article published yes Jonna H Alanko author 2CC12E8C-F248-11E8-B48F-1D18A9856A870000-0002-7698-3061 Mehmet C Ucar author 50B2A802-6007-11E9-A42B-EB23E66974250000-0003-0506-4217 Nikola Canigova author 3795523E-F248-11E8-B48F-1D18A9856A870000-0002-8518-5926 Julian A Stopp author 489E3F00-F248-11E8-B48F-1D18A9856A87 Jan Schwarz author 346C1EC6-F248-11E8-B48F-1D18A9856A87 Jack Merrin author 4515C308-F248-11E8-B48F-1D18A9856A870000-0001-5145-4609 Edouard B Hannezo author 3A9DB764-F248-11E8-B48F-1D18A9856A870000-0001-6005-1561 Michael K Sixt author 41E9FBEA-F248-11E8-B48F-1D18A9856A870000-0002-6620-9179 MiSi department EdHa department NanoFab department Cellular Navigation Along Spatial Gradients project Design Principles of Branching Morphogenesis project Nano-Analytics of Cellular Systems project ISTplus - Postdoctoral Fellowships project Immune responses rely on the rapid and coordinated migration of leukocytes. Whereas it is well established that single-cell migration is often guided by gradients of chemokines and other chemoattractants, it remains poorly understood how these gradients are generated, maintained, and modulated. By combining experimental data with theory on leukocyte chemotaxis guided by the G protein–coupled receptor (GPCR) CCR7, we demonstrate that in addition to its role as the sensory receptor that steers migration, CCR7 also acts as a generator and a modulator of chemotactic gradients. Upon exposure to the CCR7 ligand CCL19, dendritic cells (DCs) effectively internalize the receptor and ligand as part of the canonical GPCR desensitization response. We show that CCR7 internalization also acts as an effective sink for the chemoattractant, dynamically shaping the spatiotemporal distribution of the chemokine. This mechanism drives complex collective migration patterns, enabling DCs to create or sharpen chemotactic gradients. We further show that these self-generated gradients can sustain the long-range guidance of DCs, adapt collective migration patterns to the size and geometry of the environment, and provide a guidance cue for other comigrating cells. Such a dual role of CCR7 as a GPCR that both senses and consumes its ligand can thus provide a novel mode of cellular self-organization. American Association for the Advancement of Science2023 eng General MedicineImmunology 2470-9468 37656776 00106211060000310.1126/sciimmunol.adc9584 887 https://research-explorer.ista.ac.at/record/14279 https://research-explorer.ista.ac.at/record/14697 https://research-explorer.ista.ac.at/record/19745 Alanko, Jonna H, Mehmet C Ucar, Nikola Canigova, Julian A Stopp, Jan Schwarz, Jack Merrin, Edouard B Hannezo, and Michael K Sixt. “CCR7 Acts as Both a Sensor and a Sink for CCL19 to Coordinate Collective Leukocyte Migration.” <i>Science Immunology</i>. American Association for the Advancement of Science, 2023. <a href="https://doi.org/10.1126/sciimmunol.adc9584">https://doi.org/10.1126/sciimmunol.adc9584</a>. J. H. Alanko <i>et al.</i>, “CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration,” <i>Science Immunology</i>, vol. 8, no. 87. American Association for the Advancement of Science, 2023. Alanko JH, Ucar MC, Canigova N, Stopp JA, Schwarz J, Merrin J, Hannezo EB, Sixt MK. 2023. CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration. Science Immunology. 8(87), adc9584. Alanko JH, Ucar MC, Canigova N, et al. CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration. <i>Science Immunology</i>. 2023;8(87). doi:<a href="https://doi.org/10.1126/sciimmunol.adc9584">10.1126/sciimmunol.adc9584</a> J.H. Alanko, M.C. Ucar, N. Canigova, J.A. Stopp, J. Schwarz, J. Merrin, E.B. Hannezo, M.K. Sixt, Science Immunology 8 (2023). Alanko, J. H., Ucar, M. C., Canigova, N., Stopp, J. A., Schwarz, J., Merrin, J., … Sixt, M. K. (2023). CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration. <i>Science Immunology</i>. American Association for the Advancement of Science. <a href="https://doi.org/10.1126/sciimmunol.adc9584">https://doi.org/10.1126/sciimmunol.adc9584</a> Alanko, Jonna H., et al. “CCR7 Acts as Both a Sensor and a Sink for CCL19 to Coordinate Collective Leukocyte Migration.” <i>Science Immunology</i>, vol. 8, no. 87, adc9584, American Association for the Advancement of Science, 2023, doi:<a href="https://doi.org/10.1126/sciimmunol.adc9584">10.1126/sciimmunol.adc9584</a>. 142742023-09-06T08:07:51Z2026-10-16T22:30:34Z