Healing and repair after myocardial infarction: the forgotten but resurgent basophil
Sumanth D. Prabhu
Sumanth D. Prabhu
Published July 1, 2021
Citation Information: J Clin Invest. 2021;131(13):e150555. https://doi.org/10.1172/JCI150555.
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Commentary

Healing and repair after myocardial infarction: the forgotten but resurgent basophil

Abstract

The biphasic wound-healing response in the heart after myocardial infarction involves an initial inflammatory phase followed by a more prolonged period of inflammation resolution, tissue repair, and scar formation. Infiltrating proinflammatory Ly6Chi monocytes and monocyte-derived macrophages are key drivers of the inflammatory phase and are also the source of the locally generated reparative macrophages that promote inflammation resolution. In this issue of the JCI, Sicklinger et al. from the Leuschner laboratory uncover a salutary role for cardiac basophils in this process. The authors demonstrated that basophils promote healing and proper scar formation and also limit late cardiac remodeling by augmenting reparative macrophages in the infarcted heart, in part via basophil-derived enhancement of cardiac IL-4 and IL-13 levels. These findings underscore the potentially disproportionate (relative to cell numbers) yet essential biological effects of immune cells of low abundance on cardiac repair and remodeling, related in part to amplification of downstream macrophage responses via secreted cytokines.

Authors

Sumanth D. Prabhu

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Figure 1

Schematic of the inflammatory and healing response after MI.

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Schematic of the inflammatory and healing response after MI. In mice, th...
In mice, the wound repair process after MI involves an early inflammatory phase and an inflammation resolution phase. The inflammatory phase is primarily dominated by infiltrating proinflammatory Ly6Chi monocytes and macrophages. The more prolonged healing phase leads to scar formation and is characterized by reparative Ly6Clo macrophages generated locally in the heart. Reparative macrophage differentiation is facilitated by efferocytosis and requires the nuclear hormone receptor Nr4a1. In this issue of the JCI, Sicklinger et al. (15) report a central role for basophils in the healing process, in large part related to their secretion of IL-4 and IL-13, which in turn promotes reparative macrophage differentiation and inflammation resolution. Hence, basophils play an essential role in the fidelity of post-MI cardiac repair and the subsequent limitation of long-term adverse cardiac remodeling. CCR2, C-C motif chemokine receptor 2; IL-4R, IL-4 receptor.