Slow integrin-dependent migration organizes networks of tissue-resident mast cells

Many leukocytes use fast and flexible amoeboid migration strategies to move autonomously throughout tissues. Here, we show that the movement of mast cells (MCs), leukocytes with important roles during allergies and anaphylaxis, fundamentally differs from this rapid adhesion-free leukocyte migration. We identify a crucial role for integrin-dependent adhesion in controlling slow MC movement, which shapes the positioning and network-like tissue distribution of this long-lived immune cell type. In contrast to other immune and non-immune cells, MCs cannot compensate for the lack of integrin function by switching to another migration mode. Single-cell RNA-sequencing revealed a special role for integrins in defining a mature MC phenotype in the periarteriolar tissue space where several stromal cell types provide an anatomical niche rich in Kit ligand, the major MC growth and survival factor. Collectively, this study highlights substrate-dependent haptokinesis as an important mechanism for MC network formation and the tissue organization of resident immune cells.