Migration of dendritic cells: physical principles, molecular mechanisms, and functional implications

Abstract

Dendritic cells (DCs) constitute a complex cell population that resides in both peripheral tissues and lymphoid organs. Their major function in tissues is to patrol their environment in search of danger-associated antigens to transport to lymph nodes and present to T lymphocytes. This process constitutes the first step of the adaptive immune response and relies on specific DC properties, including a high endocytic capacity as well as efficient motility in confined three-dimensional environments. Although cell motility has been widely studied, little is known on how the geometric characteristics of the environment influence DC migration and function. In this review, we give an overview of the basic physical principles and molecular mechanisms that control DC migration under confinement and discuss how such mechanisms impact the environment-patrolling capacity of DCs.

Actin Flows Mediate a Universal Coupling between Cell Speed and Cell Persistence

“…It is possible that some cells regulate binding of polarity factors to actin to tune their persistence. Making use of recent results that identified optimal search patterns for both persistent (Tejedor et al, 2012) and intermittent trajectories , we anticipate that the search efficiency for a target (e.g., DCs searching for antigens in a tissue) (Heuzé et al, 2013) could be optimized by tuning b and C s . The model we propose thus provides a very generic ingredient of cell migration that could be used as a basis to model any process in which individual cell trajectories matter, such as search processes by immune cells (Harris et al, 2012), neuronal cells migration, or invasion by cancer cells.…”

The multiple faces of leukocyte interstitial migration

“…In combination with microfluidics, these microchannels now also allow dissecting how chemokine gradient sensing, physical constraints, and fluid flow together influence leukocyte guidance [46–48]. Since the stiffness and texture of the environment are additional parameters affecting cell migration, researchers have begun to develop confined environments with elastic walls [49] and asymmetric features [50], in the form of micropillars [51] or structured nanopatterns [52]. While almost any structure, texture, and geometry seems technically feasible, such reductionist microfabricated devices will be most useful when wisely chosen to mimic a particular physiological aspect of leukocyte tissue migration.…”

Tailored immunity by skin antigen-presenting cells

“…To do so, they exhibit unique physical properties that allow them to migrate through confined space such as lymphatics. 18 Upon inflammation, resident LCs drastically change in morphology and motility and increase their expression of CCR7, which ligands CCL19 and CCL21 are constitutively expressed by endothelial cells of the lymphatic vessels. 19 This phenomenon, largely mediated by cytokines of the IL-1 family and TNF-α produced by keratinocytes, has to overcome the autocrine effect of tumor growth factor (TGF)-β, which by upregulating E-cadherin and downregulating CCR7 promotes LC retention in the skin.…”