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  Upregulation of VCAM-1 in lymphatic collectors supports dendritic cell entry and rapid migration to lymph nodes in inflammation

Arasa, J., Collado-Diaz, V., Kritikos, I., Medina-Sanchez, J. D., Friess, M. C., Sigmund, E. C., et al. (2021). Upregulation of VCAM-1 in lymphatic collectors supports dendritic cell entry and rapid migration to lymph nodes in inflammation. Journal of Experimental Medicine, 218(7): e20201413. doi:10.1084/jem.20201413.

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 Creators:
Arasa, Jorge1, Author
Collado-Diaz, Victor1, Author
Kritikos, Ioannis1, Author
Medina-Sanchez, Jessica Danielly1, Author
Friess, Mona Carina1, Author
Sigmund, Elena Caroline1, Author
Schineis, Philipp1, Author
Hunter, Morgan Campbell1, Author
Tacconi, Carlotta1, Author
Paterson, Neil1, Author
Nagasawa, Takashi1, Author
Kiefer, Friedemann1, Author
Makinen, Taija1, Author
Detmar, Michael1, Author
Moser, Markus2, Author              
Laemmermann, Tim1, Author
Halin, Cornelia1, Author
Affiliations:
1external, ou_persistent22              
2Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              

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Free keywords: ENDOTHELIAL-CELLS; LANGERHANS CELLS; STEADY-STATE; IN-VIVO; SKIN; CAPILLARIES; TRAFFICKING; EXPRESSION; TRANSPORT; DYNAMICSImmunology; Research & Experimental Medicine;
 Abstract: Dendritic cell (DC) migration to draining lymph nodes (dLNs) is a slow process that is believed to begin with DCs approaching and entering into afferent lymphatic capillaries. From capillaries, DCs slowly crawl into lymphatic collectors, where lymph flow induced by collector contraction supports DC detachment and thereafter rapid, passive transport to dLNs. Performing a transcriptomics analysis of dermal endothelial cells, we found that inflammation induces the degradation of the basement membrane (BM) surrounding lymphatic collectors and preferential up-regulation of the DC trafficking molecule VCAM-1 in collectors. In crawl-in experiments performed in ear skin explants, DCs entered collectors in a CCR7- and beta 1 integrin-dependent manner. In vivo, loss of beta 1-integrins in DCs or of VCAM-1 in lymphatic collectors had the greatest impact on DC migration to dLNs at early time points when migration kinetics favor the accumulation of rapidly migrating collector DCs rather than slower capillary DCs. Taken together, our findings identify collector entry as a critical mechanism enabling rapid DC migration to dLNs in inflammation.

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Language(s): eng - English
 Dates: 2021
 Publication Status: Published online
 Pages: 24
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000656304900002
DOI: 10.1084/jem.20201413
 Degree: -

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Title: Journal of Experimental Medicine
Source Genre: Journal
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Publ. Info: Baltimore, Md. : Rockefeller Institute for Medical Research
Pages: - Volume / Issue: 218 (7) Sequence Number: e20201413 Start / End Page: - Identifier: ISSN: 0022-1007
CoNE: https://pure.mpg.de/cone/journals/resource/954925413886