TY - JOUR
T1 - Intralymphatic CCL21 Promotes Tissue Egress of Dendritic Cells through Afferent Lymphatic Vessels
AU - Russo, Erica
AU - Teijeira, Alvaro
AU - Vaahtomeri, Kari
AU - Willrodt, Ann Helen
AU - Bloch, Joël S.
AU - Nitschké, Maximilian
AU - Santambrogio, Laura
AU - Kerjaschki, Dontscho
AU - Sixt, Michael
AU - Halin, Cornelia
N1 - Funding Information:
The authors acknowledge support of the Scientific Center for Optical and Electron Microscopy (ScopeM) of ETH Zurich, in particular, the help of Szymon Stoma and Simon Nørrelykke. We thank Simone Haener, Nicole Stoffel, Angela Landtwing, and Jasmine Frei (ETH Zurich) for excellent technical assistance and the staff of the ETH Rodent Center HCI for animal husbandry. Moreover, we thank Viola Vogel and Ima Avalos (ETH Zurich) for providing microscope access and precious assistance with flow chamber experiments. The Heisenberg lab (IST Austria), Alexandre Angers-Loustau (University of Helsinki), and the Functional Genomics unit (University of Helsinki) are acknowledged for reagents and protocols. C.H. gratefully acknowledges financial support from the Swiss National Fund (grants 310030_138330 and 310030_156269).
Publisher Copyright:
© 2016 The Authors.
PY - 2016/2/23
Y1 - 2016/2/23
N2 - 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.
AB - 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.
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U2 - 10.1016/j.celrep.2016.01.048
DO - 10.1016/j.celrep.2016.01.048
M3 - Article
C2 - 26876174
AN - SCOPUS:84959113471
SN - 2211-1247
VL - 14
SP - 1723
EP - 1734
JO - Cell Reports
JF - Cell Reports
IS - 7
ER -