Scientists unlock key mechanism for immune cell movement in the body
Scientists from Leeds, Oxford, and Prague have uncovered how immune cells enter the body’s lymphatic system, a breakthrough that could lead to new treatments for autoimmune diseases and cancer.
The body’s immune system is constantly ready to tackle harmful bacteria and viruses. Specialised immune cells known as dendritic cells patrol the body, collecting pieces of microbes and carrying them to lymph nodes, where the immune system processes threats and mounts defences when necessary.
Along the way, dendritic cells need to travel through tiny lymphatic vessels, but until now, scientists haven’t fully understood how these immune cells pass through the vessel walls. Now, a team led by the University of Leeds has discovered how a special receptor on the lymphatic vessel, LYVE-1, plays a key role in this process.
Outlining their findings in a paper published on 20 March in Nature Communications, the team, which included researchers from the School of Physics and Astronomy and School of Biomedical Sciences at Leeds, and partners from the University of Oxford, Europe and the US1, explained how LYVE-1, which lines the entry points of lymphatic vessels, interacts with sugar molecules called hyaluronan that coat the surface of immune cells.
By determining the structure, dynamics, and mechanical properties of molecular complexes of LYVE-1 and hyaluronan, the team discovered that hyaluronan chains can thread themselves through LYVE-1 proteins in a way that allows them to slide back and forth, much like curtains moving along a rail. This sliding motion helps immune cells smoothly squeeze through the lymphatic entry points without getting stuck.
Dr Ralf Richter, who helped lead the study, works between the School of Physics and Astronomy and the School of Biomedical Sciences.
Scientists believe that the new understanding of how immune cells enter the lymphatic system could lead to new treatments for conditions including autoimmune diseases and chronic inflammation, where the immune system mistakenly attacks healthy tissue. Moreover, blocking this mechanism could help prevent cancer cells from spreading through the lymphatic system to other body parts.
Fouzia Bano and Ralf Richter, who led the work at Leeds, said: “Our paper marks a significant advance in understanding how cells enter and migrate through the lymphatics via dedicated receptors and adds to the knowledge of how this relatively neglected vascular network helps orchestrate immune responses.
“Our study also shows the power of a multi-disciplinary approach to science and emphasises the importance of basic research for identifying new therapeutic targets”.
Further information
- 1The complete list of partners on this research include the University of Leeds’ Astbury Centre for Structural Molecular Biology, Bragg Centre for Materials Research, School of Biomedical Sciences, and School of Physics and Astronomy; the University of Oxford, the Czech Academy of Sciences in Prague, the Center for Cooperative Research in Biomaterials, Spain; the University of Oklahoma Health Sciences Center, USA; the University of Bologna, Italy; and the University Grenoble Alpes, France.
- Read the study at Nature Communications.
- For media enquiries, contact Faculty Communications Manager Matt Gardner via M.D.Gardner@leeds.ac.uk.
