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Immler, Roland; Nussbaumer, Katrin; Doerner, Axel; El Bounkari, Omar; Huber, Silke; Abisch, Janine; Napoli, Matteo; Schmidt, Sarah; Margraf, Andreas; Pruenster, Monika; Rohwedder, Ina; Lange-Sperandio, Baerbel; Mall, Marcus A.; de Jong, Renske; Ohnmacht, Caspar; Bernhagen, Juergen; Voehringer, David; Marth, Jamey D.; Frommhold, David; Sperandio, Markus

CCR3-dependent eosinophil recruitment is regulated by sialyltransferase ST3Gal-IV

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  • Medientyp: E-Artikel
  • Titel: CCR3-dependent eosinophil recruitment is regulated by sialyltransferase ST3Gal-IV
  • Beteiligte: Immler, Roland; Nussbaumer, Katrin; Doerner, Axel; El Bounkari, Omar; Huber, Silke; Abisch, Janine; Napoli, Matteo; Schmidt, Sarah; Margraf, Andreas; Pruenster, Monika; Rohwedder, Ina; Lange-Sperandio, Baerbel; Mall, Marcus A.; de Jong, Renske; Ohnmacht, Caspar; Bernhagen, Juergen; Voehringer, David; Marth, Jamey D.; Frommhold, David; Sperandio, Markus
  • Erschienen: Proceedings of the National Academy of Sciences, 2024
  • Erschienen in: Proceedings of the National Academy of Sciences, 121 (2024) 19
  • Sprache: Englisch
  • DOI: 10.1073/pnas.2319057121
  • ISSN: 0027-8424; 1091-6490
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: Eosinophil recruitment is a pathological hallmark of many allergic and helminthic diseases. Here, we investigated chemokine receptor CCR3-induced eosinophil recruitment in sialyltransferase St3gal4 −/− mice. We found a marked decrease in eosinophil extravasation into CCL11-stimulated cremaster muscles and into the inflamed peritoneal cavity of St3gal4 −/− mice. Ex vivo flow chamber assays uncovered reduced adhesion of St3gal4 −/− compared to wild type eosinophils. Using flow cytometry, we show reduced binding of CCL11 to St3gal4 −/− eosinophils. Further, we noted reduced binding of CCL11 to its chemokine receptor CCR3 isolated from St3gal4 −/− eosinophils. This was accompanied by almost absent CCR3 internalization of CCL11-stimulated St3gal4 −/− eosinophils. Applying an ovalbumin-induced allergic airway disease model, we found a dramatic reduction in eosinophil numbers in bronchoalveolar lavage fluid following intratracheal challenge with ovalbumin in St3gal4 -deficient mice. Finally, we also investigated tissue-resident eosinophils under homeostatic conditions and found reduced resident eosinophil numbers in the thymus and adipose tissue in the absence of ST3Gal-IV. Taken together, our results demonstrate an important role of ST3Gal-IV in CCR3-induced eosinophil recruitment in vivo rendering this enzyme an attractive target in reducing unwanted eosinophil infiltration in various disorders including allergic diseases.