Dendritic Cell Podosome Dynamics Does Not Depend on the F-actin Regulator SWAP-70

Anne Götz,Rolf Jessberger

doi:10.1371/journal.pone.0060642

Anne Götz, Rolf Jessberger

Open Access

https://doi.org/10.1371/journal.pone.0060642

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Abstract

In addition to classical adhesion structures like filopodia or focal adhesions, dendritic cells similar to macrophages and osteoclasts assemble highly dynamic F-actin structures called podosomes. They are involved in cellular processes such as extracellular matrix degradation, bone resorption by osteoclasts, and trans-cellular diapedesis of lymphocytes. Besides adhesion and migration, podosomes enable dendritic cells to degrade connective tissue by matrix metalloproteinases. SWAP-70 interacts with RhoGTPases and F-actin and regulates migration of dendritic cells. SWAP-70 deficient osteoclasts are impaired in F-actin-ring formation and bone resorption. In the present study, we demonstrate that SWAP-70 is not required for podosome formation and F-actin turnover in dendritic cells. Furthermore, we found that toll-like receptor 4 ligand induced podosome disassembly and podosome-mediated matrix degradation is not affected by SWAP-70 in dendritic cells. Thus, podosome formation and function in dendritic cells is independent of SWAP-70.

Highlights

Dendritic cells (DCs) are the most efficient antigen presenting cells and act as key regulators of the immune system [1]
Together with its role in regulation of the F-actin cytoskeleton these findings suggested a role of SWAP-70 in DC podosome formation and dynamics, which we set out to test in this study
We have demonstrated very recently that SWAP-70 deficient osteoclasts are impaired in formation of distinct podosome structures and bone resorption capacity [20], known to require RhoA activity for their formation [19]

Summary

Introduction

Dendritic cells (DCs) are the most efficient antigen presenting cells and act as key regulators of the immune system [1]. DCs undergo a tightly regulated maturation process that enables them to migrate to secondary lymphoid organs to initiate immune responses. This maturation process is typically accompanied by changes in DC morphology and behavior. Activated DCs up-regulate co-stimulatory molecules to induce either immunity or tolerance by presenting acquired antigens to naıve T cells in lymph nodes [1,2]. Elucidating the mechanisms that regulate DC migration from peripheral tissues to lymph nodes upon activation is essential to understand central functions of the immune system

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