{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T16:49:03Z","timestamp":1776876543048,"version":"3.51.2"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,11,23]],"date-time":"2015-11-23T00:00:00Z","timestamp":1448236800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,11,23]],"date-time":"2015-11-23T00:00:00Z","timestamp":1448236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Autoantibodies against the M<jats:sub>2<\/jats:sub> receptors (M<jats:sub>2<\/jats:sub>AChR) have been associated with Dilated Cardiomyopathy (DCM). In the heart, P2\u00d77 receptors influence electrical conduction, coronary circulation and response to ischemia. They can also trigger pro-inflammatory responses and the development of neurological, cardiac and renal disorders. Here, P2\u00d77<jats:sup>\u2212\/\u2212<\/jats:sup> mice displayed an increased heart rate and ST segment depression, but similar exercise performance when compared to wild type (WT) animals. After immunization with plasmid containing M<jats:sub>2<\/jats:sub>AChR cDNA sequence, WT mice produced anti-M<jats:sub>2<\/jats:sub>AChR antibodies, while P2\u00d77<jats:sup>\u2212\/\u2212<\/jats:sup> mice showed an attenuated production. Despite this, WT and P2\u00d77<jats:sup>\u2212\/\u2212<\/jats:sup> showed left ventricle cavity enlargement and decreased exercise tolerance. Transfer of serum from M<jats:sub>2<\/jats:sub>AChR WT immunized mice to n\u00e4ive recipients led to an alteration in heart shape. P2\u00d77<jats:sup>\u2212\/\u2212<\/jats:sup> mice displayed a significant increase in the frequency of spleen regulatory T cells population, which is mainly composed by the FoxP3<jats:sup>+<\/jats:sup>CD25<jats:sup>\u2212<\/jats:sup> subset. M<jats:sub>2<\/jats:sub>AChR WT immunized mice showed an increase in IL-1\u03b2, IFN\u03b3 and IL-17 levels in the heart, while P2\u00d77<jats:sup>\u2212\/\u2212<\/jats:sup> group produced lower amounts of IL-1\u03b2 and IL-17 and higher amounts of IFN\u03b3. These results pointed to previously unnoticed roles of P2\u00d77 in cardiovascular and immune systems and underscored the participation of IL-17 and IFN\u03b3 in the progress of autoimmune DCM.<\/jats:p>","DOI":"10.1038\/srep16940","type":"journal-article","created":{"date-parts":[[2015,11,23]],"date-time":"2015-11-23T10:02:15Z","timestamp":1448272935000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["P2\u00d77 purinergic signaling in dilated cardiomyopathy induced by auto-immunity against muscarinic M2 receptors: autoantibody levels, heart functionality and cytokine expression"],"prefix":"10.1038","volume":"5","author":[{"given":"Camila Guerra","family":"Martinez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Zamith-Miranda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcia Gracindo","family":"da Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karla Consort","family":"Ribeiro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iza\u00edra Trincani","family":"Brand\u00e3o","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Celio Lopes","family":"Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno Louren\u00e7o","family":"Diaz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Bellio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro Muanis","family":"Persechini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleonora","family":"Kurtenbach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,11,23]]},"reference":[{"key":"BFsrep16940_CR1","doi-asserted-by":"crossref","first-page":"478","DOI":"10.4330\/wjc.v6.i6.478","volume":"26","author":"H Sisakian","year":"2014","unstructured":"Sisakian, H. Cardiomyopathies: Evolution of pathogenesis concepts and potencial for new therapies. Worl J Cardiol 26, 478\u2013494 (2014).","journal-title":"Worl J Cardiol"},{"key":"BFsrep16940_CR2","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.pcad.2014.03.003","volume":"57","author":"K Modesto","year":"2014","unstructured":"Modesto, K. & Sengupta, P. P. Myocardial mechanics in cardiomyopathies. Prog Cardiovasc Dis 57, 111\u2013124 (2014).","journal-title":"Prog Cardiovasc Dis"},{"key":"BFsrep16940_CR3","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1172\/JCI116416","volume":"91","author":"LX Fu","year":"1993","unstructured":"Fu, L. X. et al. Localization of a functional autoimmune epitope on the muscarinic acetylcholine receptor-2 in patients with idiopathic dilated cardiomyopathy. J Clin Invest 91, 1964\u20131968 (1993).","journal-title":"J Clin Invest"},{"key":"BFsrep16940_CR4","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1161\/01.CIR.96.6.2031","volume":"96","author":"SF de Oliveira","year":"1997","unstructured":"de Oliveira, S. F., Pedrosa, R. C., Nascimento, J. H. M., de Carvalho, A. C. C. & Masuda, M. O. Sera from chronic chagasic patients with complex cardiac arrhythmias depress electrogenesis and conduction in isolated rabbit hearts. Circulation 96, 2031\u20132037 (1997).","journal-title":"Circulation"},{"key":"BFsrep16940_CR5","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1096\/fasebj.11.1.9034169","volume":"11","author":"J Goin","year":"1997","unstructured":"Goin, J., Leiros, C. P., Borda, E. & Sterin-Borda, L. Interaction of human chagasic IgG with the second extracellular loop of the human heart muscarinic acetylcholine receptor: functional and pathological implications. FASEB J 11, 77\u201383 (1997).","journal-title":"FASEB J"},{"key":"BFsrep16940_CR6","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1096\/fj.04-3042com","volume":"19","author":"J-C Peter","year":"2005","unstructured":"Peter, J.-C. et al. Effects on heart rate of an anti-M2 acetylcholine receptor immune response in mice. FASEB J 19, 943\u2013949 (2005).","journal-title":"FASEB J"},{"key":"BFsrep16940_CR7","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1016\/j.ehj.2004.05.012","volume":"25","author":"A Baba","year":"2004","unstructured":"Baba, A. et al. Autoantibodies against M2-muscarinic acetylcholine receptors: new upstream targets in atrial fibrillation in patients with dilated cardiomyopathy. Eur Heart J 25, 1108\u20131115 (2004).","journal-title":"Eur Heart J"},{"key":"BFsrep16940_CR8","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/nri3800","volume":"15","author":"S Epelman","year":"2015","unstructured":"Epelman, S., Liu, P. P. & Mann, D. L. Role of innate and adaptive immune mechanisms in cardiac injury and repair. Nat Rev Immunol 15, 117\u2013129 (2015).","journal-title":"Nat Rev Immunol"},{"key":"BFsrep16940_CR9","doi-asserted-by":"crossref","first-page":"e15531","DOI":"10.1371\/journal.pone.0015531","volume":"5","author":"HS Domingues","year":"2010","unstructured":"Domingues, H. S., Mues, M., Lassmann, H., Wekerle, H. & Krishnamoorthy, G. Functional and pathogenic differences of Th1 and Th17 cells in experimental autoimmune encephalomyelitis. PloS One 5, e15531 (2010).","journal-title":"PloS One"},{"key":"BFsrep16940_CR10","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1084\/jem.20071258","volume":"205","author":"D Luger","year":"2008","unstructured":"Luger, D. et al. Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category. J Exp Med 205, 799\u2013810 (2008).","journal-title":"J Exp Med"},{"key":"BFsrep16940_CR11","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1111\/j.1749-6632.2009.05133.x","volume":"1183","author":"JM Damsker","year":"2010","unstructured":"Damsker, J. M., Hansen, A. M. & Caspi, R. R. Th1 and Th17 cells. Ann N Y Acad Sci 1183, 211\u2013221 (2010).","journal-title":"Ann N Y Acad Sci"},{"key":"BFsrep16940_CR12","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.immuni.2008.11.005","volume":"30","author":"YK Lee","year":"2009","unstructured":"Lee, Y. K. et al. Late developmental plasticity in the T helper 17 lineage. Immunity 30, 92\u2013107 (2009).","journal-title":"Immunity"},{"key":"BFsrep16940_CR13","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.immuni.2014.01.002","volume":"40","author":"Y Wang","year":"2014","unstructured":"Wang, Y. et al. The Transcription Factors T-bet and Runx Are Required for the Ontogeny of Pathogenic Interferon-\u03b3-Producing T Helper 17 Cells. Immunity 40, 355\u2013366 (2014).","journal-title":"Immunity"},{"key":"BFsrep16940_CR14","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1161\/CIRCRESAHA.109.213157","volume":"06","author":"GC Baldeviano","year":"2010","unstructured":"Baldeviano, G. C. et al. Interleukin-17A is dispensable for myocarditis but essential for the progression to dilated cardiomyopathy. Circ Res 06, 1646\u20131655 (2010).","journal-title":"Circ Res"},{"key":"BFsrep16940_CR15","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1084\/jem.20132126","volume":"211","author":"L Wu","year":"2014","unstructured":"Wu, L. et al. Cardiac fibroblasts mediate IL-17A\u2013driven inflammatory dilated cardiomyopathy. J Exp Med 211, 1449\u20131464 (2014).","journal-title":"J Exp Med"},{"key":"BFsrep16940_CR16","doi-asserted-by":"crossref","first-page":"4038","DOI":"10.4049\/jimmunol.1301282","volume":"191","author":"JG Barin","year":"2013","unstructured":"Barin, J. G. et al. Fatal eosinophilic myocarditis develops in the absence of IFN-\u03b3 and IL-17A. J Immunol 191, 4038\u20134047 (2013).","journal-title":"J Immunol"},{"key":"BFsrep16940_CR17","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1073\/pnas.0408241102","volume":"102","author":"M Afanasyeva","year":"2005","unstructured":"Afanasyeva, M. et al. Impaired up-regulation of CD25 on CD4+ T cells in IFN-\u03b3 knockout mice is associated with progression of myocarditis to heart failure. Proc Natl Acad Sci USA 102, 180\u2013185 (2005).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep16940_CR18","first-page":"1","volume":"2014","author":"LG Nogueira","year":"2014","unstructured":"Nogueira, L. G. et al. Myocardial gene expression of T-bet, GATA-3, Ror-t, FoxP3 and hallmark cytokines in chronic chagas disease cardiomyopathy: an essentially unopposed T H 1-type response. Mediators Inflamm 2014, 1\u20139 (2014).","journal-title":"Mediators Inflamm"},{"key":"BFsrep16940_CR19","doi-asserted-by":"crossref","first-page":"e1004594","DOI":"10.1371\/journal.ppat.1004594","volume":"11","author":"IR Pereira","year":"2015","unstructured":"Pereira, I. R. et al. A human type 5 adenovirus-based Trypanosoma cruzi therapeutic vaccine re-programs immune response and reverses chronic cardiomyopathy. PLoS Pathog 11, e1004594 (2015).","journal-title":"PLoS Pathog"},{"key":"BFsrep16940_CR20","doi-asserted-by":"crossref","first-page":"e604","DOI":"10.1371\/journal.pntd.0000604","volume":"4","author":"PM da Matta Guedes","year":"2010","unstructured":"da Matta Guedes, P. M. et al. IL-17 produced during Trypanosoma cruzi infection plays a central role in regulating parasite-induced myocarditis. PLoS Negl Trop Dis 4, e604 (2010).","journal-title":"PLoS Negl Trop Dis"},{"key":"BFsrep16940_CR21","doi-asserted-by":"crossref","first-page":"e1630","DOI":"10.1371\/journal.pntd.0001630","volume":"6","author":"PMM Guedes","year":"2012","unstructured":"Guedes, P. M. M. et al. Deficient regulatory T cell activity and