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Sixt and colleagues show that, in environments where even the largest pores preclude free passage, leukocytes position their nucleus behind the centrosome and assemble a central F-actin pool that pushes outward to transiently dilate a path for the nucleus.

Sixt, Stein and colleagues show that during T cell migration within lymphatic organs, the chemokine receptor CCR7 quantitatively controls the speed of a continuous actin flow, which is coupled to the environment by the integrin LFA-1.

Podosomes are actin structures important in multiple cell functions. Here, the authors use iPALM microscopy to reveal an “hourglass” shape of the podosome actin core, a protruding “knob” at the bottom of the core, and two actin networks extending from it.

Sixt and colleagues show that different fibroblast populations in the lymph node mechanically control its swelling in a multitier fashion.

Collective motion arises from the coordination of individuals and entails the adjustment of their respective velocities. Yet, how individuals achieve this coordination is often not understood. For migrating cells and motorized agents, Riedl et al. show that the synchronization of the intrinsic oscillator through nearest neighbour coupling establishes the necessary feedback leading to a uniform speed within the collective.

By modulating the presence of lamellipodia and filopodia, Sixt and colleagues determine that migrating dendritic cells rely on these protrusions for directed migration in complex environments, whereas locomotion per se is not driven by lamellipodia.

Current approaches for live imaging of cellular actin dynamics have several drawbacks. Now the use of Lifeact, a 17-aa actin-binding peptide from yeast that is not present in higher eukaryotes, allows imaging of actin dynamics in live mammalian cells without disruption of function and without competition with endogenous binding proteins.

Plasmacytoid dendritic cells monitor the bone marrow for apoptotic megakaryocytes (MKs) and deliver IFNα to the MK niche, triggering local on-demand proliferation and maturation of MK progenitors.

Within three-dimensional environments, leukocytes can migrate even in the complete absence of adhesive forces using the topographical features of the substrate to propel themselves.

Stromal cells in the subcapsular sinus of the lymph node 'decide' which cells and molecules are allowed access to the deeper parenchyma. The glycoprotein PLVAP is a crucial component of this selector function.

During inflammation, lymph nodes swell with an influx of immune cells. New findings identify a signalling pathway that induces relaxation in the contractile cells that give structure to these organs. See Letter p.498

Leukocyte migration over two-dimensional surfaces is dependent on the integrin family of adhesion receptors, which couple the contractile force of the actomyosin cytoskeleton to the extracellular environment. In this study, all integrin heterodimers from mouse leukocytes were ablated and it is shown that integrins are not required for migration in 3D environments, in vitro and in vivo. Such non-adhesive migration renders leukocytes autonomous from the tissue environment.

Boztug and colleagues identify an immunodeficient patient with a deficiency in the guanine-nucleotide-exchange factor RASGRP1. They find that human RASGRP1 is important for the function of T cells, B cells and NK cells and that it has a role in the regulation of the cytoskeleton.

Dendritic cells migrate to and from lymph nodes in response to chemokine gradients.Data now show that steady-state migration of these cells can be triggered by a mechanosensitive pathway.

When cells migrate through complex 3D environments, as are most tissues, they encounter several challenges, including the need to adapt to changing biomechanical properties of the surroundings, squeezing through narrow passages and coordinating motion with other cells. A better understanding of 3D cell migration mechanisms provides key insights into development, tissue regeneration, immune responses and cancer cell dissemination.

Motile cells must navigate complex environments. Here the authors use state-of-the-art imaging, coarse-grained MD simulations and experimental biophysics to show that cells sense their plasma membrane curvature to circumvent obstacles.

Dendritic cells alternate between fast and slow migratory behaviours, however in the absence of a component of the antigen processing machinery, migration is uniform and fast. Chabaudet al. now show that slow migration results from the relocalisation of myosin II to the cell front where it promotes antigen capture.

