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Viral infection remains the main cause of myocarditis. Noninfectious forms include lymphocytic, eosinophilic, giant cell, cardiac sarcoidosis, and immune checkpoint inhibitor\u2010associated myocarditis. Prognosis worsens with left ventricular dysfunction, heart failure, or malignant arrhythmias, yet the determinants of recovery versus progression to dilated cardiomyopathy (DCM) remain uncertain. This review integrates human studies with mechanistic models to map convergent pathways that connect pattern\u2010recognition signaling, antigen presentation, and T\u2010 and B\u2010cell responses with monocyte and macrophage networks that drive injury, fibrosis, and electrical instability. Across etiologies, \u03b1\u2010myosin heavy chain (\u03b1\u2010MyHC) reactive T cells recur as key effectors. We advance a unifying model in which cardiac tissue\u2010resident memory T cells (TRMs) specific for myosin persist in health but ignite disease when tolerance is breached by infection, injury, or checkpoint blockade. We appraise coxsackievirus B3 (CVB3) infection, experimental autoimmune myocarditis (EAM), and checkpoint perturbation systems that capture patient heterogeneity and enable tracking of antigen\u2010specific responses. Building on these insights, we outline priorities for biomarker\u2010guided endotyping, imaging\u2013omics integration, and targeted immunomodulation that limits progression to inflammatory cardiomyopathy while preserving protective tissue immunity and, in ICI settings, antitumor immunity.<\/jats:p>","DOI":"10.1111\/imr.70111","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T04:16:11Z","timestamp":1771560971000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Immune Mechanisms of Viral, Autoimmune, and Immune Checkpoint Inhibitor\u2010Associated Myocarditis"],"prefix":"10.1111","volume":"338","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2392-900X","authenticated-orcid":false,"given":"Wonyoung","family":"Jo","sequence":"first","affiliation":[{"name":"Department of Pathology Johns Hopkins University, School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian","family":"Sun","sequence":"additional","affiliation":[{"name":"W. Harry Feinstone Department of Molecular Microbiology and Immunology Johns Hopkins University, Bloomberg School of Public Health  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8713-2860","authenticated-orcid":false,"given":"Daniela","family":"\u010cih\u00e1kov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Pathology Johns Hopkins University, School of Medicine  Baltimore Maryland USA"},{"name":"W. Harry Feinstone Department of Molecular Microbiology and Immunology Johns Hopkins University, Bloomberg School of Public Health  Baltimore Maryland 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