Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Immune Environment in Glioblastoma (Upcoming)
    • Korsmeyer Award 25th Anniversary Collection (Jan 2023)
    • Aging (Jul 2022)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • Circadian Rhythm (Oct 2021)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Research letters
    • Letters to the editor
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Research letters
  • Letters to the editor
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Basophils balance healing after myocardial infarction via IL-4/IL-13
Florian Sicklinger, … , David Voehringer, Florian Leuschner
Florian Sicklinger, … , David Voehringer, Florian Leuschner
Published July 1, 2021
Citation Information: J Clin Invest. 2021;131(13):e136778. https://doi.org/10.1172/JCI136778.
View: Text | PDF
Research Article Cardiology

Basophils balance healing after myocardial infarction via IL-4/IL-13

  • Text
  • PDF
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.

Authors

Florian Sicklinger, Ingmar Sören Meyer, Xue Li, Daniel Radtke, Severin Dicks, Moritz P. Kornadt, Christina Mertens, Julia K. Meier, Kory J. Lavine, Yunhang Zhang, Tim Christian Kuhn, Tobias Terzer, Jyoti Patel, Melanie Boerries, Gabriele Schramm, Norbert Frey, Hugo A. Katus, David Voehringer, Florian Leuschner

×

Figure 3

Baso-KO mice show deteriorated healing after MI.

Options: View larger image (or click on image) Download as PowerPoint
Baso-KO mice show deteriorated healing after MI.
(A) Echocardiographic e...
(A) Echocardiographic evaluation of baseline EF in WT and Baso-KO mice. (B) Plasma cTnT values in WT and Baso-KO mice measured 24 hours after LAD ligation. (C–F) Echocardiographic results for Baso-KO and WT mice 4 weeks after MI. P values were determined by 2-tailed Student’s t test. (G) Quantification of heart weight to body weight ratio 4 weeks after MI. P value was determined by 2-tailed Student’s t test. (H and I) Scar thickness and LV lumen area were quantified by histological evaluation 4 weeks after MI (n = 6–8). Data show the mean ± SD. P values were determined by 2-tailed Student’s t test. (J and K) Representative echocardiographic and histological images of WT and Baso-KO mice 4 weeks after MI. 3D plots show radial displacement over 3 cardiac cycles. Histological sections were stained with Masson’s trichrome to detect fibrosis. Scale bars: 500 μm. Ant. sept., anterior septal; Post., posterior.

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts