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

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.

[1]  P. Preira,et al.  Passive circulating cell sorting by deformability using a microfluidic gradual filter. , 2013, Lab on a chip.

[2]  P. Sly,et al.  Accelerated Antigen Sampling and Transport by Airway Mucosal Dendritic Cells following Inhalation of a Bacterial Stimulus1 , 2006, The Journal of Immunology.

[3]  J. Klafter,et al.  First-passage times in complex scale-invariant media , 2007, Nature.

[4]  A. Prescott,et al.  Enhanced Dendritic Cell Antigen Capture via Toll-Like Receptor-Induced Actin Remodeling , 2004, Science.

[5]  A. Rudensky,et al.  Distinct dendritic cell populations sequentially present antigen to CD4 T cells and stimulate different aspects of cell-mediated immunity. , 2003, Immunity.

[6]  H. Stone,et al.  Cellular-scale hydrodynamics , 2008, Biomedical materials.

[7]  Matthieu Piel,et al.  Cell migration in confinement: a micro-channel-based assay. , 2011, Methods in molecular biology.

[8]  S. Lira,et al.  Luminal bacteria recruit CD103+ dendritic cells into the intestinal epithelium to sample bacterial antigens for presentation. , 2013, Immunity.

[9]  Michael Sixt,et al.  Interstitial Dendritic Cell Guidance by Haptotactic Chemokine Gradients , 2013, Science.

[10]  P. Perrin,et al.  Dynamics and function of Langerhans cells in vivo: dermal dendritic cells colonize lymph node areas distinct from slower migrating Langerhans cells. , 2005, Immunity.

[11]  Guillaume Charras,et al.  Blebs lead the way: how to migrate without lamellipodia , 2008, Nature Reviews Molecular Cell Biology.

[12]  Henrik Flyvbjerg,et al.  Cell motility as persistent random motion: theories from experiments. , 2005, Biophysical journal.

[13]  L. Fetler,et al.  Do cancer cells have distinct adhesions in 3D collagen matrices and in vivo? , 2012, European Journal of Cell Biology.

[14]  C. Sasakawa,et al.  Intestinal villous M cells: an antigen entry site in the mucosal epithelium. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[15]  C. Figdor,et al.  A Critical Role for Prostaglandin E2 in Podosome Dissolution and Induction of High-Speed Migration during Dendritic Cell Maturation1 , 2006, The Journal of Immunology.

[16]  O Bénichou,et al.  Two-dimensional intermittent search processes: An alternative to Lévy flight strategies. , 2006, Physical review. E, Statistical, nonlinear, and soft matter physics.

[17]  Miguel Vicente-Manzanares,et al.  Cutting Edge: Association of the Motor Protein Nonmuscle Myosin Heavy Chain-IIA with the C Terminus of the Chemokine Receptor CXCR4 in T Lymphocytes1 , 2002, The Journal of Immunology.

[18]  K. Magnusson,et al.  Neutrophil leukocyte motility requires directed water influx , 2002, Journal of leukocyte biology.

[19]  D. Hammer,et al.  Hematopoietic Lineage Cell-Specific Protein 1 Functions in Concert with the Wiskott–Aldrich Syndrome Protein To Promote Podosome Array Organization and Chemotaxis in Dendritic Cells , 2011, The Journal of Immunology.

[20]  Claudio G. Rolli,et al.  Impact of Tumor Cell Cytoskeleton Organization on Invasiveness and Migration: A Microchannel-Based Approach , 2010, PloS one.

[21]  Yue Sun,et al.  Movin' on up: the role of PtdIns(4,5)P(2) in cell migration. , 2006, Trends in cell biology.

[22]  W. Lim,et al.  The first World Cell Race , 2012, Current Biology.

[23]  Marion Ghibaudo,et al.  Mechanics of cell spreading within 3D-micropatterned environments. , 2011, Lab on a chip.

[24]  Joachim P Spatz,et al.  Immobilized chemokine fields and soluble chemokine gradients cooperatively shape migration patterns of dendritic cells. , 2009, Immunity.

[25]  V. Kuchroo,et al.  Podoplanin-Rich Stromal Networks Induce Dendritic Cell Motility via Activation of the C-type Lectin Receptor CLEC-2 , 2012, Immunity.

[26]  R. Germain,et al.  Dynamic imaging of dendritic cell extension into the small bowel lumen in response to epithelial cell TLR engagement , 2006, The Journal of experimental medicine.

