Mechanosensitive ACKR4 scavenges CCR7 chemokines to facilitate T cell de-adhesion and passive transport by flow in inflamed afferent lymphatics
| Autor: | Mona C. Friess, Ioannis Kritikos, Philipp Schineis, Jessica Danielly Medina-Sanchez, Anastasia-Olga Gkountidi, Angela Vallone, Elena C. Sigmund, Corina Schwitter, Martina Vranova, Christoph Matti, Jorge Arasa, Cansaran Saygili Demir, Esther Bovay, Steven T. Proulx, Michio Tomura, Antal Rot, Daniel F. Legler, Tatiana V. Petrova, Cornelia Halin |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Receptors
CCR7 ACKR4 T-Lymphocytes 610 Medicine & health T cell migration General Biochemistry Genetics and Molecular Biology Mice Receptors CCR Mechanosensing Cell Movement ddc:570 CCL19 Animals Humans Lymph flow Afferent lymphatics De-adhesion Collecting vessels Chemokine scavenging CCL21 Lymphatic Vessels Skin Inflammation integumentary system Endothelial Cells Dendritic Cells Lymph Nodes |
| Zdroj: | Cell Reports, 38 (5) 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 |
| ISSN: | 2666-3864 2211-1247 |
| Popis: | 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. Cell Reports, 38 (5) ISSN:2666-3864 ISSN:2211-1247 |
| Databáze: | OpenAIRE |
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