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.

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 Topological Small-World Organization of the Fibroblastic Reticular Cell Network Determines Lymph Node Functionality

PLoS Biology ◽  
2016 ◽  
Vol 14 (7) ◽  
pp. e1002515 ◽  
Author(s):  
Mario Novkovic ◽  
Lucas Onder ◽  
Jovana Cupovic ◽  
Jun Abe ◽  
David Bomze ◽  
...  
Keyword(s):  
Lymph Node ◽  
Small World ◽  
Reticular Cell ◽  
Cell Network ◽  
Fibroblastic Reticular Cell ◽  
World Organization

scholarly journals Development of follicular dendritic cells in lymph nodes depends on retinoic acid mediated signaling

2020 ◽  
Author(s):  
Jasper J. Koning ◽  
Anusha Rajaraman ◽  
Rogier M. Reijmers ◽  
Tanja Konijn ◽  
Junliang Pan ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Lymph Nodes ◽  
Retinoic Acid Receptor ◽  
Follicular Dendritic Cell ◽  
Reticular Cell ◽  
Lineage Differentiation ◽  
Common Precursor ◽  
Fibroblastic Reticular Cell ◽  
Selective Generation ◽  
Follicular Dendritic

AbstractSpecialized stromal cells occupy and help define B- and T cell domains, which is crucial for proper functioning of our immune system. Signaling through lymphotoxin and TNF-receptors is crucial for development of different stromal subsets which are thought to arise from a common precursor. However, mechanisms that control the selective generation of the different stromal phenotypes are not known.Here we show that in mice, retinoic acid mediated signaling is important for the differentiation of precursors towards the Cxcl13pos follicular dendritic cell (FDC) lineage, while blocking lymphotoxin mediated Ccl19pos fibroblastic reticular cell (FRC) lineage differentiation. Consequently, we see at day of birth Cxcl13posCcl19neg/low and Cxcl13neg/lowCcl19pos cells within neonatal lymph nodes.Furthermore, ablation of retinoic acid receptor signaling in stromal precursors early after birth reduces Cxcl13 expression, while in addition, complete blockade of retinoic acid signaling prevents formation of FDC networks in lymph nodes.

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