Engulfment of mast cell secretory granules on skin inflammation boosts dendritic cell migration and priming efficiency

Journal article


Publication Details

Author(s): Dudeck J, Froebel J, Kotrba J, Lehmann C, Dudziak D, Speier S, Nedospasov SA, Schraven B, Dudeck A
Journal: Journal of Allergy and Clinical Immunology
Publication year: 2019
Volume: 143
Journal issue: 5
Pages range: 1849-1864.e4
ISSN: 0091-6749


Abstract

Background: Mast cells (MCs)are best known as key effector cells of allergic reactions, but they also play an important role in host defense against pathogens. Despite increasing evidence for a critical effect of MCs on adaptive immunity, the underlying mechanisms are poorly understood. Objective: Here we monitored MC intercellular communication with dendritic cells (DCs), MC activation, and degranulation and tracked the fate of exocytosed mast cell granules (MCGs)during skin inflammation. Methods: Using a strategy to stain intracellular MCGs in vivo, we tracked the MCG fate after skin inflammation–induced MC degranulation. Furthermore, exogenous MCGs were applied to MC-deficient mice by means of intradermal injection. MCG effects on DC functionality and adaptive immune responses in vivo were assessed by combining intravital multiphoton microscopy with flow cytometry and functional assays. Results: We demonstrate that dermal DCs engulf the intact granules exocytosed by MCs on skin inflammation. Subsequently, the engulfed MCGs are actively shuttled to skin-draining lymph nodes and finally degraded inside DCs within the lymphoid tissue. Most importantly, MCG uptake promotes DC maturation and migration to skin-draining lymph nodes, partially through MC-derived TNF, and boosts their T-cell priming efficiency. Surprisingly, exogenous MCGs alone are sufficient to induce a prominent DC activation and T-cell response. Conclusion: Our study highlights a unique feature of peripheral MCs to affect lymphoid tissue–borne adaptive immunity over distance by modifying DC functionality through delivery of granule-stored mediators.


FAU Authors / FAU Editors

Dudziak, Diana Prof. Dr.
Professur für die Biologie Dendritischer Zellen
Lehmann, Christian Dr. rer. nat.
Hautklinik


External institutions
Engelhardt Institute of Molecular Biology (EIMB)
Otto-von-Guericke-Universität Magdeburg
Technische Universität Dresden


How to cite

APA:
Dudeck, J., Froebel, J., Kotrba, J., Lehmann, C., Dudziak, D., Speier, S.,... Dudeck, A. (2019). Engulfment of mast cell secretory granules on skin inflammation boosts dendritic cell migration and priming efficiency. Journal of Allergy and Clinical Immunology, 143(5), 1849-1864.e4. https://dx.doi.org/10.1016/j.jaci.2018.08.052

MLA:
Dudeck, Jan, et al. "Engulfment of mast cell secretory granules on skin inflammation boosts dendritic cell migration and priming efficiency." Journal of Allergy and Clinical Immunology 143.5 (2019): 1849-1864.e4.

BibTeX: 

Last updated on 2019-15-05 at 00:08