%0 Journal Article
%A Sicklinger, Florian
%A Meyer, Ingmar Sören
%A Li, Xue
%A Radtke, Daniel
%A Dicks, Severin
%A Kornadt, Moritz P
%A Mertens, Christina
%A Meier, Julia K
%A Lavine, Kory J
%A Zhang, Yunhang
%A Kuhn, Tim Christian
%A Terzer, Tobias
%A Patel, Jyoti
%A Börries, Melanie
%A Schramm, Gabriele
%A Frey, Norbert
%A Katus, Hugo A
%A Voehringer, David
%A Leuschner, Florian
%T Basophils balance healing after myocardial infarction via IL-4/IL-13.
%J The journal of clinical investigation
%V 131
%N 13
%@ 1558-8238
%C Ann Arbor, Mich.
%I ASCJ
%M DKFZ-2021-01488
%P e136778
%D 2021
%X 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.
%K Cardiology (Other)
%K Cardiovascular disease (Other)
%K Heart failure (Other)
%K Innate immunity (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:34196299
%R 10.1172/JCI136778
%U https://inrepo02.dkfz.de/record/169666