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 firstname.lastname@example.org.
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]
- Pirfenidone mitigates left ventricular fibrosis and dysfunction after myocardial infarction and reduces arrhythmias.
- Authors: Nguyen DT, Ding C, Wilson E, Marcus GM, Olgin JE
- Issue date: 2010 Oct
- Topiramate modulates post-infarction inflammation primarily by targeting monocytes or macrophages.
- Authors: Wang Z, Huang S, Sheng Y, Peng X, Liu H, Jin N, Cai J, Shu Y, Li T, Li P, Fan C, Hu X, Zhang W, Long R, You Y, Huang C, Song Y, Xiang C, Wang J, Yang Y, Liu K
- Issue date: 2017 Apr 1
- Interleukin-37 and Dendritic Cells Treated With Interleukin-37 Plus Troponin I Ameliorate Cardiac Remodeling After Myocardial Infarction.
- Authors: Zhu R, Sun H, Yu K, Zhong Y, Shi H, Wei Y, Su X, Xu W, Luo Q, Zhang F, Zhu Z, Meng K, Zhao X, Liu Y, Mao Y, Cheng P, Mao X, Zeng Q
- Issue date: 2016 Dec 5
- Inhibition of RIP1-dependent necrosis prevents adverse cardiac remodeling after myocardial ischemia-reperfusion in vivo.
- Authors: Oerlemans MI, Liu J, Arslan F, den Ouden K, van Middelaar BJ, Doevendans PA, Sluijter JP
- Issue date: 2012 Jul
- Differential contribution of monocytes to heart macrophages in steady-state and after myocardial infarction.
- Authors: Heidt T, Courties G, Dutta P, Sager HB, Sebas M, Iwamoto Y, Sun Y, Da Silva N, Panizzi P, van der Laan AM, Swirski FK, Weissleder R, Nahrendorf M
- Issue date: 2014 Jul 7