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

Immler R, Nussbaumer K, Doerner A, El Bounkari O, Huber S, Abisch J, Napoli M, Schmidt S, Margraf A, Pruenster M, Rohwedder I, Lange-Sperandio B, Mall MA, de Jong R, Ohnmacht C, Bernhagen J, Voehringer D, Marth JD, Frommhold D, Sperandio M (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Proceedings of the National Academy of Sciences of the United States of America National Academy of Sciences

Book Volume: 121

Pages Range: e2319057121

Journal Issue: 19

DOI: 10.1073/pnas.2319057121

Abstract

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.

Involved external institutions

Klinikum der Universität München DE Germany (DE) Ruprecht-Karls-Universität Heidelberg DE Germany (DE) Freie Universität Berlin DE Germany (DE) Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE) Ludwig-Maximilians-Universität (LMU) DE Germany (DE) Sanford Burnham Prebys Medical Discovery Institute US United States (USA) (US)

How to cite

APA:

Immler, R., Nussbaumer, K., Doerner, A., El Bounkari, O., Huber, S., Abisch, J.,... Sperandio, M. (2024). CCR3-dependent eosinophil recruitment is regulated by sialyltransferase ST3Gal-IV. Proceedings of the National Academy of Sciences of the United States of America, 121(19), e2319057121. https://doi.org/10.1073/pnas.2319057121

MLA:

Immler, Roland, et al. "CCR3-dependent eosinophil recruitment is regulated by sialyltransferase ST3Gal-IV." Proceedings of the National Academy of Sciences of the United States of America 121.19 (2024): e2319057121.

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