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
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-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.
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 17 January 2018.
All research outputs
#15,229,642
of 25,461,852 outputs
Outputs from Frontiers in immunology
#14,264
of 31,696 outputs
Outputs of similar age
#231,012
of 444,007 outputs
Outputs of similar age from Frontiers in immunology
#339
of 589 outputs
Altmetric has tracked 25,461,852 research outputs across all sources so far. This one is in the 38th percentile – i.e., 38% of other outputs scored the same or lower than it.
So far Altmetric has tracked 31,696 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.4. This one has gotten more attention than average, scoring higher than 52% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 444,007 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 46th percentile – i.e., 46% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 589 others from the same source and published within six weeks on either side of this one. This one is in the 40th percentile – i.e., 40% of its contemporaries scored the same or lower than it.
