Integrin β1–mediated mast cell immune-surveillance of blood vessel content
Link K, Muhandes L, Polikarpova A, Lämmermann T, Sixt MK, Fässler R, Roers A. Integrin β1–mediated mast cell immune-surveillance of blood vessel content. Journal of Allergy and Clinical Immunology.
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https://doi.org/10.1016/j.jaci.2024.03.022
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Journal Article
| In Press
| English
Scopus indexed
Author
Link, Kristina;
Muhandes, Lina;
Polikarpova, Anastasia;
Lämmermann, Tim;
Sixt, Michael KISTA ;
Fässler, Reinhard;
Roers, Axel
Department
Abstract
Background: IgE-mediated degranulation of mast cells (MCs) provides rapid protection against environmental hazards, including animal venoms. A fraction of tissue-resident MCs intimately associates with blood vessels. These perivascular MCs were reported to extend projections into the vessel lumen and to be the first MCs to acquire intravenously injected IgE, suggesting that IgE loading of MCs depends on their vascular association.
Objective: We sought to elucidate the molecular basis of the MC–blood vessel interaction and to determine its relevance for IgE-mediated immune responses.
Methods: We selectively inactivated the Itgb1 gene, encoding the β1 chain of integrin adhesion molecules (ITGB1), in MCs by conditional gene targeting in mice. We analyzed skin MCs for blood vessel association, surface IgE density, and capability to bind circulating antibody specific for MC surface molecules, as well as in vivo responses to antigen administered via different routes.
Results: Lack of ITGB1 expression severely compromised MC–blood vessel association. ITGB1-deficient MCs showed normal densities of surface IgE but reduced binding of intravenously injected antibodies. While their capacity to degranulate in response to IgE ligation in vivo was unimpaired, anaphylactic responses to antigen circulating in the vasculature were largely abolished.
Conclusions: ITGB1-mediated association of MCs with blood vessels is key for MC immune surveillance of blood vessel content, but is dispensable for slow steady-state loading of endogenous IgE onto tissue-resident MCs.
Publishing Year
Date Published
2024-04-16
Journal Title
Journal of Allergy and Clinical Immunology
Acknowledgement
This work was funded by Deutsche Forschungsgemeinschaft, Germany, grants RO2133/ 9-1 and RO2133/ 9-2 in the setting of FOR2599 and TR156 project C11 (Project-ID 246807620–TRR 156) to A. Roers and Springboard-to-Postdoc grant of the Dresden International Graduate School for Biomedicine and Bioengineering (DIGS-BB), Dresden, Germany, and Fond zur Förderung der Wissenschaftlichen Forschung (FWF), Austria, Hertha Firnberg grant (project number T-1219) to A. Polikarpova.
We thank Dr Michael Gerlach, Core Facility Cellular Imaging, Faculty of Medicine Carl Gustav Carus, TU Dresden, for expert support of in vivo imaging experiments; Grace Wurigamule for help with 2-photon imaging and flow cytometric analysis of mouse skin; and Christina Hiller, Livia Schulze, Madelaine Rickauer, and Christa Haase for providing expert technical assistance.
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Cite this
Link K, Muhandes L, Polikarpova A, et al. Integrin β1–mediated mast cell immune-surveillance of blood vessel content. Journal of Allergy and Clinical Immunology. doi:10.1016/j.jaci.2024.03.022
Link, K., Muhandes, L., Polikarpova, A., Lämmermann, T., Sixt, M. K., Fässler, R., & Roers, A. (n.d.). Integrin β1–mediated mast cell immune-surveillance of blood vessel content. Journal of Allergy and Clinical Immunology. Elsevier. https://doi.org/10.1016/j.jaci.2024.03.022
Link, Kristina, Lina Muhandes, Anastasia Polikarpova, Tim Lämmermann, Michael K Sixt, Reinhard Fässler, and Axel Roers. “Integrin Β1–Mediated Mast Cell Immune-Surveillance of Blood Vessel Content.” Journal of Allergy and Clinical Immunology. Elsevier, n.d. https://doi.org/10.1016/j.jaci.2024.03.022.
K. Link et al., “Integrin β1–mediated mast cell immune-surveillance of blood vessel content,” Journal of Allergy and Clinical Immunology. Elsevier.
Link K, Muhandes L, Polikarpova A, Lämmermann T, Sixt MK, Fässler R, Roers A. Integrin β1–mediated mast cell immune-surveillance of blood vessel content. Journal of Allergy and Clinical Immunology.
Link, Kristina, et al. “Integrin Β1–Mediated Mast Cell Immune-Surveillance of Blood Vessel Content.” Journal of Allergy and Clinical Immunology, Elsevier, doi:10.1016/j.jaci.2024.03.022.
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