[27]  Pierre Bongrand,et al.  Microfluidic investigation reveals distinct roles for actin cytoskeleton and myosin II activity in capillary leukocyte trafficking. , 2009, Biophysical journal.

[28]  S. Malawista,et al.  Chemotaxis by human neutrophils and their cytokineplasts treated with inhibitors of nitric oxide synthase: no suppression of orientation or trajectory , 1997, Journal of leukocyte biology.

[29]  Miki Y. Matsuo,et al.  Ordered Patterns of Cell Shape and Orientational Correlation during Spontaneous Cell Migration , 2008, PloS one.

[30]  Mehmet Toner,et al.  Burn Injury Reduces Neutrophil Directional Migration Speed in Microfluidic Devices , 2010, PloS one.

[31]  T. Bretschneider,et al.  Formins and VASPs may co-operate in the formation of filopodia. , 2005, Biochemical Society transactions.

[32]  T. Jin,et al.  An Elmo-like protein associated with myosin II restricts spurious F-actin events to coordinate phagocytosis and chemotaxis. , 2008, Developmental cell.

[33]  K. Beningo,et al.  Responses of fibroblasts to anchorage of dorsal extracellular matrix receptors , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[34]  O Bénichou,et al.  Optimal search strategies for hidden targets. , 2005, Physical review letters.

[35]  A. Callan-Jones,et al.  Active gel model of amoeboid cell motility , 2013, 1301.7562.

[36]  O. Destaing,et al.  Actin machinery and mechanosensitivity in invadopodia, podosomes and focal adhesions , 2009, Journal of Cell Science.

[37]  M. Sixt,et al.  Cdc42-dependent leading edge coordination is essential for interstitial dendritic cell migration. , 2009, Blood.

[38]  Moon Jeong Park,et al.  Nanotopography-Guided Migration of T Cells , 2012, The Journal of Immunology.

[39]  B. Malissen,et al.  Pathogenic bacteria and dead cells are internalized by a unique subset of Peyer's patch dendritic cells that express lysozyme. , 2010, Gastroenterology.

[40]  F. Ginhoux,et al.  Origin and functional heterogeneity of non‐lymphoid tissue dendritic cells in mice , 2010, Immunological reviews.

[41]  C. Figdor,et al.  Interplay between myosin IIA-mediated contractility and actin network integrity orchestrates podosome composition and oscillations , 2013, Nature Communications.

[42]  Rodney D. Newberry,et al.  Goblet cells deliver luminal antigen to CD103+ DCs in the small intestine , 2012, Nature.

[43]  K. Magnusson,et al.  Water flux in cell motility: expanding the mechanisms of membrane protrusion. , 2009, Cell motility and the cytoskeleton.

[44]  J. R. Chubb,et al.  The Dictyostelium RasS protein is required for macropinocytosis, phagocytosis and the control of cell movement. , 2000, Journal of cell science.

[45]  Richard A. Firtel,et al.  Rap1 controls cell adhesion and cell motility through the regulation of myosin II , 2007, The Journal of cell biology.

[46]  A. Blangy,et al.  Cofilin Activation during Podosome Belt Formation in Osteoclasts , 2012, PloS one.

[47]  L. Addadi,et al.  Nano-topography sensing by osteoclasts , 2010, Journal of Cell Science.

[48]  Matthieu Piel,et al.  Microfabricated devices for cell biology: all for one and one for all. , 2013, Current opinion in cell biology.

[49]  J. Spatz,et al.  Adaptive force transmission in amoeboid cell migration , 2009, Nature Cell Biology.

[50]  C. Vieu,et al.  Dynamics of podosome stiffness revealed by atomic force microscopy , 2010, Proceedings of the National Academy of Sciences.

[51]  G. Gundersen,et al.  Nuclear Movement Regulated by Cdc42, MRCK, Myosin, and Actin Flow Establishes MTOC Polarization in Migrating Cells , 2005, Cell.

[52]  Steffen Jung,et al.  Securing the immune tightrope: mononuclear phagocytes in the intestinal lamina propria , 2010, Nature Reviews Immunology.

[53]  Olivier Bénichou,et al.  Optimizing persistent random searches. , 2011, Physical review letters.

[54]  Stefan Schinkinger,et al.  The regulatory role of cell mechanics for migration of differentiating myeloid cells , 2009, Proceedings of the National Academy of Sciences.

[55]  F. Powrie,et al.  Small intestinal CD103+ dendritic cells display unique functional properties that are conserved between mice and humans , 2008, The Journal of experimental medicine.