low frequency of IL-17-producing T cells correlate with the extent of cardiomyopathy in human chagas\u2019 disease. PLoS Negl Trop Dis 6, e1630 (2012).","journal-title":"PLoS Negl Trop Dis"},{"key":"BFsrep16940_CR22","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.yjmcc.2004.12.009","volume":"38","author":"LE Gim\u00e9nez","year":"2005","unstructured":"Gim\u00e9nez, L. E. et al. DNA immunizations with M2 muscarinic and \u03b21 adrenergic receptor coding plasmids impair cardiac function in mice. J Mol Cell Cardiol 38, 703\u2013714 (2005).","journal-title":"J Mol Cell Cardiol"},{"key":"BFsrep16940_CR23","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.cell.2014.04.007","volume":"157","author":"M Lamkanfi","year":"2014","unstructured":"Lamkanfi, M. & Dixit, V. M. Mechanisms and functions of inflammasomes. Cell 157, 1013\u20131022 (2014).","journal-title":"Cell"},{"key":"BFsrep16940_CR24","doi-asserted-by":"crossref","first-page":"63","DOI":"10.2302\/kjm.2013-0003-RE","volume":"62","author":"G Burnstock","year":"2013","unstructured":"Burnstock, G. Purinergic signalling: pathophysiology and therapeutic potential. Keio J Med 62, 63\u201373 (2013).","journal-title":"Keio J Med"},{"key":"BFsrep16940_CR25","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1016\/j.micinf.2012.07.006","volume":"14","author":"A Rayah","year":"2012","unstructured":"Rayah, A., Kanellopoulos, J. M. & Di Virgilio, F. P2 receptors and immunity. Microbes Infect 14, 1254\u20131262 (2012).","journal-title":"Microbes Infect"},{"key":"BFsrep16940_CR26","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1038\/nm.2028","volume":"15","author":"F Ghiringhelli","year":"2009","unstructured":"Ghiringhelli, F. et al. Activation of the NLRP3 inflammasome in dendritic cells induces IL-1\u03b2\u2013dependent adaptive immunity against tumors. Nat Med 15, 1170\u20131178 (2009).","journal-title":"Nat Med"},{"key":"BFsrep16940_CR27","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/ni.2514","volume":"14","author":"IK Pang","year":"2013","unstructured":"Pang, I. K., Ichinohe, T. & Iwasaki, A. IL-1R signaling in dendritic cells replaces pattern-recognition receptors in promoting CD8+ T cell responses to influenza A virus. Nat Immunol 14, 246\u2013253 (2013).","journal-title":"Nat Immunol"},{"key":"BFsrep16940_CR28","first-page":"107","volume":"34","author":"B Rissiek","year":"2015","unstructured":"Rissiek, B., Haag, F., Boyer, O., Koch-Nolte, F. & Adriouch, S. ADP-Ribosylation of P2\u00d77: a matter of life and death for regulatory T cells and natural killer T cells. Curr Top Microbiol Immunol 34, 107\u2013126 (2015).","journal-title":"Curr Top Microbiol Immunol"},{"key":"BFsrep16940_CR29","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1007\/s00380-014-0527-2","volume":"30","author":"H Zempo","year":"2014","unstructured":"Zempo, H. et al. A P2X7 receptor antagonist attenuates experimental autoimmune myocarditis via suppressed myocardial CD4+ T and macrophage infiltration and NADPH oxidase 2\/4 expression in mice. Heart Vessels, 30, 527\u2013533 (2014).","journal-title":"Heart Vessels"},{"key":"BFsrep16940_CR30","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.vph.2015.06.003","volume":"73","author":"M Granado","year":"2015","unstructured":"Granado, M. et al. Altered expression of P2Y2 and P2\u00d77 purinergic receptors in the isolated rat heart mediates ischemia\u2013reperfusion injury. Vascul Pharmacol, 73, 96\u2013103 (2015).","journal-title":"Vascul Pharmacol"},{"key":"BFsrep16940_CR31","doi-asserted-by":"crossref","first-page":"H881","DOI":"10.1152\/ajpheart.00305.2011","volume":"301","author":"DA Vessey","year":"2011","unstructured":"Vessey, D. A., Li, L. & Kelley, M. P2\u00d77 