scholarly journals Fibroblastic reticular cell response to dendritic cells requires coordinated activity of podoplanin, CD44 and CD9

2021 ◽  
Author(s):  
Charlotte M de Winde ◽  
Spyridon Makris ◽  
Lindsey Millward ◽  
Jesús Cantoral Rebordinos ◽  
Agnesska C Benjamin ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Lymph Node ◽  
Molecular Mechanisms ◽  
Reticular Cell ◽  
Step Process ◽  
Actomyosin Contractility ◽  
Fibroblastic Reticular Cell ◽  
Reticular Cells ◽  
Partner Proteins

In adaptive immunity, CLEC-2+ dendritic cells (DCs) contact fibroblastic reticular cells (FRCs) inhibiting podoplanin-dependent actomyosin contractility, permitting FRC spreading and lymph node (LN) expansion. The molecular mechanisms controlling LN remodelling are incompletely understood. We asked how podoplanin is regulated on FRCs in the early phase of LN expansion, and which other proteins are required for the FRC response to DCs. We find that podoplanin and its partner proteins CD44 and CD9 are differentially expressed by specific LN stromal populations in vivo, and their expression in FRCs is coregulated by CLEC-2. Both CD44 and CD9 suppress podoplanin-dependent contractility. We find that beyond contractility, podoplanin is required for FRC polarity and alignment. Independently of podoplanin, CD44 and CD9 affect FRC-FRC interactions. Further, our data show that remodelling of the FRC cytoskeleton in response to DCs is a two-step process requiring podoplanin partner proteins CD44 and CD9. Firstly, CLEC-2/podoplanin-binding inhibits FRC contractility, and secondly FRCs form protrusions and spread which requires both CD44 and CD9. Together, we show a multi-faceted FRC response to DCs, which requires CD44 and CD9 in addition to podoplanin.

scholarly journals Fibroblastic Reticular Cell Response to Dendritic Cells Requires Coordinated Activity of Podoplanin, CD44 and CD9

2019 ◽  
Author(s):  
Charlotte M. de Winde ◽  
Spyridon Makris ◽  
Lindsey Millward ◽  
Jesús Cantoral Rebordinos ◽  
Agnesska C. Benjamin ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Lymph Node ◽  
Molecular Mechanisms ◽  
Cell Contact ◽  
Reticular Cell ◽  
Actomyosin Contractility ◽  
Fibroblastic Reticular Cell ◽  
Reticular Cells ◽  
Partner Proteins

Lymph node expansion is pivotal for adaptive immunity. CLEC-2+ migratory dendritic cells (DCs) interact with fibroblastic reticular cells (FRCs) to inhibit podoplanin-dependent actomyosin contractility, permitting FRC spreading and lymph node expansion. However, the molecular mechanisms controlling lymph node remodelling are not fully understood. We asked how podoplanin is regulated on FRCs in the early phase of lymph node expansion in vivo, and further, which other FRC markers are required for FRCs to respond to CLEC-2+ DCs. We find that expression of podoplanin and its partner proteins CD44 and CD9 in FRCs is coregulated by CLEC-2, and is differentially expressed by specific lymph node stromal populations in vivo. We find that beyond contractility, podoplanin is required for polarity and alignment of FRCs. Both CD44 and CD9 act to dampen podoplanin-dependent contractility, and colocalize with podoplanin in different areas of the cell membrane. Independently of podoplanin, CD44 and CD9 affect the degree of cell-cell contact and overlap between neighbouring FRCs. Further, we show that both CD44 and CD9 are required for FRCs to spread and form protrusions in response to DCs. Our data show that remodelling of the FRC cytoskeleton is a two-step process requiring podoplanin partner proteins CD44 and CD9. Firstly, CLEC-2/podoplanin-binding drives relaxation of actomyosin contractility, and secondly FRCs form protrusions and spread which requires both CD44 and CD9. Together, we show a multi-faceted response of FRCs to DCs, which requires CD44 and CD9 in addition to podoplanin.

scholarly journals Vimentin provides the mechanical resilience required for amoeboid migration and protection of the nucleus

2019 ◽  
Author(s):  
Luiza Da Cunha Stankevicins ◽  
Marta Urbanska ◽  
Daniel AD. Flormann ◽  
Emmanuel Terriac ◽  
Zahra Mostajeran ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dendritic Cells ◽  
Cell Migration ◽  
Molecular Mechanisms ◽  
Cell Cortex ◽  
Dna Double Strand Breaks ◽  
Nuclear Positioning ◽  
Mechanical Stiffness

AbstractDendritic cells use amoeboid migration through constricted passages to reach the lymph nodes, and this homing function is crucial for immune responses. Amoeboid migration requires mechanical resilience, however, the underlying molecular mechanisms for this type of migration remain unknown. Because vimentin intermediate filaments (IFs) and microfilaments regulate adhesion-dependent migration in a bidirectional manner, we analyzed if they exert a similar control on amoeboid migration. Vimentin was required for cellular resilience, via a joint interaction between vimentin IFs and F-actin. Reduced actin mobility in the cell cortex of vimentin-reduced cells indicated that vimentin promotes Factin subunit exchange and dynamics. These mechano-dynamic alterations in vimentin-deficient dendritic cells impaired amoeboid migration in confined environments in vitro and blocked lymph node homing in mouse experiments in vivo. Correct nuclear positioning is important in confined amoeboid migration both to minimize resistance and to avoid DNA damage. Vimentin-deficiency also led to DNA double strand breaks in the compressed dendritic cells, pointing to a role of vimentin in nuclear positioning. Together, these observations show that vimentin IF-microfilament interactions provide both the specific mechano-dynamics required for dendritic cell migration and the protection the genome needs in compressed spaces.Summary statementVimentin — in joint action with actin — mediates the mechanical stiffness of cells required for amoeboid cell migration through confined spaces and protects the nucleus from DNA damage.

