Basophils balance healing after myocardial infarction via IL-4/IL-13
Florian Sicklinger, … , David Voehringer, Florian Leuschner
Florian Sicklinger, … , David Voehringer, Florian Leuschner
Published July 1, 2021
Citation Information: J Clin Invest. 2021;131(13):e136778. https://doi.org/10.1172/JCI136778.
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Research Article Cardiology

Basophils balance healing after myocardial infarction via IL-4/IL-13

Abstract

The inflammatory response after myocardial infarction (MI) is a precisely regulated process that greatly affects subsequent remodeling. Here, we show that basophil granulocytes infiltrated infarcted murine hearts, with a peak occurring between days 3 and 7. Antibody-mediated and genetic depletion of basophils deteriorated cardiac function and resulted in enhanced scar thinning after MI. Mechanistically, we found that basophil depletion was associated with a shift from reparative Ly6Clo macrophages toward increased numbers of inflammatory Ly6Chi monocytes in the infarcted myocardium. Restoration of basophils in basophil-deficient mice by adoptive transfer reversed this proinflammatory phenotype. Cellular alterations in the absence of basophils were accompanied by lower cardiac levels of IL-4 and IL-13, two major cytokines secreted by basophils. Mice with basophil-specific IL-4/IL-13 deficiency exhibited a similarly altered myeloid response with an increased fraction of Ly6Chi monocytes and aggravated cardiac function after MI. In contrast, IL-4 induction in basophils via administration of the glycoprotein IPSE/α-1 led to improved post-MI healing. These results in mice were corroborated by the finding that initially low counts of blood basophils in patients with acute MI were associated with a worse cardiac outcome after 1 year, characterized by a larger scar size. In conclusion, we show that basophils promoted tissue repair after MI by increasing cardiac IL-4 and IL-13 levels.

Authors

Florian Sicklinger, Ingmar Sören Meyer, Xue Li, Daniel Radtke, Severin Dicks, Moritz P. Kornadt, Christina Mertens, Julia K. Meier, Kory J. Lavine, Yunhang Zhang, Tim Christian Kuhn, Tobias Terzer, Jyoti Patel, Melanie Boerries, Gabriele Schramm, Norbert Frey, Hugo A. Katus, David Voehringer, Florian Leuschner

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Figure 3

Baso-KO mice show deteriorated healing after MI.

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Baso-KO mice show deteriorated healing after MI. (A) Echocardiographic e...
(A) Echocardiographic evaluation of baseline EF in WT and Baso-KO mice. (B) Plasma cTnT values in WT and Baso-KO mice measured 24 hours after LAD ligation. (C–F) Echocardiographic results for Baso-KO and WT mice 4 weeks after MI. P values were determined by 2-tailed Student’s t test. (G) Quantification of heart weight to body weight ratio 4 weeks after MI. P value was determined by 2-tailed Student’s t test. (H and I) Scar thickness and LV lumen area were quantified by histological evaluation 4 weeks after MI (n = 6–8). Data show the mean ± SD. P values were determined by 2-tailed Student’s t test. (J and K) Representative echocardiographic and histological images of WT and Baso-KO mice 4 weeks after MI. 3D plots show radial displacement over 3 cardiac cycles. Histological sections were stained with Masson’s trichrome to detect fibrosis. Scale bars: 500 μm. Ant. sept., anterior septal; Post., posterior.