IL-10-producing B cells are enriched in murine pericardial adipose tissues and ameliorate the outcome of acute myocardial infarction.

Wu L, Dalal R, Cao CD, Postoak JL, Yang G, Zhang Q, Wang Z, Lal H, Van Kaer L
Proc Natl Acad Sci U S A. 2019 116 (43): 21673-21684

PMID: 31591231 · PMCID: PMC6815157 · DOI:10.1073/pnas.1911464116

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.

MeSH Terms (16)

Adipose Tissue Animals B-Lymphocytes Chemokine CXCL13 Female Inflammation Interleukin-10 Interleukin-33 Lymphocyte Count Male Mice Mice, Inbred C57BL Mice, Knockout Myocardial Infarction Pericardium Regeneration

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