Modulation of subsets of cardiac B lymphocytes improves cardiac function after acute injury
Staloch, Lora J
Matkovich, Scot J
Weinheimer, Carla J
Schilling, Joel D
Barger, Philip M
Mann, Douglas L
AffiliationUniv Arizona, Dept Immunobiol
MetadataShow full item record
PublisherAMER SOC CLINICAL INVESTIGATION INC
CitationJCI Insight. 2018;3(11):e120137. https://doi.org/10.1172/jci.insight.120137.
RightsCopyright © 2018, American Society for Clinical Investigation.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at email@example.com.
AbstractDespite 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+CD11b–CD23–CD21–IgD+IgMlo lymphocytes, and 2 smaller populations of CD19+CD11b+ B1a and B1b cells. In response to tissue injury, there was an increase in neutrophils, monocytes, macrophages, as well as an increase in CD19+ CD11b– B lymphocytes. Treatment with pirfenidone had no effect on the number of neutrophils, monocytes, or macrophages, but decreased CD19+CD11b– 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+ lymphocytes through a TIRAP-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.
VersionFinal published version
SponsorsNIH [R01HL107594-06, T32 HL007081]
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