@article{10.1172/JCI136778, author = {Florian Sicklinger AND Ingmar Sören Meyer AND Xue Li AND Daniel Radtke AND Severin Dicks AND Moritz P. Kornadt AND Christina Mertens AND Julia K. Meier AND Kory J. Lavine AND Yunhang Zhang AND Tim Christian Kuhn AND Tobias Terzer AND Jyoti Patel AND Melanie Boerries AND Gabriele Schramm AND Norbert Frey AND Hugo A. Katus AND David Voehringer AND Florian Leuschner}, journal = {The Journal of Clinical Investigation}, publisher = {The American Society for Clinical Investigation}, title = {Basophils balance healing after myocardial infarction via IL-4/IL-13}, year = {2021}, month = {7}, volume = {131}, url = {https://www.jci.org/articles/view/136778}, 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.}, number = {13}, doi = {10.1172/JCI136778}, url = {https://doi.org/10.1172/JCI136778}, }