Université PSL

Publications

RECHERCHER

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Role of calcium permeable channels in dendritic cell migration.
Sáez PJ, Sáez JC, Lennon-Duménil AM, Vargas P.
Curr Opin Immunol. - 52 74-80 - doi: 10.1016/j.coi.2018.04 - 2018
Calcium ion (Ca2+) is an essential second messenger involved in multiple cellular and subcellular processes. Ca2+ can be released and sensed globally or locally within cells, providing complex signals of variable amplitudes and time-scales. The key function of Ca2+ in the regulation of acto-myosin contractility has provided a simple explanation for its role in the regulation of immune cell migration. However, many questions remain, including the identity of the Ca2+ stores, channels and upstream signals involved in this process. Here, we focus on dendritic cells (DCs), because their immune sentinel function heavily relies on their capacity to migrate within tissues and later on between tissues and lymphoid organs. Deciphering the mechanisms by which cytoplasmic Ca2+ regulate DC migration should shed light on their role in initiating and tuning immune responses.
Mixed Copolymer Adlayers Allowing Reversible Thermal Control of Single Cell Aspect Ratio.
Dalier F, Dubacheva GV, Coniel M, Zanchi D, Galtayries A, Piel M, Marie E, Tribet C.
ACS Appl Mater Interfaces - 10(3) 2253-2258 - doi: 10.1021/acsami.7b18513. - 2018
Dynamic guidance of living cells is achieved by fine-tuning and spatiotemporal modulation on artificial polymer layers enabling reversible peptide display. Adjustment of surface composition and interactions is obtained by coadsorption of mixed poly(lysine) derivatives, grafted with either repellent PEG, RGD adhesion peptides, or T-responsive poly(N-isopropylacrylamide) strands. Deposition of mixed adlayers provides a straightforward mean to optimize complex substrates, which is here implemented to achieve (1) thermal control of ligand accessibility and (2) adjustment of relative adhesiveness between adjacent micropatterns, while preserving cell attachment during thermal cycles. The reversible polarization of HeLa cells along orthogonal stripes mimics guidance along natural matrices.
Retraction Notice to: FMN2 Makes Perinuclear Actin to Protect Nuclei during Confined Migration and Promote Metastasis.
Skau CT, Fischer RS, Gurel P, Thiam HR, Tubbs A, Baird MA, Davidson MW, Piel M, Alushin GM, Nussenzweig A, Steeg PS, Waterman CM.
Cell - 173(2) 529 - doi: 10.1016/j.cell.2018.03.058 - 2018
FMN2 Makes Perinuclear Actin to Protect Nuclei during Confined Migration and Promote Metastasis. [Cell. 2016]
Leukocyte Migration and Deformation in Collagen Gels and Microfabricated Constrictions
Sáez PJ, Barbier L, Attia R, Thiam HR, Piel M, Vargas P.
Methods Mol Biol. - 1749 361-373 - doi: 10.1007/978-1-4939-7701-7_26. - 2018
In multicellular organisms, cell migration is a complex process. Examples of this are observed during cell motility in the interstitial space, full of extracellular matrix fibers, or when cells pass through endothelial layers to colonize or exit specific tissues. A common parameter for both situations is the fast adaptation of the cellular shape to their irregular landscape. In this chapter, we describe two methods to study cell migration in complex environments. The first one consists in a multichamber device for the visualization of cell haptotaxis toward the collagen-binding chemokine CCL21. This method is used to study cell migration as well as deformations during directed motility, as in the interstitial space. The second one consists in microfabricated channels connected to small constrictions. This procedure allows the study of cell deformations when single cells migrate through small holes and it is analogous to passage of cells through endothelial layers, resulting in a simplified system to study the mechanisms operating during transvasation. Both methods combined provide a powerful hub for the study of cell plasticity during migration in complex environments.
Leukocyte Migration and Deformation in Collagen Gels and Microfabricated Constrictions.
Sáez PJ, Barbier L, Attia R, Thiam HR, Piel M, Vargas P
Methods Mol Biol. - 1749 361-373 - doi: 10.1007/978-1-4939-7701-7_26 - 2018
In multicellular organisms, cell migration is a complex process. Examples of this are observed during cell motility in the interstitial space, full of extracellular matrix fibers, or when cells pass through endothelial layers to colonize or exit specific tissues. A common parameter for both situations is the fast adaptation of the cellular shape to their irregular landscape. In this chapter, we describe two methods to study cell migration in complex environments. The first one consists in a multichamber device for the visualization of cell haptotaxis toward the collagen-binding chemokine CCL21. This method is used to study cell migration as well as deformations during directed motility, as in the interstitial space. The second one consists in microfabricated channels connected to small constrictions. This procedure allows the study of cell deformations when single cells migrate through small holes and it is analogous to passage of cells through endothelial layers, resulting in a simplified system to study the mechanisms operating during transvasation. Both methods combined provide a powerful hub for the study of cell plasticity during migration in complex environments.
Mixed Copolymer Adlayers Allowing Reversible Thermal Control of Single Cell Aspect Ratio.
Dalier F1, Dubacheva GV1, Coniel M1, Zanchi D1,2, Galtayries A, Piel M, Marie E1, Tribet C1.
