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

Cesar Oyarce, Sebastián Cruz-Gomez, Felipe Galvez-Cancino, Pablo Vargas, Hélène D. Moreau, Natalia Diaz-Valdivia, Jorge Diaz, Flavio Andres Salazar-Onfray, Rodrigo Pacheco, Ana Maria Lennon-Dumenil, Andrew F.G. Quest, Alvaro Lladser

Resultado de la investigación: Article

5 Citas (Scopus)

Resumen

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-a-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.

Idioma originalEnglish
Número de artículo1794
PublicaciónFrontiers in Immunology
Volumen8
N.ºDEC
DOI
EstadoPublished - 13 dic 2017

Huella dactilar

Caveolin 1
Dendritic Cells
Lymph Nodes
T-Lymphocytes
Cell Movement
Actin Cytoskeleton
Actins
Cell Surface Extensions
Membranes
Monomeric GTP-Binding Proteins
Neoplasms
Collagen
Peptides

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Citar esto

Oyarce, Cesar ; Cruz-Gomez, Sebastián ; Galvez-Cancino, Felipe ; Vargas, Pablo ; Moreau, Hélène D. ; Diaz-Valdivia, Natalia ; Diaz, Jorge ; Salazar-Onfray, Flavio Andres ; Pacheco, Rodrigo ; Lennon-Dumenil, Ana Maria ; Quest, Andrew F.G. ; Lladser, Alvaro. / 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. En: Frontiers in Immunology. 2017 ; Vol. 8, N.º DEC.
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title = "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",
abstract = "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-a-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.",
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author = "Cesar Oyarce and Sebasti{\'a}n Cruz-Gomez and Felipe Galvez-Cancino and Pablo Vargas and Moreau, {H{\'e}l{\`e}ne D.} and Natalia Diaz-Valdivia and Jorge Diaz and Salazar-Onfray, {Flavio Andres} and Rodrigo Pacheco and Lennon-Dumenil, {Ana Maria} and Quest, {Andrew F.G.} and Alvaro Lladser",
year = "2017",
month = "12",
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doi = "10.3389/fimmu.2017.01794",
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Oyarce, C, Cruz-Gomez, S, Galvez-Cancino, F, Vargas, P, Moreau, HD, Diaz-Valdivia, N, Diaz, J, Salazar-Onfray, FA, Pacheco, R, Lennon-Dumenil, AM, Quest, AFG & Lladser, A 2017, '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', Frontiers in Immunology, vol. 8, n.º DEC, 1794. https://doi.org/10.3389/fimmu.2017.01794

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, Cesar; Cruz-Gomez, Sebastián; Galvez-Cancino, Felipe; Vargas, Pablo; Moreau, Hélène D.; Diaz-Valdivia, Natalia; Diaz, Jorge; Salazar-Onfray, Flavio Andres; Pacheco, Rodrigo; Lennon-Dumenil, Ana Maria; Quest, Andrew F.G.; Lladser, Alvaro.

En: Frontiers in Immunology, Vol. 8, N.º DEC, 1794, 13.12.2017.

Resultado de la investigación: Article

TY - JOUR

T1 - 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

AU - Oyarce, Cesar

AU - Cruz-Gomez, Sebastián

AU - Galvez-Cancino, Felipe

AU - Vargas, Pablo

AU - Moreau, Hélène D.

AU - Diaz-Valdivia, Natalia

AU - Diaz, Jorge

AU - Salazar-Onfray, Flavio Andres

AU - Pacheco, Rodrigo

AU - Lennon-Dumenil, Ana Maria

AU - Quest, Andrew F.G.

AU - Lladser, Alvaro

PY - 2017/12/13

Y1 - 2017/12/13

N2 - 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-a-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.

AB - 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-a-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.

KW - Antitumor immune response

KW - Caveolin-1

KW - CD8 T cell activation

KW - Chemotaxis

KW - Dendritic cells

KW - Migration

UR - http://www.scopus.com/inward/record.url?scp=85037976546&partnerID=8YFLogxK

U2 - 10.3389/fimmu.2017.01794

DO - 10.3389/fimmu.2017.01794

M3 - Article

AN - SCOPUS:85037976546

VL - 8

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

IS - DEC

M1 - 1794

ER -