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000169666 1001_ $$aSicklinger, Florian$$b0
000169666 245__ $$aBasophils balance healing after myocardial infarction via IL-4/IL-13.
000169666 260__ $$aAnn Arbor, Mich.$$bASCJ$$c2021
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000169666 520__ $$aThe inflammatory response after myocardial infarction (MI) is a precisely regulated process that greatly affects subsequent remodeling. Here, we show that basophil granulocytes infiltrated infarcted murine hearts, with a peak occurring between days 3 and 7. Antibody-mediated and genetic depletion of basophils deteriorated cardiac function and resulted in enhanced scar thinning after MI. Mechanistically, we found that basophil depletion was associated with a shift from reparative Ly6Clo macrophages toward increased numbers of inflammatory Ly6Chi monocytes in the infarcted myocardium. Restoration of basophils in basophil-deficient mice by adoptive transfer reversed this proinflammatory phenotype. Cellular alterations in the absence of basophils were accompanied by lower cardiac levels of IL-4 and IL-13, two major cytokines secreted by basophils. Mice with basophil-specific IL-4/IL-13 deficiency exhibited a similarly altered myeloid response with an increased fraction of Ly6Chi monocytes and aggravated cardiac function after MI. In contrast, IL-4 induction in basophils via administration of the glycoprotein IPSE/α-1 led to improved post-MI healing. These results in mice were corroborated by the finding that initially low counts of blood basophils in patients with acute MI were associated with a worse cardiac outcome after 1 year, characterized by a larger scar size. In conclusion, we show that basophils promoted tissue repair after MI by increasing cardiac IL-4 and IL-13 levels.
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000169666 650_7 $$2Other$$aCardiology
000169666 650_7 $$2Other$$aCardiovascular disease
000169666 650_7 $$2Other$$aHeart failure
000169666 650_7 $$2Other$$aInnate immunity
000169666 7001_ $$aMeyer, Ingmar Sören$$b1
000169666 7001_ $$aLi, Xue$$b2
000169666 7001_ $$aRadtke, Daniel$$b3
000169666 7001_ $$aDicks, Severin$$b4
000169666 7001_ $$aKornadt, Moritz P$$b5
000169666 7001_ $$aMertens, Christina$$b6
000169666 7001_ $$aMeier, Julia K$$b7
000169666 7001_ $$aLavine, Kory J$$b8
000169666 7001_ $$aZhang, Yunhang$$b9
000169666 7001_ $$aKuhn, Tim Christian$$b10
000169666 7001_ $$0P:(DE-He78)9c4af0f5ceb3a2072b3736274eadf20e$$aTerzer, Tobias$$b11
000169666 7001_ $$aPatel, Jyoti$$b12
000169666 7001_ $$0P:(DE-He78)49bdb7cb4094fbf35c269ffa3e93ebc6$$aBörries, Melanie$$b13$$udkfz
000169666 7001_ $$aSchramm, Gabriele$$b14
000169666 7001_ $$aFrey, Norbert$$b15
000169666 7001_ $$aKatus, Hugo A$$b16
000169666 7001_ $$aVoehringer, David$$b17
000169666 7001_ $$aLeuschner, Florian$$b18
000169666 773__ $$0PERI:(DE-600)2018375-6$$a10.1172/JCI136778$$gVol. 131, no. 13, p. e136778$$n13$$pe136778$$tThe journal of clinical investigation$$v131$$x1558-8238$$y2021
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