receptor agonists pre-and postcondition the heart against ischemia-reperfusion injury by opening pannexin-1\/P2\u00d77 channels. Am J Physiol Heart Circ Physiol 301, H881\u2013H887 (2011).","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"BFsrep16940_CR32","doi-asserted-by":"crossref","first-page":"19725","DOI":"10.1073\/pnas.1108586108","volume":"108","author":"E Mezzaroma","year":"2011","unstructured":"Mezzaroma, E. et al. The inflammasome promotes adverse cardiac remodeling following acute myocardial infarction in the mouse. Proc Natl Acad Sci 108, 19725\u201319730 (2011).","journal-title":"Proc Natl Acad Sci"},{"key":"BFsrep16940_CR33","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1152\/physrev.00012.2007","volume":"87","author":"FG Spinale","year":"2007","unstructured":"Spinale, F. G. Myocardial matrix remodeling and the matrix metalloproteinases: influence on cardiac form and function. Physiol Rev 87, 1285\u20131342 (2007).","journal-title":"Physiol Rev"},{"key":"BFsrep16940_CR34","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/ni904","volume":"4","author":"JD Fontenot","year":"2003","unstructured":"Fontenot, J. D., Gavin, M. A. & Rudensky, A. Y. Foxp3 programs the development and function of CD4+ CD25+ regulatory T cells. Nat Immunol 4, 330\u2013336 (2003).","journal-title":"Nat Immunol"},{"key":"BFsrep16940_CR35","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1111\/imr.12175","volume":"259","author":"S Hori","year":"2014","unstructured":"Hori, S. Lineage stability and phenotypic plasticity of Foxp3+ regulatory T cells. Immunol Rev 259, 159\u2013172 (2014).","journal-title":"Immunol Rev"},{"key":"BFsrep16940_CR36","doi-asserted-by":"crossref","first-page":"e1002212","DOI":"10.1371\/journal.ppat.1002212","volume":"7","author":"CM Miller","year":"2011","unstructured":"Miller, C. M. et al. The role of the P2\u00d77 receptor in infectious diseases. PLoS Pathog 7, e1002212 (2011).","journal-title":"PLoS Pathog"},{"key":"BFsrep16940_CR37","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.4049\/jimmunol.163.4.1958","volume":"163","author":"C Mutini","year":"1999","unstructured":"Mutini, C. et al. Mouse dendritic cells express the P2\u00d77 purinergic receptor: characterization and possible participation in antigen presentation. JImmunol 163, 1958 (1999).","journal-title":"JImmunol"},{"key":"BFsrep16940_CR38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11897-014-0217-5","volume":"11","author":"Y Nagatomo","year":"2014","unstructured":"Nagatomo, Y. & Tang, W. W. Autoantibodies and Cardiovascular Dysfunction: Cause or Consequence? Curr Heart Fail Rep 11, 1\u20139 (2014).","journal-title":"Curr Heart Fail Rep"},{"key":"BFsrep16940_CR39","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s00418-010-0716-8","volume":"134","author":"K Barth","year":"2010","unstructured":"Barth, K. et al. Increased P2X7R expression in atrial cardiomyocytes of caveolin-1 deficient mice. Histochem Cell Biol 134, 31\u201338 (2010).","journal-title":"Histochem Cell Biol"},{"key":"BFsrep16940_CR40","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1007\/s00210-009-0403-2","volume":"379","author":"H Musa","year":"2009","unstructured":"Musa, H. et al. P2 purinergic receptor mRNA in rat and human sinoatrial node and other heart regions. Naunyn Schmiedebergs Arch Pharmacol 379, 541\u2013549 (2009).","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"BFsrep16940_CR41","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1097\/FJC.0b013e3181e0f8b2","volume":"56","author":"A Pelleg","year":"2010","unstructured":"Pelleg, A. & Belhassen, B. The Mechanism of the Negative Chronotropic and Dromotropic Actions of