J., Schreiter, E. R., McKenzie, A. N. and Lee, R. T., IL-33 and ST2 comprise a critical biomechanically & 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2011. 41: 3586-3595
Cited by
Sorted by citations
Kang, R., Chen, R., Zhang, Q., Hou, W., Wu, S., Cao, L., Huang, J., Yu, Y., Fan, X.-G., Yan, Z., et al. (2014) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2014.05.001 · Cited by 956 · see citing works
Update on coxsackievirus B3 myocarditis
Fairweather, D., Stafford, K. A., & Sung, Y. K. (2012) · Current Opinion in Rheumatology · doi:10.1097/bor.0b013e328353372d · Cited by 165 · see citing works
Liu, Y., Zhu, H., Su, Z., Sun, C., Yin, J., Yuan, H., Sandoghchian, S., Jiao, Z., Wang, S., & Xu, H. (2012) · International Immunology · doi:10.1093/intimm/dxs056 · Cited by 110 · see citing works
Self-citationAmoah, B. P., Yang, H., Zhang, P., Su, Z., & Xu, H. (2015) · Scandinavian Journal of Immunology · doi:10.1111/sji.12298 · Cited by 41 · see citing works
Self-citationSu, Z., Yin, J., Wang, T., Sun, Y., Ni, P., Ma, R., Zhu, H., Zheng, D., Shen, H., Xu, W., et al. (2014) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12324 · Cited by 33 · see citing works
Self-citation
- Authors
- Su, Z., Sun, C., Zhou, C., Liu, Y., Zhu, H., Sandoghchian, S., Zheng, D., Peng, T., Zhang, Y., Jiao, Z., Wang, S., & Xu, H.
- Affiliations
- Jiangsu University (CN)
- Affiliated Hospital of Jiangsu University (CN)
- Peking University (CN)
- Corresponding author
- Peng, Tianqing
- Xu, Huaxi
- ORCID
- Venue
- European Journal of Immunology
- Publisher
- Wiley
- Published
- 2011-11-10
- Volume
- 41
- Issue
- 12
- Pages
- 3586-3595
- ISSN
- 0014-2980 (ISSN-L)
- 1521-4141
- OpenAlex
- W2038063394
- Semantic Scholar
- d1acad01b61156e29cae35ffca55cd977431cd4b
- Cited by
- 81
- References
- 55
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 5 · 2023: 1 · 2022: 2 · 2021: 4 · 2020: 7 · 2019: 6 · 2018: 7 · 2017: 7 · 2016: 5 · 2015: 7 · 2014: 7 · 2013: 10 · 2012: 6
- FWCI
- 5.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (30972748, 09KJB310001, CX09B_217Z, 81001319)
- Government of Jiangsu Province
- Natural Science Research of Jiangsu Higher Education Institutions of China
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Keywords
- HMGB1, experimental autoimmune myocarditis, Th17 cells, IL-17, anti-HMGB1 monoclonal antibody, dilated cardiomyopathy, coxsackievirus B3, autoimmunity, cardiac inflammation
- MeSH terms
- Animals, Antibodies, Monoclonal, Autoimmune Diseases, Mice, Inbred BALB C, Myocarditis, Myocardium, Up-Regulation, Interleukin-17, HMGB1 Protein, Mice, Th17 Cells
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
