Mechanosensitive ACKR4 scavenges CCR7 chemokines to facilitate T cell de-adhesion and passive transport by flow in inflamed afferent lymphatics

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2022
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Friess, Mona C.
Kritikos, Ioannis
Schineis, Philipp
Medina-Sanchez, Jessica Danielly
Gkountidi, Anastasia-Olga
Vallone, Angela
Sigmund, Elena C.
Halin, Cornelia
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Cell Reports. Cell Press. 2022, 38(5), 110334. eISSN 2211-1247. Available under: doi: 10.1016/j.celrep.2022.110334
Zusammenfassung

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.

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ISO 690FRIESS, Mona C., Ioannis KRITIKOS, Philipp SCHINEIS, Jessica Danielly MEDINA-SANCHEZ, Anastasia-Olga GKOUNTIDI, Angela VALLONE, Elena C. SIGMUND, Christoph MATTI, Daniel F. LEGLER, Cornelia HALIN, 2022. Mechanosensitive ACKR4 scavenges CCR7 chemokines to facilitate T cell de-adhesion and passive transport by flow in inflamed afferent lymphatics. In: Cell Reports. Cell Press. 2022, 38(5), 110334. eISSN 2211-1247. Available under: doi: 10.1016/j.celrep.2022.110334
BibTex
@article{Friess2022-02-01Mecha-56477,
  year={2022},
  doi={10.1016/j.celrep.2022.110334},
  title={Mechanosensitive ACKR4 scavenges CCR7 chemokines to facilitate T cell de-adhesion and passive transport by flow in inflamed afferent lymphatics},
  number={5},
  volume={38},
  journal={Cell Reports},
  author={Friess, Mona C. and Kritikos, Ioannis and Schineis, Philipp and Medina-Sanchez, Jessica Danielly and Gkountidi, Anastasia-Olga and Vallone, Angela and Sigmund, Elena C. and Matti, Christoph and Legler, Daniel F. and Halin, Cornelia},
  note={Article Number: 110334}
}
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