Journal Article

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

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

2021

Overview

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.

• Publisher: American Society for Clinical Investigation
• Subject: Ablation / Adoptive transfer / Animals / Antibodies / Basophils / Basophils - immunology / Basophils - pathology / Basophils - physiology / Biomedical research / Cardiac function / Cytokines / Development and progression / Disease Models, Animal / Flow cytometry / Gene expression / Granulocytes / Health aspects / Heart / Heart attack / Heart attacks / Humans / Inflammation / Interleukin 13 / Interleukin 4 / Interleukin-13 - deficiency / Interleukin-13 - genetics / Interleukin-13 - immunology / Interleukin-4 - deficiency / Interleukin-4 - genetics / Interleukin-4 - immunology / Leukocytes (basophilic) / Leukocytes (granulocytic) / Macrophages / Mice / Mice, Inbred C57BL / Mice, Knockout / Monocytes / Myocardial infarction / Myocardial Infarction - immunology / Myocardial Infarction - pathology / Myocardial Infarction - physiopathology / Myocardium / Phenotypes / Physiological aspects / Regeneration (Biology) / Rodents / ST Elevation Myocardial Infarction - immunology / ST Elevation Myocardial Infarction - pathology / ST Elevation Myocardial Infarction - physiopathology