Knapp and colleagues show that elevated heme levels following hemolysis impair the control of bacterial proliferation by inhibiting phagocytosis and migration of human and mouse phagocytes independently of heme-iron acquisition by bacteria as a source of nutrients.

Yolland et al. demonstrate persistent flow of the actin flow behind the leading edge and its impact on cell directionality during migration.

Geometrically defined microenvironments are used to show that leukocytes migrate along chemokine gradients using the nucleus as a mechanical gauge to sample potential paths and identify the path of least resistance.

Actin polymerization in lamellipodia of cells is regulated by the Arp2/3 complex and FMNL family formins. Here the authors show that both FMNL2 and FMNL3 contribute to lamellipodium protrusion and structure, and abolishing FMNL2/3 reduces protrusion force generation and migration, without affecting Arp2/3 incorporation.

Different muscle cell types account for specific abilities in animals, yet how their diversification arose remains unclear. Here, the authors show that gene duplications of bHLH transcription factors and effector genes contributed to the diversification of muscle cell types in the sea anemone Nematostella.

Leukocytes use different strategies to migrate through the endothelium of venular walls and in interstitial tissues. These strategies are regulated by soluble and cell-bound signals. Studies have identified many of the cellular and subcellular events that govern transendothelial migration and are beginning to elucidate the nature of leukocyte interstitial motility.

Breakdown of vascular barriers is a major complication of inflammatory diseases. However, the mechanisms underlying platelet recruitment to inflammatory micro-environments remains unclear. Here, the authors identify haptotaxis as a key effector function of immune-responsive platelets

Social insects such as ants form a superorganism in which individual colony members cooperate for disease defence, much like the cells of an organism. Studying social insect colonies can help to determine common principles that unite the disease defences of organisms, superorganisms and societies.

Honey bee workers take on different tasks for the colony as they age. Here, the authors develop a method to extract a descriptor of the individuals’ social networks and show that interaction patterns predict task allocation and distinguish different developmental trajectories.

Migrating dendritic cells can adapt their adhesive properties to switch between integrin-dependent and -independent modes of migration. By modulating their actin polymerization dynamics, cells can maintain a steady migration speed through a changing environment.

Kindlin-3 interacts with β₁ and β₃ integrins on platelets, and Kindlin-3–deficient mice have defects in platelet activation and blood clotting. Moser et al. now show that these mice also have defects in β₂ integrin activation on leukocytes, leading to severely compromised leukocyte adhesion to the endothelium. The combined platelet and leukocyte defects of these mice resemble those seen in individuals with the leukocyte adhesion deficiency syndrome LAD-III. Other papers in this issue by Malinin et al. and Svensson et al. provide evidence that KINDLIN-3 dysfunction does indeed underlie this type of human disease syndrome (pages 249–250, 306–312 and 313–318).

The authors identify a new tumor suppressor role for Smurf2 that is linked to its regulation of histone modifications through RNF20. In the absence of Smurf2 in mice, and potentially also when its nuclear function is compromised in human tumors, higher levels of histone ubiquitination lead to a relaxation of chromatin structure, and alterations in DNA repair result in compromised genomic instability and increased tumorigenesis in aging mice. The findings suggest that loss of Smurf2 function may underlie tumor initiation by reshaping the epigenetic landscape of cells.

The recirculation of lymphocytes through lymph nodes and their encounter with dendritic cells is crucial for immunity. Here, the authors review the role of high endothelial venules, lymphatics and lymph node stroma in the trafficking of immune cells in lymph nodes during homeostasis.

Homologous recombination is crucial for genome stability and for genetic exchange. Our knowledge of homology search, the step in this process that explores the genome for homologous sequences to enable recombination, has been increased by recent methodological advances. These insights can be integrated into a mechanistic model of homology search.

In this Review, the authors discuss the molecular mechanisms that enable B cells to internalize, process and present antigens on MHC class II molecules to CD4⁺T cells. They focus on the importance of cytoskeletal rearrangements and the establishment of polarity in B cells for these processes.