{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T06:47:00Z","timestamp":1784875620067,"version":"3.55.0"},"reference-count":26,"publisher":"American Physiological Society","issue":"1","funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["CDA24110032"],"award-info":[{"award-number":["CDA24110032"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["F32HL127958"],"award-info":[{"award-number":["F32HL127958"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL122309"],"award-info":[{"award-number":["R01HL122309"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2020,1,1]]},"abstract":"<jats:p> In humans, loss of central tolerance for the cardiac self-antigen \u03b1-myosin heavy chain (\u03b1-MHC) leads to circulation of cardiac autoreactive T cells and renders the heart susceptible to autoimmune attack after acute myocardial infarction (MI). MI triggers profound tissue damage, releasing danger signals and self-antigen by necrotic cardiomyocytes, which lead to recruitment of inflammatory monocytes. We hypothesized that excessive inflammation by monocytes contributes to the initiation of adaptive immune responses to cardiac self-antigen. Using an experimental model of MI in \u03b1-MHC-mCherry reporter mice, which specifically express mCherry in cardiomyocytes, we detected \u03b1-MHC antigen in myeloid cells in the heart-draining mediastinal lymph node (MLN) 7 days after MI. To test whether monocytes were required for cardiac self-antigen trafficking to the MLN, we blocked monocyte recruitment with a C-C motif chemokine receptor type 2 (CCR2) antagonist or immune modifying nanoparticles (IMP). Blockade of monocyte recruitment reduced \u03b1-MHC antigen detection in the MLN after MI. Intramyocardial injection of the model antigen ovalbumin into OT-II transgenic mice demonstrated the requirement for monocytes in antigen trafficking and T-cell activation in the MLN. Finally, in nonobese diabetic mice, which are prone to postinfarction autoimmunity, blockade of monocyte recruitment reduced \u03b1-MHC-specific responses leading to improved tissue repair and ventricular function 28 days after MI. Taken together, these data support a role for monocytes in the onset of pathological cardiac autoimmunity following MI and suggest that therapeutic targeting of monocytes may mitigate postinfarction autoimmunity in humans. <\/jats:p><jats:p> NEW &amp; NOTEWORTHY Our study newly identifies a role for inflammatory monocytes in priming an autoimmune T-cell response after myocardial infarction. Select inhibition of monocyte recruitment to the infarct prevents trafficking of cardiac self-antigen and activation of cardiac myosin reactive T cells in the heart-draining lymph node. Therapeutic targeting of inflammatory monocytes may limit autoimmune responses to improve cardiac remodeling and preserve left ventricular function after myocardial infarction. <\/jats:p>","DOI":"10.1152\/ajpheart.00595.2019","type":"journal-article","created":{"date-parts":[[2019,12,6]],"date-time":"2019-12-06T13:28:54Z","timestamp":1575638934000},"page":"H116-H123","source":"Crossref","is-referenced-by-count":27,"title":["Monocytes prime autoreactive T cells after myocardial infarction"],"prefix":"10.1152","volume":"318","author":[{"given":"Matthew","family":"DeBerge","sequence":"first","affiliation":[{"name":"Department of Pathology, Northwestern University, Chicago, Illinois"},{"name":"Feinberg Cardiovascular and Renal Research Institute, Northwestern University, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangjin","family":"Yu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Duke University, 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