Friess, Mona C; Kritikos, Ioannis; Schineis, Philipp; Medina-Sanchez, Jessica Danielly; Gkountidi, Anastasia-Olga; Vallone, Angela; Sigmund, Elena C; Schwitter, Corina; Vranova, Martina; Matti, Christoph; Arasa, Jorge; Saygili Demir, Cansaran; Bovay, Esther; Proulx, Steven T; Tomura, Michio; Rot, Antal; Legler, Daniel F; Petrova, Tatiana V; Halin, Cornelia (2022). Mechanosensitive ACKR4 scavenges CCR7 chemokines to facilitate T cell de-adhesion and passive transport by flow in inflamed afferent lymphatics. Cell reports, 38(5), p. 110334. Cell Press 10.1016/j.celrep.2022.110334
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T cell migration via afferent lymphatics to draining lymph nodes (dLNs) depends on expression of CCR7 in T cells and CCL21 in the lymphatic vasculature. Once T cells have entered lymphatic capillaries, they slowly migrate into contracting collecting vessels. Here, lymph flow picks up, inducing T cell detachment and rapid transport to the dLNs. We find that the atypical chemokine receptor 4 (ACKR4), which binds and internalizes CCL19 and CCL21, is induced by lymph flow in endothelial cells lining lymphatic collectors, enabling them to scavenge these chemokines. In the absence of ACKR4, migration of T cells to dLNs in TPA-induced inflammation is significantly reduced. While entry into capillaries is not impaired, T cells accumulate in the ACKR4-deficient dermal collecting vessel segments. Overall, our findings identify an ACKR4-mediated mechanism by which lymphatic collectors facilitate the detachment of lymph-borne T cells in inflammation and their transition from crawling to free-flow toward the dLNs.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute |
UniBE Contributor: |
Proulx, Steven Thomas, Legler, Daniel |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2211-1247 |
Publisher: |
Cell Press |
Language: |
English |
Submitter: |
Andrea Stettler |
Date Deposited: |
20 Dec 2022 14:48 |
Last Modified: |
20 Dec 2022 18:39 |
Publisher DOI: |
10.1016/j.celrep.2022.110334 |
PubMed ID: |
35108538 |
Uncontrolled Keywords: |
ACKR4 CCL21, CCL19 T cell migration afferent lymphatics chemokine scavenging collecting vessels de-adhesion lymph flow mechanosensing |
BORIS DOI: |
10.48350/176210 |
URI: |
https://boris.unibe.ch/id/eprint/176210 |
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