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- Title
Basophils balance healing after myocardial infarction via IL-4/IL-13.
- Authors
Sicklinger, Florian; Sören Meyer, Ingmar; Xue Li; Radtke, Daniel; Dicks, Severin; Kornadt, Moritz P.; Mertens, Christina; Meier, Julia K.; Lavine, Kory J.; Yunhang Zhang; Kuhn, Tim Christian; Terzer, Tobias; Patel, Jyoti; Boerries, Melanie; Schramm, Gabriele; Frey, Norbert; Katus, Hugo A.; Voehringer, David; Leuschner, Florian; Meyer, Ingmar Sören
- 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.
- Subjects
BASOPHILS; MYOCARDIAL infarction; HEALING; PHENOTYPES; GRANULOCYTES; BASOPHIL physiology; INTERLEUKINS; BIOLOGICAL models; RESEARCH; ANIMAL experimentation; RESEARCH methodology; MEDICAL cooperation; EVALUATION research; COMPARATIVE studies; MICE
- Publication
Journal of Clinical Investigation, 2021, Vol 131, Issue 13, p1
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI136778