[56]  Matthieu Piel,et al.  Regulation of Dendritic Cell Migration by CD74, the MHC Class II-Associated Invariant Chain , 2008, Science.

[57]  Philippe Bousso,et al.  Dynamic in situ cytometry uncovers T cell receptor signaling during immunological synapses and kinapses in vivo. , 2012, Immunity.

[58]  Steffen Jung,et al.  Intestinal lamina propria dendritic cell subsets have different origin and functions. , 2009, Immunity.

[59]  P. Ricciardi-Castagnoli,et al.  Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria , 2001, Nature Immunology.

[60]  N. Carragher,et al.  Inhibition of calpain stabilises podosomes and impairs dendritic cell motility , 2006, Journal of Cell Science.

[61]  A. Prescott,et al.  A role for ARF6 in dendritic cell podosome formation and migration , 2008, European journal of immunology.

[62]  Steffen Jung,et al.  Transepithelial Pathogen Uptake into the Small Intestinal Lamina Propria1 , 2006, The Journal of Immunology.

[63]  原田 洋輔 DOCK8 is a Cdc42 activator critical for interstitial dendritic cell migration during immune responses , 2013 .

[64]  R. Buettner,et al.  Four-and-a-Half LIM Domain Protein 2 Is a Novel Regulator of Sphingosine 1-Phosphate Receptor 1 in CCL19-Induced Dendritic Cell Migration , 2010, The Journal of Immunology.

[65]  H. Spaink,et al.  A spatially restricted increase in receptor mobility is involved in directional sensing during Dictyostelium discoideum chemotaxis , 2008, Journal of Cell Science.

[66]  M. Piel,et al.  Confinement-Optimized 3-Dimensional T cell Amoeboid Motility is Modulated via Myosin IIA-Regulated Adhesions , 2010, Nature Immunology.

[67]  E. Fama,et al.  Migration , 2007 .

[68]  C. Brakebusch,et al.  Rho-Family GTPase Cdc42 Controls Migration of Langerhans Cells In Vivo , 2013, The Journal of Immunology.

[69]  T. Blankenstein,et al.  CCR7 governs skin dendritic cell migration under inflammatory and steady-state conditions. , 2004, Immunity.

[70]  M. Sixt,et al.  Rapid leukocyte migration by integrin-independent flowing and squeezing , 2008, Nature.

[71]  W. Agace,et al.  Intestinal CD103+, but not CX3CR1+, antigen sampling cells migrate in lymph and serve classical dendritic cell functions , 2009, The Journal of experimental medicine.

[72]  Marcus L. Roper,et al.  Microscopic artificial swimmers , 2005, Nature.

[73]  Jacco van Rheenen,et al.  Tissue-resident memory CD8+ T cells continuously patrol skin epithelia to quickly recognize local antigen , 2012, Proceedings of the National Academy of Sciences.

[74]  T. Kepler,et al.  Selective and site-specific mobilization of dermal dendritic cells and Langerhans cells by Th1- and Th2-polarizing adjuvants , 2010, Proceedings of the National Academy of Sciences.

[75]  S. Malawista,et al.  Random locomotion and chemotaxis of human blood polymorphonuclear leukocytes (PMN) in the presence of EDTA: PMN in close quarters require neither leukocyte integrins nor external divalent cations. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[76]  Han Wei Hou,et al.  Deformability based cell margination--a simple microfluidic design for malaria-infected erythrocyte separation. , 2010, Lab on a chip.

[77]  O. Bénichou,et al.  Spontaneous contractility-mediated cortical flow generates cell migration in three-dimensional environments. , 2010, Biophysical journal.

[78]  L. Preziosi,et al.  A Cellular Potts Model simulating cell migration on and in matrix environments. , 2012, Mathematical biosciences and engineering : MBE.

[79]  T. Jin,et al.  A shortcut from GPCR signaling to Rac-mediated actin cytoskeleton through an ELMO/DOCK complex , 2012, Small GTPases.

[80]  Hugues Lelouard,et al.  Peyer's patch dendritic cells sample antigens by extending dendrites through M cell-specific transcellular pores. , 2012, Gastroenterology.

[81]  Samantha J. Hardy,et al.  Impaired dendritic-cell homing in vivo in the absence of Wiskott-Aldrich syndrome protein. , 2005, Blood.

[82]  Alberto Diaspro,et al.  Endocytic Trafficking of Rac Is Required for the Spatial Restriction of Signaling in Cell Migration , 2008, Cell.

