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Data-driven modelling of the FRC network for studying the fluid flow in the conduit system

Rostislav Savinkov, Alexey Kislitsyn, Daniel J. Watson, Raoul van Loon, Igor Sazonov, Mario Novkovic, Lucas Onder, Gennady Bocharov
2017 Engineering applications of artificial intelligence  
The FRC network model is then used to analyze the fluid flow through the network. A first observation is that the pressure gradient is approximately linear, which suggests homogeneity of the network.  ...  We present a computational method to model the geometry of the FRC network.  ...  The generated FRC network is finally used to study the fluid flow through lymph node conduits in Section 4.  ... 
doi:10.1016/j.engappai.2016.10.007 fatcat:idg7yhpkvzadhel6t35ircsva4

Communication, construction, and fluid control: lymphoid organ fibroblastic reticular cell and conduit networks

Sophie E. Acton, Lucas Onder, Mario Novkovic, Victor G. Martinez, Burkhard Ludewig
2021 Trends in immunology  
Moreover, FRCs produce and ensheath a network of extracellular matrix (ECM) microfibers called the conduit system.  ...  We discuss the intricate relationships between the cellular FRC and the fibrillar conduit networks, which together form the basis for efficient communication between immune cells and the tissues they survey  ...  Acknowledgments This study received financial support from the Swiss National Science Foundation (grants 177208 and 166500 to B.L.), a European Research Council starting grant (LNEXPANDS to S.E.A.), a  ... 
doi:10.1016/j.it.2021.07.003 pmid:34362676 fatcat:lnjkhh5qhfantnwgomvoigxn6i

Integrative Computational Modeling of the Lymph Node Stromal Cell Landscape

Mario Novkovic, Lucas Onder, Hung-Wei Cheng, Gennady Bocharov, Burkhard Ludewig
2018 Frontiers in Immunology  
Lastly, we discuss briefly the importance of hybrid and multi-scale modeling approaches in immunology and the technical challenges involved.  ...  We explore various mathematical studies of intranodal T cell motility and migration, their interactions with the LN-resident stromal cells, and computational models of functional chemokine gradient fields  ...  Data-driven modeling of the FRC network for studying the fluid 91. Barabasi AL, Oltvai ZN. Network biology: understanding the cell’s functional flow in the conduit system.  ... 
doi:10.3389/fimmu.2018.02428 pmid:30405623 pmcid:PMC6206207 fatcat:jhfxoeoenbbnjkiiwnjaesu7cu

The microanatomy of T-cell responses

Tim Lämmermann, Michael Sixt
2008 Immunological Reviews  
The success rate of such interactions is extremely low, because the precursor frequency of a naive T cell recognizing a specific antigen is in the range of 1:10 5 -10 6 .  ...  We describe the association between fibroblastic reticular cell, conduit, DC, and T cell as the essential functional unit of the T-cell cortex.  ...  Consequently, all blood vessels in the LN are shielded from the permeable sinus and are embedded into the filtrating conduit system of the FRC network.  ... 
doi:10.1111/j.1600-065x.2008.00592.x pmid:18275473 fatcat:ekmhnmjr7fc7zlxl5mmwyqifti

Tumor-induced stromal reprogramming drives lymph node transformation

Angela Riedel, David Shorthouse, Lisa Haas, Benjamin A Hall, Jacqueline Shields
2016 Nature Immunology  
Here we show that FRCs specifically of TDLNs proliferate in response to tumor-derived cues and that the network they form is remodeled.  ...  Principal component analysis Principal Component Analysis (PCA) was performed using the R "stats" package. Log2 transformed data was used as input for the analysis.  ...  We wish to thank the CIMR flow cytometry core facility for advice and support in flow cytometry and cell sorting applications. Work  ... 
doi:10.1038/ni.3492 pmid:27400148 pmcid:PMC4994871 fatcat:3je7bd3pmbchpa45iqvojf434u

The Biophysics of Lymphatic Transport: Engineering Tools and Immunological Consequences

