Engulfment of mast cell secretory granules on skin inflammation boosts dendritic cell migration and priming efficiency - 04/05/19
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.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Mast cells, dendritic cells, adaptive immune response, T-cell response, skin inflammation
Abbreviations used : AF, BP, CFSE, CHS, DC, DNFB, eGFP, FITC, GFP, LN, MC, MCG, MFI, OVA, PMC, TR, WT
Plan
Supported by grants from the German Research Foundation (DFG; grants DU1172/2 [Priority Program 1468], DU1172/3 [Priority Program 1394], and CRC854 project A28N; to A.D.). D.D. was funded by the DFG (CRC1181-TPA7) and the EFI-Initiative BIG-Thera. D.D. and C.H.K.L. were funded by the Interdisciplinary Center for Clinical Research (IZKF-A65 and IZKF-J54). S.A.N. was supported by grant 14-50-00060 from the Russian Science Foundation. |
|
Disclosure of potential conflict of interest: These authors declare that they have no relevant conflicts of interest. |
Vol 143 - N° 5
P. 1849 - mai 2019 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?