Department of Cell and Molecular Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA.
Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, University of Rochester Medical Center, Rochester, NY, USA.
J Cell Biol. 2024 Oct 7;223(10). doi: 10.1083/jcb.202310067. Epub 2024 Jun 18.
Immune cells are highly dynamic and able to migrate through environments with diverse biochemical and mechanical compositions. Their migration has classically been defined as amoeboid under the assumption that it is integrin independent. Here, we show that activated primary Th1 T cells require both confinement and extracellular matrix proteins to migrate efficiently. This migration is mediated through small and dynamic focal adhesions that are composed of the same proteins associated with canonical mesenchymal cell focal adhesions, such as integrins, talin, and vinculin. These focal adhesions, furthermore, localize to sites of contractile traction stresses, enabling T cells to pull themselves through confined spaces. Finally, we show that Th1 T cells preferentially follow tracks of other T cells, suggesting that these adhesions modify the extracellular matrix to provide additional environmental guidance cues. These results demonstrate not only that the boundaries between amoeboid and mesenchymal migration modes are ambiguous, but that integrin-mediated focal adhesions play a key role in T cell motility.
免疫细胞具有高度的动态性,能够在具有不同生化和力学组成的环境中迁移。它们的迁移传统上被定义为变形虫样,假设它与整合素无关。在这里,我们表明激活的原始 Th1 T 细胞需要限制和细胞外基质蛋白才能有效地迁移。这种迁移是通过小而动态的焦点粘连介导的,这些焦点粘连由与经典间充质细胞焦点粘连相关的相同蛋白组成,例如整合素、talin 和 vinculin。此外,这些焦点粘连定位于收缩牵引力的部位,使 T 细胞能够穿过受限空间。最后,我们表明 Th1 T 细胞优先遵循其他 T 细胞的轨迹,这表明这些粘连改变细胞外基质以提供额外的环境引导线索。这些结果不仅表明变形虫样和间充质样迁移模式之间的界限是模糊的,而且表明整合素介导的焦点粘连在 T 细胞迁移中起着关键作用。