Intralymphatic CCL21 Promotes Tissue Egress of Dendritic Cells through Afferent Lymphatic Vessels

Erica Russo, Alvaro Teijeira, Kari Vaahtomeri, Ann Helen Willrodt, Joël S. Bloch, Maximilian Nitschké, Laura Santambrogio, Dontscho Kerjaschki, Michael Sixt, Cornelia Halin

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

To induce adaptive immunity, dendritic cells (DCs) migrate through afferent lymphatic vessels (LVs) to draining lymph nodes (dLNs). This process occurs in several consecutive steps. Upon entry into lymphatic capillaries, DCs first actively crawl into downstream collecting vessels. From there, they are next passively and rapidly transported to the dLN by lymph flow. Here, we describe a role for the chemokine CCL21 in intralymphatic DC crawling. Performing time-lapse imaging in murine skin, we found that blockade of CCL21-but not the absence of lymph flow-completely abolished DC migration from capillaries toward collecting vessels and reduced the ability of intralymphatic DCs to emigrate from skin. Moreover, we found that in vitro low laminar flow established a CCL21 gradient along lymphatic endothelial monolayers, thereby inducing downstream-directed DC migration. These findings reveal a role for intralymphatic CCL21 in promoting DC trafficking to dLNs, through the formation of a flow-induced gradient.

Original languageEnglish (US)
Pages (from-to)1723-1734
Number of pages12
JournalCell Reports
Volume14
Issue number7
DOIs
StatePublished - Feb 23 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Russo, E., Teijeira, A., Vaahtomeri, K., Willrodt, A. H., Bloch, J. S., Nitschké, M., Santambrogio, L., Kerjaschki, D., Sixt, M., & Halin, C. (2016). Intralymphatic CCL21 Promotes Tissue Egress of Dendritic Cells through Afferent Lymphatic Vessels. Cell Reports, 14(7), 1723-1734. https://doi.org/10.1016/j.celrep.2016.01.048