Immune cell locomotion is associated with amoeboid migration, a flexible mode of movement, which depends on rapid cycles of actin polymerization and actomyosin contraction1. Many immune cells do not necessarily require integrins, the major family of adhesion receptors in mammals, to move productively through three-dimensional tissue spaces2,3. Instead, they can use alternative strategies to transmit their actin-driven forces to the substrate, explaining their migratory adaptation to changing external environments4-6. However, whether these generalized concepts apply to all immune cells is unclear. Here, we show that the movement of mast cells (immune cells with important roles during allergy and anaphylaxis) differs fundamentally from the widely applied paradigm of interstitial immune cell migration. We identify a crucial role for integrin-dependent adhesion in controlling mast cell movement and localization to anatomical niches rich in KIT ligand, the major mast cell growth and survival factor. Our findings show that substrate-dependent haptokinesis is an important mechanism for the tissue organization of resident immune cells.
© 2023. The Author(s).

The mechanical properties of the extracellular environment emerge as critical regulators of cellular functions. Cell mechanotransduction is mainly studied in vitro at initial stages of cell adhesion and very little is known about the mechanoresponses of cells with established tensional dynamics, resembling cells embedded in tissues. Here, we provide in vivo evidence that talin-dependent cell-matrix adhesions are global regulators of vascular mechanics and establish talin as an essential and required mechanosensor in neovessels and already developed tumours. At the molecular level, we demonstrate that talin exploits alternative mechanisms to dynamically-adjust the mechanical integrity of endothelial cells. Our mutational studies indicate a previously unknown role for the requirement of the talin-head in mechanosensing and demonstrate that the talin-head and the talin-rod alone are sufficient to maintain mechanical stability of endothelial cells. Overall, our results underpin the significance of mechanical signals in regulating vascular morphology in steady-state conditions and ultimately modulate cancer progression. Talin mechanosensing is required to maintain cell morphology and control developmental and tumour angiogenesis.

Macrophages are key immune cells with important roles for tissue surveillance in almost all mammalian organs. Cellular networks made up of many individual macrophages allow for optimal removal of dead cell material and pathogens in tissues. However, the critical determinants that underlie these population responses have not been systematically studied. Here, we investigated how cell shape and the motility of individual cells influences macrophage network responses in 3D culture settings and in mouse tissues. We show that surveying macrophage populations can tolerate lowered actomyosin contractility, but cannot easily compensate for a lack of integrin-mediated adhesion. Although integrins were dispensable for macrophage chemotactic responses, they were crucial to control cell movement and protrusiveness for optimal surveillance by a macrophage population. Our study reveals that β1 integrins are important for maintaining macrophage shape and network sampling efficiency in mammalian tissues, and sets macrophage motility strategies apart from the integrin-independent 3D migration modes of many other immune cell subsets.
© 2022, Paterson and Lämmermann.

In humans, parity without breastfeeding increases risk of estrogen receptor-negative (ER-) breast cancer and is associated with hypermethylation of FOXA1, a pioneer factor regulating lineage commitment of mammary gland luminal progenitor cells. We postulate that pregnancy-associated repression of FOXA1 results in the accumulation of aberrant, differentiation-arrested luminal progenitor cells which, following additional genetic and epigenetic insults, may give rise to ER- tumors. Consistent with this hypothesis, we show that deletion of Foxa1 in the mouse mammary gland results in a two-fold increase in the proportion of luminal progenitor cells and a reduction in mammary gland epithelial cells that stain positive for ER. These results provide compelling support for the notion that reduced Foxa1 expression is sufficient to alter mammary gland luminal cell fate determination in vivo, which could be a mechanism linking parity with ER- breast cancer.
AJCR Copyright © 2021.

Itgb3‑integrin‑deficient (Itgb3‑/‑) mice have been reported as a Glanzmann thrombasthenia (GT) model and have been used for platelet research. However, it remains unclear whether this mouse model can fully simulate patients with GT or whether it has different characteristics from these patients. The present study aimed to answer this question. Itgb3‑/‑ mice were tested for platelet function, tail bleeding, whole‑blood count, bone marrow hematopoiesis and organ enlargement. Itgb3‑/‑ platelets showed impaired functions, including fibrinogen binding, aggregation, adhesion or spreading. Itgb3‑/‑ mice demonstrated decreased platelet count and microcytic hypochromic anemia. Reduced iron staining of bone marrow and decreased plasma ferritin level confirmed the diagnosis of iron deficiency anemia. Evident splenomegaly was observed in Itgb3‑/‑ mice. Immunohistochemical analysis of spleen biopsy revealed normal expression of CD3 and CD19, but elevated expression of CD71, which suggested that the splenomegaly in Itgb3‑/‑ mice may be associated with extramedullary hematopoiesis. In conclusion, Itgb3‑/‑ mice exhibited some unique characteristics that differed from those of human patients with GT and thus cannot completely simulate patients with GT.