Dudeck, J.* ; Froebel, J.* ; Kotrba, J.* ; Lehmann, C.H.K.* ; Dudziak, D.* ; Speier, S. ; Nedospasov, S.A.* ; Schraven, B.* ; Dudeck, A.*
Engulfment of mast cell secretory granules on skin inflammation boosts dendritic cell migration and priming efficiency.
J. Allergy Clin. Immunol. 143, 1849-1864.e4 (2019)
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 MCderived 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.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Mast Cells ; Dendritic Cells ; Adaptive Immune Response ; T-cell Response ; Skin Inflammation; Tumor-necrosis-factor; T-cells; Neutrophil Recruitment; Cross-presentation; Langerhans Cells; Tnf; Responses; Histamine; Hypertrophy; Modulation
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2019
Prepublished im Jahr
2018
HGF-Berichtsjahr
2018
ISSN (print) / ISBN
0091-6749
e-ISSN
1097-6825
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 143,
Heft: 5,
Seiten: 1849-1864.e4
Artikelnummer: ,
Supplement: ,
Reihe
Verlag
Elsevier
Verlagsort
Amsterdam [u.a.]
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Pancreatic Islet Research (IPI)
POF Topic(s)
90000 - German Center for Diabetes Research
Forschungsfeld(er)
Helmholtz Diabetes Center
PSP-Element(e)
G-502600-005
Förderungen
Copyright
Erfassungsdatum
2018-10-25