{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T17:14:26Z","timestamp":1793726066133,"version":"4.6.1"},"reference-count":43,"publisher":"American Society for Clinical Investigation","issue":"11","funder":[{"name":"nih","award":["T32 HL007081"],"award-info":[{"award-number":["T32 HL007081"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,6,7]]},"abstract":"<jats:p>\n                    Despite the long-standing recognition that the immune response to acute myocardial injury contributes to adverse left ventricular (LV) remodeling, it has not been possible to effectively target this clinically. Using 2 different in vivo models of acute myocardial injury, we show that pirfenidone confers beneficial effects in the murine heart through an unexpected mechanism that depends on cardiac B lymphocytes. Naive hearts contained a large population of CD19\n                    <jats:sup>+<\/jats:sup>\n                    CD11b\n                    <jats:sup>\u2013<\/jats:sup>\n                    CD23\n                    <jats:sup>\u2013<\/jats:sup>\n                    CD21\n                    <jats:sup>\u2013<\/jats:sup>\n                    IgD\n                    <jats:sup>+<\/jats:sup>\n                    IgM\n                    <jats:sup>lo<\/jats:sup>\n                    lymphocytes, and 2 smaller populations of CD19\n                    <jats:sup>+<\/jats:sup>\n                    CD11b\n                    <jats:sup>+<\/jats:sup>\n                    B1a and B1b cells. In response to tissue injury, there was an increase in neutrophils, monocytes, macrophages, as well as an increase in CD19\n                    <jats:sup>+<\/jats:sup>\n                    CD11b\n                    <jats:sup>\u2013<\/jats:sup>\n                    B lymphocytes. Treatment with pirfenidone had no effect on the number of neutrophils, monocytes, or macrophages, but decreased CD19\n                    <jats:sup>+<\/jats:sup>\n                    CD11b\n                    <jats:sup>\u2013<\/jats:sup>\n                    lymphocytes. B cell depletion abrogated the beneficial effects of pirfenidone. In vitro studies demonstrated that stimulation with lipopolysaccharide and extracts from necrotic cells activated CD19\n                    <jats:sup>+<\/jats:sup>\n                    lymphocytes through a\n                    <jats:italic>TIRAP<\/jats:italic>\n                    -dependent pathway. Treatment with pirfenidone attenuated this activation of B cells. These findings reveal a previously unappreciated complexity of myocardial B lymphocytes within the inflammatory infiltrate triggered by cardiac injury and suggest that pirfenidone exerts beneficial effects in the heart through a unique mechanism that involves modulation of cardiac B lymphocytes.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.120137","type":"journal-article","created":{"date-parts":[[2018,6,6]],"date-time":"2018-06-06T11:01:10Z","timestamp":1528282870000},"source":"Crossref","is-referenced-by-count":85,"title":["Modulation of subsets of cardiac B lymphocytes improves cardiac function after acute injury"],"prefix":"10.1172","volume":"3","author":[{"given":"Luigi","family":"Adamo","sequence":"first","affiliation":[{"name":"Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lora 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