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  Maturation of Monocyte-Derived DCs Leads to Increased Cellular Stiffness, Higher Membrane Fluidity, and Changed Lipid Composition

Lühr, J. J., Alex, N., Amon, L., Kräter, M., Kubánková, M., Sezgin, E., et al. (2020). Maturation of Monocyte-Derived DCs Leads to Increased Cellular Stiffness, Higher Membrane Fluidity, and Changed Lipid Composition. Frontiers in Immunology, 11: 590121. doi:10.3389/fimmu.2020.590121.

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© 2020 Lühr, Alex, Amon, Kräter, Kubánková, Sezgin, Lehmann, Heger, Heidkamp, Smith, Zaburdaev, Böckmann, Levental, Dustin, Eggeling, Guck and Dudziak. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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 Creators:
Lühr, Jennifer J.1, Author
Alex, Nils1, Author
Amon, Lukas1, Author
Kräter, Martin2, 3, Author           
Kubánková, Markéta2, 3, Author           
Sezgin, Erdinc1, Author
Lehmann, Christian H. K.1, Author
Heger, Lukas1, Author
Heidkamp, Gordon F.1, Author
Smith, Ana-Suncana1, Author
Zaburdaev, Vasily1, Author
Bockmann, Rainer A.1, Author
Levental, Ilya1, Author
Dustin, Michael L.1, Author
Eggeling, Christian1, Author
Guck, Jochen2, 3, 4, Author           
Dudziak, Diana1, Author
Affiliations:
1external, ou_persistent22              
2Guck Division, Max Planck Institute for the Science of Light, Max Planck Society, ou_3164416              
3Max-Planck-Zentrum für Physik und Medizin, Max Planck Institute for the Science of Light, Max Planck Society, ou_3164414              
4Friedrich-Alexander Universität Erlangen-Nürnberg, ou_persistent22              

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Free keywords: cell mechanics, cellular stiffness, lipids, lipidomics, monocyte-derived dendritic cells, maturation, lowdensity lipoprotein, cholesterol
 Abstract: Dendritic cells (DCs) are professional antigen-presenting cells of the immune system. Upon sensing pathogenic material in their environment, DCs start to mature, which includes cellular processes, such as antigen uptake, processing and presentation, as well as upregulation of costimulatory molecules and cytokine secretion. During maturation, DCs detach from peripheral tissues, migrate to the nearest lymph node, and find their way into the correct position in the net of the lymph node microenvironment to meet and interact with the respective T cells. We hypothesize that the maturation of DCs is well prepared and optimized leading to processes that alter various cellular characteristics from mechanics and metabolism to membrane properties. Here, we investigated the mechanical properties of monocyte-derived dendritic cells (moDCs) using real-time deformability cytometry to measure cytoskeletal changes and found that mature moDCs were stiffer compared to immature moDCs. These cellular changes likely play an important role in the processes of cell migration and T cell activation. As lipids constitute the building blocks of the plasma membrane, which, during maturation, need to adapt to the environment for migration and DC-T cell interaction, we performed an unbiased high-throughput lipidomics screening to identify the lipidome of moDCs. These analyses revealed that the overall lipid composition was significantly changed during moDC maturation, even implying an increase of storage lipids and differences of the relative abundance of membrane lipids upon maturation. Further, metadata analyses demonstrated that lipid changes were associated with the serum low-density lipoprotein (LDL) and cholesterol levels in the blood of the donors. Finally, using lipid packing imaging we found that the membrane of mature moDCs revealed a higher fluidity compared to immature moDCs. This comprehensive and quantitative characterization of maturation associated changes in moDCs sets the stage for improving their use in clinical application.

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Language(s): eng - English
 Dates: 2020-11-27
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.3389/fimmu.2020.590121
 Degree: -

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Title: Frontiers in Immunology
Source Genre: Journal
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Publ. Info: Frontiers Media SA
Pages: - Volume / Issue: 11 Sequence Number: 590121 Start / End Page: - Identifier: ISSN: 1664-3224