Edited by Ajay Chawla, University of California, San Francisco, CA, and accepted by Editorial Board Member Philippa Marrack September 13, 2019 (received for review July 9, 2019)
Myocardial infarction (MI) remains a leading cause of mortality and morbidity worldwide. Although it is recognized that a balanced and timely terminated proinflammatory response following acute MI is essential in promoting tissue repair/regeneration, the underlying regulatory mechanisms are poorly defined. In this report, we show that IL-10–producing B cells in mice: 1) Are enriched in pericardial adipose tissues (PATs) and influenced by cytokines preferentially expressed in these tissues; 2) expand in PATs following MI and accumulate in the infarcted heart during the resolution of MI-induced inflammation; and 3) facilitate resolution of inflammation and reduce myocardial injury to preserve cardiac function after MI. These findings identify IL-10–producing B cells, in particular those in PATs, as therapeutic targets for MI.
Acute myocardial infarction (MI) provokes an inflammatory response in the heart that removes damaged tissues to facilitate tissue repair/regeneration. However, overactive and prolonged inflammation compromises healing, which may be counteracted by antiinflammatory mechanisms. A key regulatory factor in an inflammatory response is the antiinflammatory cytokine IL-10, which can be produced by a number of immune cells, including subsets of B lymphocytes. Here, we investigated IL-10–producing B cells in pericardial adipose tissues (PATs) and their role in the healing process following acute MI in mice. We found that IL-10–producing B cells were enriched in PATs compared to other adipose depots throughout the body, with the majority of them bearing a surface phenotype consistent with CD5+ B-1a cells (CD5+ B cells). These cells were detected early in life, maintained a steady presence during adulthood, and resided in fat-associated lymphoid clusters. The cytokine IL-33 and the chemokine CXCL13 were preferentially expressed in PATs and contributed to the enrichment of IL-10–producing CD5+ B cells. Following acute MI, the pool of CD5+ B cells was expanded in PATs. These cells accumulated in the infarcted heart during the resolution of MI-induced inflammation. B cell-specific deletion of IL-10 worsened cardiac function, exacerbated myocardial injury, and delayed resolution of inflammation following acute MI. These results revealed enrichment of IL-10–producing B cells in PATs and a significant contribution of these cells to the antiinflammatory processes that terminate MI-induced inflammation. Together, these findings have identified IL-10–producing B cells as therapeutic targets to improve the outcome of MI.
Author contributions: L.W. and L.V.K. designed research; L.W., R.D., C.D.C., J.L.P., G.Y., Q.Z., and Z.W. performed research; L.W. and H.L. analyzed data; and L.W. and L.V.K. wrote the paper.
The authors declare no competing interest.
This article is a PNAS Direct Submission. A.C. is a guest editor invited by the Editorial Board.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1911464116/-/DCSupplemental.
Published under the PNAS license.