Adenosine 5\u2032-triphosphate in the Heart: An Update. J Cardiovasc Pharmacol 56, 106\u2013109 (2010).","journal-title":"J Cardiovasc Pharmacol"},{"key":"BFsrep16940_CR42","doi-asserted-by":"crossref","first-page":"404","DOI":"10.3949\/ccjm.78a.10077","volume":"78","author":"EB Hanna","year":"2011","unstructured":"Hanna, E. B. & Glancy, D. L. ST-segment depression and T-wave inversion: classification, differential diagnosis and caveats. Cleve Clin J Med 78, 404\u2013414 (2011).","journal-title":"Cleve Clin J Med"},{"key":"BFsrep16940_CR43","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.cardiores.2003.10.026","volume":"61","author":"A Deten","year":"2004","unstructured":"Deten, A. et al. Norepinephrine-induced acute heart failure in transgenic mice overexpressing erythropoietin. Cardiovasc Res 61, 105\u2013114 (2004).","journal-title":"Cardiovasc Res"},{"key":"BFsrep16940_CR44","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1111\/j.1365-2249.2012.04598.x","volume":"169","author":"P Chen","year":"2012","unstructured":"Chen, P. et al. Susceptibility to autoimmune myocarditis is associated with intrinsic differences in CD4+ T cells. Clin Exp Immunol 169, 79\u201388 (2012).","journal-title":"Clin Exp Immunol"},{"key":"BFsrep16940_CR45","doi-asserted-by":"crossref","first-page":"ra12","DOI":"10.1126\/scisignal.2001270","volume":"4","author":"U Schenk","year":"2011","unstructured":"Schenk, U. et al. ATP inhibits the generation and function of regulatory T cells through the activation of purinergic P2X receptors. Sci Signal 4, ra12 (2011).","journal-title":"Sci Signal"},{"key":"BFsrep16940_CR46","first-page":"1","volume":"2","author":"M Bonelli","year":"2014","unstructured":"Bonelli, M. et al. CD4 CD25\u2212 Foxp3 T cells: a marker for lupus nephritis? Arthrit Res Ther 2, 1\u201311 (2014).","journal-title":"Arthrit Res Ther"},{"key":"BFsrep16940_CR47","doi-asserted-by":"crossref","first-page":"R153","DOI":"10.1186\/ar2829","volume":"11","author":"H Yang","year":"2009","unstructured":"Yang, H. et al. Are CD4+ CD25-Foxp3+ cells in untreated new-onset lupus patients regulatory T cells. Arthritis Res Ther 11, R153 (2009).","journal-title":"Arthritis Res Ther"},{"key":"BFsrep16940_CR48","doi-asserted-by":"crossref","first-page":"4091","DOI":"10.1073\/pnas.0408679102","volume":"102","author":"S Zelenay","year":"2005","unstructured":"Zelenay, S. et al. Foxp3+ CD25\u2013CD4 T cells constitute a reservoir of committed regulatory cells that regain CD25 expression upon homeostatic expansion. Proc Natl Acad Sci USA 102, 4091\u20134096 (2005).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep16940_CR49","doi-asserted-by":"crossref","unstructured":"Z\u00f3ka, A. et al. Extension of the CD4+ Foxp3+ CD25(low) regulatory T-cell subpopulation in type 1 diabetes mellitus. Autoimmunity, 1\u20139 (2014).","DOI":"10.3109\/08916934.2014.992518"},{"key":"BFsrep16940_CR50","doi-asserted-by":"crossref","first-page":"e1002658","DOI":"10.1371\/journal.ppat.1002658","volume":"8","author":"JT Boari","year":"2012","unstructured":"Boari, J. T. et al. IL-17RA signaling reduces inflammation and mortality during Trypanosoma cruzi infection by recruiting suppressive IL-10-producing neutrophils. PLoS Pathog 8, e1002658 (2012).","journal-title":"PLoS Pathog"},{"key":"BFsrep16940_CR51","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.immuni.2009.02.007","volume":"30","author":"Y Chung","year":"2009","unstructured":"Chung, Y. et al. Critical regulation of early Th17 cell differentiation by interleukin-1 signaling. Immunity 30, 576\u2013587 (2009).","journal-title":"Immunity"},{"key":"BFsrep16940_CR52","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1084\/jem.20060285","volume":"203","author":"C