Journal Article

DKFZ-2021-01488

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Basophils balance healing after myocardial infarction via IL-4/IL-13.

Sicklinger, F. ; Meyer, I. S. ; Li, X. ; Radtke, D. ; Dicks, S. ; Kornadt, M. P. ; Mertens, C. ; Meier, J. K. ; Lavine, K. J. ; Zhang, Y. ; Kuhn, T. C. ; Terzer, T.DKFZ* ; Patel, J. ; Börries, M.DKFZ* ; Schramm, G. ; Frey, N. ; Katus, H. A. ; Voehringer, D. ; Leuschner, F.

2021
ASCJ Ann Arbor, Mich.

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Please use a persistent id in citations: doi:10.1172/JCI136778

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.

Keyword(s): Cardiology ; Cardiovascular disease ; Heart failure ; Innate immunity

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Contributing Institute(s):

1. C060 Biostatistik (C060)
2. DKTK Koordinierungsstelle Freiburg (FR01)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2021

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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