TY  - JOUR
AU  - Sicklinger, Florian
AU  - Meyer, Ingmar Sören
AU  - Li, Xue
AU  - Radtke, Daniel
AU  - Dicks, Severin
AU  - Kornadt, Moritz P
AU  - Mertens, Christina
AU  - Meier, Julia K
AU  - Lavine, Kory J
AU  - Zhang, Yunhang
AU  - Kuhn, Tim Christian
AU  - Terzer, Tobias
AU  - Patel, Jyoti
AU  - Börries, Melanie
AU  - Schramm, Gabriele
AU  - Frey, Norbert
AU  - Katus, Hugo A
AU  - Voehringer, David
AU  - Leuschner, Florian
TI  - Basophils balance healing after myocardial infarction via IL-4/IL-13.
JO  - The journal of clinical investigation
VL  - 131
IS  - 13
SN  - 1558-8238
CY  - Ann Arbor, Mich.
PB  - ASCJ
M1  - DKFZ-2021-01488
SP  - e136778
PY  - 2021
AB  - 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.
KW  - Cardiology (Other)
KW  - Cardiovascular disease (Other)
KW  - Heart failure (Other)
KW  - Innate immunity (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:34196299
DO  - DOI:10.1172/JCI136778
UR  - https://inrepo02.dkfz.de/record/169666
ER  -