scholarly journals Decellularized Lymph Node Scaffolding as a Carrier for Dendritic Cells to Induce Anti-Tumor Immunity

Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 553 ◽  
Author(s):  
Hung-Jun Lin ◽  
Weu Wang ◽  
Yi-You Huang ◽  
Wei-Tsen Liao ◽  
Ting-Yu Lin ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Lymph Node ◽  
Antitumor Immunity ◽  
Cpg Oligodeoxynucleotides ◽  
Mhc Ii ◽  
Decellularized Extracellular Matrix ◽  
Histocompatibility Complex ◽  
Ecm Architecture ◽  
In Vivo Delivery

In recent decades, the decellularized extracellular matrix (ECM) has shown potential as a promising scaffold for tissue regeneration. In this study, an organic acid decellularized lymph node (dLN) was developed as a carrier for dendritic cells (DCs) to induce antitumor immunity. The dLNs were prepared by formic acid, acetic acid, or citric acid treatment. The results showed highly efficient removal of cell debris from the lymph node and great preservation of ECM architecture and biomolecules. In addition, bone marrow dendritic cells (BMDCs) grown preferably inside the dLN displayed the maturation markers CD80, CD86, and major histocompatibility complex (MHC)-II, and they produced high levels of interleukin (IL)-1β, IL-6, and IL-12 cytokines when stimulated with ovalbumin (OVA) and CpG oligodeoxynucleotides (CPG-ODN). In an animal model, the BMDC-dLN completely rejected the E.G7-OVA tumor. Furthermore, the splenocytes from BMDC-dLN-immunized mice produced more interferon gamma, IL-4, IL-6, and IL-2, and they had a higher proliferation rate than other groups when re-stimulated with OVA. Hence, BMDC-dLN could be a promising DC-based scaffold for in vivo delivery to induce potent antitumor immunity.

In Vivo Imaging of Lymph Node Migration of MNP- and 111In-Labeled Dendritic Cells in a Transgenic Mouse Model of Breast Cancer (MMTV-Ras)

2011 ◽  
Vol 14 (2) ◽  
pp. 183-196 ◽  
Author(s):  
Cristina Martelli ◽  
Manuela Borelli ◽  
Luisa Ottobrini ◽  
Veronica Rainone ◽  
Anna Degrassi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dendritic Cells ◽  
Lymph Node ◽  
Mouse Model ◽  
Transgenic Mouse ◽  
In Vivo Imaging ◽  
Transgenic Mouse Model

Dendritic cell-derived IL-2 production is regulated by IL-15 in humans and in mice

Blood ◽  
2005 ◽  
Vol 105 (2) ◽  
pp. 697-702 ◽  
Author(s):  
Sonia Feau ◽  
Valeria Facchinetti ◽  
Francesca Granucci ◽  
Stefania Citterio ◽  
David Jarrossay ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Molecular Mechanisms ◽  
Interleukin 2 ◽  
Adaptive Immune ◽  
Deficient Mice ◽  
Mouse System

Abstract Dendritic cells (DCs) are involved in the initiation and regulation of innate and adaptive immune responses. Several molecular mechanisms regulate these diverse DC functions, and we have previously reported that mouse dendritic cells (mDCs) can produce interleukin-2 (IL-2) in vitro and in vivo, in response to microbial activation and T-cell-mediated stimuli. This property is shared by different DC subtypes, including Langerhans cells. Here we show that, on appropriate stimulation, human DCs, both plasmacytoid and myeloid subtypes, also express IL-2. Interestingly, the production of IL-2 by myeloid DCs is induced by T-cell-mediated stimuli and depends on the presence of IL-15. The key role of this cytokine in regulating IL-2 production was also confirmed in the mouse system. In particular, we could show that DCs from IL-15-deficient mice were strongly impaired in the ability to produce IL-2 after interactions with different microbial stimuli. Our results indicate that DC-produced IL-2 is tightly coregulated with the expression of IL-15.

scholarly journals Local Attachment Explains Small-World-Like Properties of Fibroblastic Reticular Cell Networks in Lymph Nodes

2018 ◽  
Author(s):  
Kasper M.W. Soekarjo ◽  
Johannes Textor ◽  
Rob J. de Boer
Keyword(s):  
Lymph Nodes ◽  
Preferential Attachment ◽  
Small World ◽  
Network Size ◽  
Reticular Cell ◽  
Lymphocyte Migration ◽  
Fibroblastic Reticular Cell ◽  
Reticular Cells ◽  
2D And 3D ◽  
Cell Networks

AbstractFibroblastic reticular cells (FRCs) form a cellular network that serves as the structural backbone of lymph nodes and facilitates lymphocyte migration. This FRC network has been found to have small-world properties. Using a model based on geographical preferential attachment, we simulated the formation of a variety of cellular networks and show that similar small-world properties robustly emerge under such natural conditions. By estimating the parameters of this model, we generated FRC network representations with realistic topological properties. We found that these properties change markedly when the network is expanded from a thin slice to a 3D cube. Typical small-world properties were found to persist as network size was increased. The simulated networks were very similar to 2D and 3D lattice networks. According to the used metrics, these lattice networks also have small-world properties, indicating that lattice-likeness is sufficient to become classified as a small-world network. Our results explain why FRC networks have small-world properties and provide a framework for simulating realistic FRC networks.

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