%0 Journal Article
%T CCR3-dependent eosinophil recruitment is regulated by sialyltransferase ST3Gal-IV.
%A Immler R
%A Nussbaumer K
%A Doerner A
%A El Bounkari O
%A Huber S
%A Abisch J
%A Napoli M
%A Schmidt S
%A Margraf A
%A Pruenster M
%A Rohwedder I
%A Lange-Sperandio B
%A Mall MA
%A de Jong R
%A Ohnmacht C
%A Bernhagen J
%A Voehringer D
%A Marth JD
%A Frommhold D
%A Sperandio M
%J Proc Natl Acad Sci U S A
%V 121
%N 19
%D 2024 May 7
%M 38687790
%F 12.779
%R 10.1073/pnas.2319057121
%X 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.