title: Intralymphatic CCL21 Promotes Tissue Egress of Dendritic Cells through Afferent Lymphatic Vessels.
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.
authors.affiliation: Institute of Pharmaceutical Sciences, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Erica
authors.initials: E
authors.lastname: Russo
authors.affiliation: Institute of Pharmaceutical Sciences, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Teijeira
authors.affiliation: IST Austria, Institute of Science and Technology Austria, 3400 Klosterneuburg, Austria.
authors.forename: Kari
authors.initials: K
authors.lastname: Vaahtomeri
authors.affiliation: Institute of Pharmaceutical Sciences, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Ann-Helen
authors.initials: AH
authors.lastname: Willrodt
authors.affiliation: Institute of Pharmaceutical Sciences, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Joël S
authors.initials: JS
authors.lastname: Bloch
authors.affiliation: Institute of Pharmaceutical Sciences, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Nitschké
authors.affiliation: Albert Einstein College of Medicine, New York, NY 10461, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Santambrogio
authors.affiliation: Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Dontscho
authors.initials: D
authors.lastname: Kerjaschki
authors.affiliation: IST Austria, Institute of Science and Technology Austria, 3400 Klosterneuburg, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Sixt
authors.affiliation: Institute of Pharmaceutical Sciences, ETH Zurich, 8093 Zurich, Switzerland. Electronic address: cornelia.halin@pharma.ethz.ch.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Halin
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology; D002465:Cell Movement; D054421:Chemokine CCL21 / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D004423:Ear; D004729:Endothelium, Lymphatic / Q000276:immunology* / Q000648:ultrastructure; D015870:Gene Expression; D008198:Lymph Nodes / Q000276:immunology* / Q000648:ultrastructure; D042601:Lymphatic Vessels / Q000276:immunology* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012212:Rheology; D012867:Skin / Q000166:cytology / Q000276:immunology; D059008:Time-Lapse Imaging
chemical_list: D054421:Chemokine CCL21