[83]  M. Sixt,et al.  Preformed portals facilitate dendritic cell entry into afferent lymphatic vessels , 2009, The Journal of experimental medicine.

[84]  D. Tough,et al.  Developmental kinetics and lifespan of dendritic cells in mouse lymphoid organs. , 2002, Blood.

[85]  J. Joanny,et al.  Pushing off the walls: a mechanism of cell motility in confinement. , 2009, Physical review letters.

[86]  Klemens Rottner,et al.  Filopodia formation in the absence of functional WAVE- and Arp2/3-complexes. , 2006, Molecular biology of the cell.

[87]  T. Svitkina,et al.  The signaling adaptor Eps8 is an essential actin capping protein for dendritic cell migration. , 2011, Immunity.

[88]  Hidde L Ploegh,et al.  CX3CR1-Mediated Dendritic Cell Access to the Intestinal Lumen and Bacterial Clearance , 2005, Science.

[89]  M. Moreau,et al.  Intermittent search strategies , 2011, 1104.0639.

[90]  Donna J. Webb,et al.  New dimensions in cell migration , 2003, Nature Cell Biology.

[91]  E. Volpe,et al.  The human cytokine TSLP triggers a cell-autonomous dendritic cell migration in confined environments. , 2011, Blood.

[92]  R. Locksley,et al.  Spatiotemporally separated antigen uptake by alveolar dendritic cells and airway presentation to T cells in the lung , 2012, The Journal of experimental medicine.

[93]  A. Prescott,et al.  TLR ligand–induced podosome disassembly in dendritic cells is ADAM17 dependent , 2008, The Journal of cell biology.

[94]  W. Wood,et al.  SCAR/WAVE-mediated processing of engulfed apoptotic corpses is essential for effective macrophage migration in Drosophila , 2013, Cell Death and Differentiation.

[95]  W. Agace,et al.  The diverse ontogeny and function of murine small intestinal dendritic cell/macrophage subsets. , 2010, Immunobiology.

[96]  D. Ganea,et al.  IFN-β Inhibits Dendritic Cell Migration through STAT-1–Mediated Transcriptional Suppression of CCR7 and Matrix Metalloproteinase 9 , 2010, The Journal of Immunology.

[97]  T. Bretschneider,et al.  The Diaphanous-related formin dDia2 is required for the formation and maintenance of filopodia , 2005, Nature Cell Biology.

[98]  F. Ginhoux,et al.  Origin of the lamina propria dendritic cell network. , 2009, Immunity.

[99]  Micah Dembo,et al.  Traction force microscopy in Dictyostelium reveals distinct roles for myosin II motor and actin-crosslinking activity in polarized cell movement , 2007, Journal of Cell Science.

[100]  M. Tessier-Lavigne,et al.  Semaphorins guide the entry of dendritic cells into the lymphatics by activating myosin II , 2010, Nature Immunology.

[101]  S. Narumiya,et al.  Rho-mDia1 pathway is required for adhesion, migration, and T-cell stimulation in dendritic cells. , 2010, Blood.

[102]  L. Ng,et al.  Migratory Dermal Dendritic Cells Act as Rapid Sensors of Protozoan Parasites , 2008, PLoS pathogens.

[103]  M. Yáñez-Mó,et al.  Myosin IIA is involved in the endocytosis of CXCR4 induced by SDF-1α , 2007, Journal of Cell Science.

[104]  C. Marshall,et al.  The plasticity of cytoskeletal dynamics underlying neoplastic cell migration. , 2010, Current opinion in cell biology.

[105]  G. Charras,et al.  Polar stimulation and constrained cell migration in microfluidic channels. , 2007, Lab on a chip.

[106]  J. Aubertin,et al.  Fine control of nuclear confinement identifies a threshold deformation leading to lamina rupture and induction of specific genes. , 2012, Integrative biology : quantitative biosciences from nano to macro.

[107]  Mehmet Toner,et al.  Spontaneous migration of cancer cells under conditions of mechanical confinement. , 2009, Integrative biology : quantitative biosciences from nano to macro.

[108]  K. Katagiri,et al.  Crucial functions of the Rap1 effector molecule RAPL in lymphocyte and dendritic cell trafficking , 2004, Nature Immunology.

[109]  M. Dembo,et al.  Modulation of Cell Adhesion and Motility in the Immune System by Myo1f , 2006, Science.

[110]  C J Murphy,et al.  Effects of synthetic micro- and nano-structured surfaces on cell behavior. , 1999, Biomaterials.