Meghan J. O'Melia, Amanda W. Lund, Susan N. Thomas
2019 iScience  
Finally, we discuss the current understanding for how changes in lymphatic transport and lymph node biomechanics contribute to pathogenesis of conditions including cancer, aging, neurodegeneration, and  ...  Here we review the functional role of lymphatic transport and lymph node biomechanics in immunity.  ...  flow of filtered lymph through the conduit system.  ... 
doi:10.1016/j.isci.2019.11.005 pmid:31739172 pmcid:PMC6864335 fatcat:tjy6sjl2wvdbrcwi4elesjm5uu

Mechanical Forces during Lymph Node Expansion Govern Fibroblastic Reticular Network Remodeling [article]

Harry L Horsnell, Robert J Tetley, Henry de Belly, Spiros Makris, Agnesska C Benjamin, Ewa Paluch, Yanlan Mao, Sophie E Acton
2021 bioRxiv   pre-print
Together this study demonstrates mechanical forces are generated and sensed through the FRC network to determine lymph node expansion required for an adaptive immune response.  ...  We found that FRC network tension is a critical cue in controlling lymph node expansion gating the initiation of FRC proliferation.  ...  We thank Ki Hng, Andrew Vaughan, and the core staff at MRC-LMCB for light microscopy expertise and Dr Yanping Guo at the UCL Cancer institute flow cytometry facility for assistance in the work contained  ... 
doi:10.1101/2021.05.27.446027 fatcat:mnjrtuuwwzezxh5uwpyczmp7em

Exploring the role of stromal osmoregulation in cancer and disease using executable modelling

David Shorthouse, Angela Riedel, Emma Kerr, Luisa Pedro, Dóra Bihary, Shamith Samarajiwa, Carla P. Martins, Jacqueline Shields, Benjamin A. Hall
2018 Nature Communications  
We present an executable model of osmotic regulation and membrane transport in mammalian cells, providing a mechanistic explanation for phenotype change in varied disease states, and accurately predicting  ...  Furthermore, we predict and verify a synergistic drug combination in vitro, of sodium and chloride channel inhibitors, which target the osmoregulatory network to reduce cancer-associated phenotypes in  ...  Acknowledgements We thank the Hall and Shields groups, Alex Gaunt, Stephen Woodhouse, and Phil Jones for useful discussions.  ... 
doi:10.1038/s41467-018-05414-y pmid:30069015 pmcid:PMC6070494 fatcat:eruqr77hhnazdodusn74y2426a

Expansion of Cortical and Medullary Sinuses Restrains Lymph Node Hypertrophy during Prolonged Inflammation

K. W. Tan, K. P. Yeo, F. H. S. Wong, H. Y. Lim, K. L. Khoo, J.-P. Abastado, V. Angeli
2012 Journal of Immunology  
We are grateful to Laurent Renia (Singapore Immunology Network) for the gift of the anti-CD62L Ab and Bronislaw Pytowski (ImClone Systems) for the gift of anti-VEGFR3 and VEGFR2 Abs.  ...  (Flow Cytometry Lab, National University of Singapore) for sharing expertise.  ...  Because other groups described that interstitial flow can modulate FRC organization and function (43) and, in our model, extranodal VEGF-A may be transported within the FRC conduit system and subsequently  ... 
doi:10.4049/jimmunol.1101854 pmid:22430738 fatcat:oc43qkwqpfgb3k6kehreobyoyu

Stromal cell contributions to the homeostasis and functionality of the immune system

Scott N. Mueller, Ronald N. Germain
2009 Nature reviews. Immunology  
A defining characteristic of the immune system is the constant movement of many of its constituent cells through the secondary lymphoid tissues, mainly the spleen and lymph nodes, where crucial interactions  ...  What has only recently been recognized is the role that nonhaematopoietic stromal elements have in multiple aspects of immune cell migration, activation and survival.  ...  Acknowledgments The authors would like to thank I. Ifrim for invaluable assistance with immunohistochemistry to generate the images in the figures, A. O. Anderson, J. Egen, and W.  ... 
doi:10.1038/nri2588 pmid:19644499 pmcid:PMC2785037 fatcat:v3u6yjjhwjcmtg6i3xpnhol2ye

