In a study published in Nature Immunology, researchers from the Sixt group at the Institute of Science and Technology Austria (ISTA) have shown how dendritic cells use their cytoskeleton to move through the body’s complex, three-dimensional tissues. These immune cells, which search for pathogens in tissues such as the skin and migrate to the lymph nodes on contact with them to trigger an immune response, are the focus of the study.

The cells navigate through tissue by forming a lamellipodium, an actin-based structure at their front that controls forward movement. At the same time, they use their nucleus to explore accessible pathways. In confined spaces, dendritic cells deploy a central actin structure that pushes obstacles sideways to create passages without damaging the tissue with enzymes, as other cells do. This coordination between forward and lateral forces is crucial for movement.

The study shows that cells without the protein DOCK8, which is missing due to mutations in a rare immune disease, cannot form a central actin structure. This leads to severe migration defects as the cells get stuck in tight spaces or form uncontrolled protrusions that can elongate and even destroy them. These findings clarify why DOCK8 mutations lead to recurrent infections and skin problems and shed light on a new mechanism of cell movement that is essential for the immune response.

The project was supported by funding from the European Research Council, an HFSP postdoctoral fellowship and a Lise Meitner fellowship from the Austrian Science Fund.

Original Paper:

Migrating immune cells globally coordinate protrusive forces | Nature Immunology

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