ACS Appl Mater Interfaces - 10(3) 2253-2258 - doi: 10.1021/acsami.7b18513. - 2018
Dynamic guidance of living cells is achieved by fine-tuning and spatiotemporal modulation on artificial polymer layers enabling reversible peptide display. Adjustment of surface composition and interactions is obtained by coadsorption of mixed poly(lysine) derivatives, grafted with either repellent PEG, RGD adhesion peptides, or T-responsive poly(N-isopropylacrylamide) strands. Deposition of mixed adlayers provides a straightforward mean to optimize complex substrates, which is here implemented to achieve (1) thermal control of ligand accessibility and (2) adjustment of relative adhesiveness between adjacent micropatterns, while preserving cell attachment during thermal cycles. The reversible polarization of HeLa cells along orthogonal stripes mimics guidance along natural matrices.
Diversification of human plasmacytoid predendritic cells in response to a single stimulus
Alculumbre SG, Saint-André V, Di Domizio J, Vargas P, Sirven P, Bost P, Maurin M, Maiuri P, Wery M, Roman MS, Savey L, Touzot M, Terrier B, Saadoun D, Conrad C, Gilliet M, Morillon A, Soumelis V
Nat Immunol. - 19(1) 63-75 - doi: 10.1038/s41590-017-0012-z. - 2018
Innate immune cells adjust to microbial and inflammatory stimuli through a process termed environmental plasticity, which links a given individual stimulus to a unique activated state. Here, we report that activation of human plasmacytoid predendritic cells (pDCs) with a single microbial or cytokine stimulus triggers cell diversification into three stable subpopulations (P1-P3). P1-pDCs (PD-L1+CD80-) displayed a plasmacytoid morphology and specialization for type I interferon production. P3-pDCs (PD-L1-CD80+) adopted a dendritic morphology and adaptive immune functions. P2-pDCs (PD-L1+CD80+) displayed both innate and adaptive functions. Each subpopulation expressed a specific coding- and long-noncoding-RNA signature and was stable after secondary stimulation. P1-pDCs were detected in samples from patients with lupus or psoriasis. pDC diversification was independent of cell divisions or preexisting heterogeneity within steady-state pDCs but was controlled by a TNF autocrine and/or paracrine communication loop. Our findings reveal a novel mechanism for diversity and division of labor in innate immune cells.
Flow and fracture near the sol–gel transition of silica nanoparticle suspensions
Gustavo E. Gimenes a and Elisabeth Bouchaudbc
Soft Matter - 14 8036-8043 - DOI:10.1039/C8SM01247D - 2018
We analyze the evolution of the mechanical response of a colloidal suspension to an external tensile stress, from fracture to flow, as a function of the distance from the sol–gel transition. We cease to observe cracks at a finite distance from the transition. In an intermediate region where the phenomenon is clearly hysteretic, we observe the coexistence of both flow and fracture. Even when cracks are observed, the material in fact flows over a distance that increases in the vicinity of the transition.
Caveolin-1 Expression Increases upon Maturation in Dendritic Cells and Promotes Their Migration to Lymph Nodes Thereby Favoring the Induction of CD8 T Cell Responses.
Oyarce C, Cruz-Gomez S, Galvez-Cancino F, Vargas P, Moreau HD, Diaz-Valdivia N, Diaz J, Salazar-Onfray FA, Pacheco R6, Lennon-Dumenil AM, Quest AFG, Lladser A.
Front Immunol - 13;8 1794 - doi: 10.3389/fimmu.2017.01794 - 2017
Dendritic cell (DC) trafficking from peripheral tissues to lymph nodes (LNs) is a key step required to initiate T cell responses against pathogens as well as tumors. In this context, cellular membrane protrusions and the actin cytoskeleton are essential to guide DC migration towards chemotactic signals. Caveolin-1 (CAV1) is a scaffolding protein that modulates signaling pathways leading to remodeling of the actin cytoskeleton and enhanced migration of cancer cells. However, whether CAV1 is relevant for DC function and specifically for DC migration to LNs is unknown. Here, we show that CAV1 expression is upregulated in DCs upon LPS- and TNF-α-induced maturation. CAV1 deficiency did not affect differentiation, maturation, or the ability of DCs to activate CD8+ T cells in vitro. However, CAV1-deficient (CAV1-/-) DCs displayed reduced in vivo trafficking to draining LNs in control and inflammatory conditions. In vitro, CAV1-/- DCs showed reduced directional migration in CCL21 gradients in transwell assays without affecting migration velocity in confined microchannels or three-dimensional collagen matrices. In addition, CAV1-/- DCs displayed reduced activation of the small GTPase Rac1, a regulator of actin cytoskeletal remodeling, and lower numbers of F-actin-forming protrusions. Furthermore, mice adoptively transferred with peptide-pulsed CAV1-/- DCs showed reduced CD8+ T cell responses and antitumor protection. Our results suggest that CAV1 promotes the activation of Rac1 and the formation of membrane protrusions that favor DC chemotactic trafficking toward LNs where they can initiate cytotoxic T cell responses.
Forcing Entry into the Nucleus.
AlexisLomakin, GuilhermeNader, MatthieuPiel
Cell - 43 547-548 - https://doi.org/10.1016/j.devcel.2017.11.015 - 2017
Nuclear pore complexes tightly regulate nucleo-cytoplasmic transport, controlling the nuclear concentration of several transcription factors. In a recent issue of Cell, Elosegui-Artola et al. (2017) show that nuclear deformation modulates the nuclear entry rates of YAP/TAZ via nuclear pore stretching, clarifying how forces affect gene transcription.

325 publications.