Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Physician-Scientist Development
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • In-Press Preview
    • Resource and Technical Advances
    • Clinical Research and Public Health
    • Research Letters
    • Editorials
    • Perspectives
    • Physician-Scientist Development
    • Reviews
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Resource and Technical Advances
  • Clinical Research and Public Health
  • Research Letters
  • Editorials
  • Perspectives
  • Physician-Scientist Development
  • Reviews
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Transfers
  • Advertising
  • Job board
  • Contact
Csk-mediated Src family kinase regulation dampens neutrophil infiltration during pulmonary infection
Wida Amini, … , Anika Cappenberg, Alexander Zarbock
Wida Amini, … , Anika Cappenberg, Alexander Zarbock
Published June 10, 2025
Citation Information: JCI Insight. 2025;10(14):e188323. https://doi.org/10.1172/jci.insight.188323.
View: Text | PDF
Research Article Immunology Inflammation Article has an altmetric score of 7

Csk-mediated Src family kinase regulation dampens neutrophil infiltration during pulmonary infection

  • Text
  • PDF
Abstract

Neutrophil recruitment is crucial for pathogen elimination. However, precise control of the inflammatory response prevents overshooting reactions. Neutrophil activation initiates signaling, resulting in integrin β2 (Itgb2) activation and neutrophil arrest. Src family kinases are involved in multiple cellular processes and are negatively regulated by the C-terminal Src kinase (Csk). During this study, we investigated the mechanism by which Csk regulates integrin activation and neutrophil recruitment. Here, we demonstrated that Csk deficiency in murine neutrophils resulted in increased neutrophil adhesion to the endothelium along with decreased neutrophil transmigration into inflamed tissues compared with their littermate controls. In bacterial pneumonia, infected Csk-deficient mice showed higher bacterial burdens and decreased neutrophil recruitment, while other immune cell counts and cytokine levels were not significantly different compared to control. Analyses of Csk-deficient neutrophils revealed an increased Itgb2 affinity, leading to reduced migration and intravascular crawling. Mechanistically, elevated cAMP levels increased protein kinase A activity, which subsequently enhanced Csk activation. Csk, in turn, suppressed Src family kinase activation through phosphorylation (Y529). Hence, Csk-mediated regulation of neutrophil infiltration contributes to maintain a balanced immune response during bacterial pneumonia.

Authors

Wida Amini, Lena Schemmelmann, Jan-Niklas Heming, Marina Oguama, Katharina Thomas, Helena Block, Pia Lindental, Bernadette Bardel, Andreas Margraf, Oliver Soehnlein, Anika Cappenberg, Alexander Zarbock

×

Full Text PDF

Download PDF (1.33 MB) | Download high-resolution PDF (6.52 MB)

Copyright © 2025 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts

Posted by 16 X users
Referenced by 3 Bluesky users
4 readers on Mendeley
See more details