Lymph node conduits transport virions for rapid T cell activation

Glennys V. Reynoso, Andrea S. Weisberg, John P. Shannon, Daniel T. McManus, Lucas Shores, Jeffrey L. Americo, Radu V. Stan, Jonathan W. Yewdell, Heather D. Hickman
2019 Nature Immunology  
These results reveal that it is possible for even large virions to flow through LN conduits and infect dendritic cells within the T cell zone to prime CD8+ T cells.  ...  Notably, many rapidly infected cells in the LN interior were adjacent to LN conduits. Through the use of confocal and electron microscopy, we clearly visualized virions within conduits.  ...  Pierson (Viral Pathogenesis Section, Laboratory of Viral Diseases, NIAID) for assistance with ZIKV infection and J.  ... 
doi:10.1038/s41590-019-0342-0 pmid:30886418 pmcid:PMC6474694 fatcat:bx2brmac6jbg5kwbng2fyonkny

Immune function and dysfunction are determined by lymphoid tissue efficacy

Spyridon Makris, Charlotte M. de Winde, Harry L. Horsnell, Jesús A. Cantoral-Rebordinos, Rachel E. Finlay, Sophie E. Acton
2022 Disease Models & Mechanisms  
Understanding the role of lymphoid tissues in immune responses to a wide range of pathologies allows us to take a fuller systemic view of disease progression.  ...  We discuss the functional role of lymphoid tissue in disease progression and explore the changes to lymphoid tissue structure and function driven by infection, chronic inflammatory conditions and cancer  ...  Viruses have evolved mechanisms to utilise the FRC network to evade the immune system.  ... 
doi:10.1242/dmm.049256 pmid:35072206 pmcid:PMC8807573 fatcat:opi5is3wmnfxvfdyp43wmccqma

A novel bacterial artificial chromosome-transgenic Podoplanin–Cre mouse targets lymphoid organ stromal cells in vivo

Lucas Onder
2011 Frontiers in Immunology  
This study received financial support from the Swiss National Science Foundation (CRSII3_125447 and 130823/1 to Burkhard Ludewig) and from the Austrian Genome Research Programme GEN-AU II and III (Austromouse  ...  ACKNOWLEDGMENTS We would like to thank Rita de Giuli and Eva Allgäuer for technical support.  ...  Furthermore, FRCs form the microvascular conduit system that distributes small lymph-borne antigens within the lymphoid tissue (Sixt et al., 2005) .  ... 
doi:10.3389/fimmu.2011.00050 pmid:22566840 pmcid:PMC3342134 fatcat:e4vzjcvdazbrreikx4fwja3boa

Development and Immunological Function of Lymph Node Stromal Cells

Natalia Barbara Pikor, Hung-Wei Cheng, Lucas Onder, Burkhard Ludewig
2021 Journal of Immunology  
In this review, we go over recent advances in genetic models and high-resolution transcriptomic analyses that have propelled the finer resolution of the stromal cell infrastructure of lymph nodes, revealing  ...  Moreover, we discuss how changes in the activation state of poised stromal cell-underpinned niches rather than on-demand differentiation of new stromal cell subsets govern the efficient interaction of  ...  Moreover, the physical stretching of the FRC network during inflammation may promote temporary conduit permeability (60, 61) , which in turn has been shown to promote the passive entry of IgM into conduits  ... 
doi:10.4049/jimmunol.2000914 pmid:33397739 fatcat:bcvxkopzhnd7fafbyieppnt4mm

Lymph node stromal cell subsets – emerging specialists for tailored tissue-specific immune responses

Mangge Zou, Carolin Wiechers, Jochen Huehn
2021 International Journal of Medical Microbiology  
for the modulation of adaptive immune responses.  ...  In this review, we summarize current advances on the pivotal roles that LNSCs play in orchestrating adaptive immune responses during homeostasis and infection, and highlight the imprinting of location-specific  ...  Acknowledgements This work was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) in the framework of the priority program SPP1656 "Intestinal microbiotaa microbial ecosystem  ... 
doi:10.1016/j.ijmm.2021.151492 pmid:33676241 fatcat:ejmxk65735dkxgyzb4b3v42kim
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