Sutton","year":"2006","unstructured":"Sutton, C., Brereton, C., Keogh, B., Mills, K. H. & Lavelle, E. C. A crucial role for interleukin IL-1 in the induction of IL-17 - producing T cells that mediate autoimmune encephalomyelitis. J Exp Med 203, 1685\u20131691 (2006).","journal-title":"J Exp Med"},{"key":"BFsrep16940_CR53","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1128\/CVI.00032-12","volume":"20","author":"CE Rosas-Jorquera","year":"2013","unstructured":"Rosas-Jorquera, C. E. et al. Challenge of Chronically Infected Mice with Homologous Trypanosoma cruzi Parasites Enhances the Immune Response but Does Not Modify Cardiopathy: Implications for the Design of a Therapeutic Vaccine. Clin Vaccine Immunol 20, 248\u2013254 (2013).","journal-title":"Clin Vaccine Immunol"},{"key":"BFsrep16940_CR54","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1016\/j.ajpath.2012.08.040","volume":"181","author":"PF Cosper","year":"2012","unstructured":"Cosper, P. F., Harvey, P. A. & Leinwand, L. A. Interferon-\u03b3 causes cardiac myocyte atrophy via selective degradation of myosin heavy chain in a model of chronic myocarditis. Am J Pathol 181, 2038\u20132046 (2012).","journal-title":"Am J Pathol"},{"key":"BFsrep16940_CR55","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1161\/CIRCHEARTFAILURE.113.000604","volume":"7","author":"K Savvatis","year":"2014","unstructured":"Savvatis, K. et al. Interleukin-23 deficiency leads to impaired wound healing and adverse prognosis after myocardial infarction. Circ Heart Fail 7, 161\u2013171 (2014).","journal-title":"Circ Heart Fail"},{"key":"BFsrep16940_CR56","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.ajpath.2011.09.006","volume":"180","author":"M Torzewski","year":"2012","unstructured":"Torzewski, M. et al. Chronic inflammatory cardiomyopathy of interferon \u03b3\u2013overexpressing transgenic mice Is mediated by tumor necrosis factor-\u03b1. Am J Pathol 180, 73\u201381 (2012).","journal-title":"Am J Pathol"},{"key":"BFsrep16940_CR57","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1038\/nm960","volume":"9","author":"U Eriksson","year":"2003","unstructured":"Eriksson, U. et al. Dendritic cell\u2013induced autoimmune heart failure requires cooperation between adaptive and innate immunity. Nat Med 9, 1484\u20131490 (2003).","journal-title":"Nat Med"},{"key":"BFsrep16940_CR58","doi-asserted-by":"crossref","first-page":"3210","DOI":"10.1074\/jbc.M104388200","volume":"277","author":"RA Le Feuvre","year":"2002","unstructured":"Le Feuvre, R. A., Brough, D., Iwakura, Y., Takeda, K. & Rothwell, N. J. Priming of macrophages with lipopolysaccharide potentiates P2X7-mediated cell death via a caspase-1-dependent mechanism, independently of cytokine production. J Biol Chem 277, 3210\u20133218 (2002).","journal-title":"J Biol Chem"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep16940.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep16940","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep16940.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T18:43:41Z","timestamp":1672944221000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep16940"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,11,23]]},"references-count":58,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2015,12,22]]}},"alternative-id":["BFsrep16940"],"URL":"https:\/\/doi.org\/10.1038\/srep16940","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,11,23]]},"assertion":[{"value":"26 August 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 October 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 November 2015","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"16940"}}