TY - JOUR A1 - Edlich, Alexander A1 - Volz, Pierre A1 - Brodwolf, Robert A1 - Unbehauen, Michael A1 - Mundhenk, Lars A1 - Gruber, Achim D. A1 - Hedtrich, Sarah A1 - Haag, Rainer A1 - Alexiev, Ulrike A1 - Kleuser, Burkhard T1 - Crosstalk between core-multishell nanocarriers for cutaneous drug delivery and antigen-presenting cells of the skin JF - Biomaterials : biomaterials reviews online N2 - Owing their unique chemical and physical properties core-multishell (CMS) nanocarriers are thought to underlie their exploitable biomedical use for a topical treatment of skin diseases. This highlights the need to consider not only the efficacy of CMS nanocarriers but also the potentially unpredictable and adverse consequences of their exposure thereto. As CMS nanocarriers are able to penetrate into viable layers of normal and stripped human skin ex vivo as well as in in vitro skin disease models the understanding of nanoparticle crosstalk with components of the immune system requires thorough investigation. Our studies highlight the biocompatible properties of CMS nanocarriers on Langerhans cells of the skin as they did neither induce cytotoxicity and genotoxicity nor cause reactive oxygen species (ROS) or an immunological response. Nevertheless, CMS nanocarriers were efficiently taken up by Langerhans cells via divergent endocytic pathways. Bioimaging of CMS nanocarriers by fluorescence lifetime imaging microscopy (FLIM) and flow cytometry indicated not only a localization within the lysosomes but also an energy-dependent exocytosis of unmodified CMS nanocarriers into the extracellular environment. (C) 2018 Elsevier Ltd. All rights reserved. KW - Core-multishell nanocarriers KW - Fluorescence lifetime imaging microscopy KW - Langerhans cells KW - Nanoparticle uptake KW - Nanotoxicology Y1 - 2018 U6 - https://doi.org/10.1016/j.biomaterials.2018.01.058 SN - 0142-9612 SN - 1878-5905 VL - 162 SP - 60 EP - 70 PB - Elsevier CY - Oxford ER - TY - GEN A1 - Pischon, Hannah A1 - Radbruch, Moritz A1 - Ostrowski, Anja A1 - Schumacher, Fabian A1 - Hoenzke, Stefan A1 - Kleuser, Burkhard A1 - Hedtrich, Sarah A1 - Fluhr, Joachim W. A1 - Gruber, Achim D. A1 - Mundhenk, Lars T1 - How Effective Is Tacrolimus in the Imiquimod BT - Induced Mouse Model of Psoriasis? T2 - The journal of investigative dermatology Y1 - 2017 U6 - https://doi.org/10.1016/j.jid.2017.09.019 SN - 0022-202X SN - 1523-1747 VL - 138 IS - 2 SP - 455 EP - 458 PB - Elsevier CY - New York ER - TY - JOUR A1 - Szymanski, Kolja V. A1 - Tönnies, Mario A1 - Becher, Anne A1 - Fatykhova, Diana A1 - N'Guessan, Philippe D. A1 - Gutbier, Birgitt A1 - Klauschen, Frederick A1 - Neuschäfer-Rube, Frank A1 - Schneider, Paul A1 - Rückert, Jens A1 - Neudecker, Jens A1 - Bauer, Torsten T. A1 - Dalhoff, Klaus A1 - Droemann, Daniel A1 - Gruber, Achim D. A1 - Kershaw, Olivia A1 - Temmesfeld-Wollbrueck, Bettina A1 - Suttorp, Norbert A1 - Hippenstiel, Stefan A1 - Hocke, Andreas C. T1 - Streptococcus pneumoniae-induced regulation of cyclooxygenase-2 in human lung tissue JF - The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology N2 - The majority of cases of community-acquired pneumonia are caused by Streptococcus pneumoniae and most studies on pneumococcal host interaction are based on cell culture or animal experiments. Thus, little is known about infections in human lung tissue. Cyclooxygenase-2 and its metabolites play an important regulatory role in lung inflammation. Therefore, we established a pneumococcal infection model on human lung tissue demonstrating mitogen-activated protein kinase (MAPK)-dependent induction of cyclooxygenase-2 and its related metabolites. In addition to alveolar macrophages and the vascular endothelium, cyclooxygenase-2 was upregulated in alveolar type II but not type I epithelial cells, which was confirmed in lungs of patients suffering from acute pneumonia. Moreover, we demonstrated the expression profile of all four E prostanoid receptors at the mRNA level and showed functionality of the E prostanoid(4) receptor by cyclic adenosine monophosphate production. Additionally, in comparison to previous studies, cyclooxygenase-2/prostaglandin E-2 related pro- and anti-inflammatory mediator regulation was partly confirmed in human lung tissue after pneumococcal infection. Overall, cell type-specific and MAPK-dependent cyclooxygenase-2 expression and prostaglandin E-2 formation in human lung tissue may play an important role in the early phase of pneumococcal infections. KW - Alveolar epithelial cells KW - cytokines KW - inflammation KW - lung infection KW - pneumonia KW - prostaglandins Y1 - 2012 U6 - https://doi.org/10.1183/09031936.00186911 SN - 0903-1936 VL - 40 IS - 6 SP - 1458 EP - 1467 PB - European Respiratory Society CY - Sheffield ER - TY - JOUR A1 - Wallmeyer, Leonie A1 - Dietert, Kristina A1 - Sochorova, Michaela A1 - Gruber, Achim D. A1 - Kleuser, Burkhard A1 - Vavrova, Katerina A1 - Hedtrich, Sarah T1 - TSLP is a direct trigger for T cell migration in filaggrin-deficient skin equivalents JF - Scientific reports N2 - Mutations in the gene encoding for filaggrin (FLG) are major predisposing factors for atopic dermatitis (AD). Besides genetic predisposition, immunological dysregulations considerably contribute to its pathophysiology. For example, thymic stromal lymphopoietin (TSLP) is highly expressed in lesional atopic skin and significantly contributes to the pathogenesis of AD by activating dendritic cells that then initiate downstream effects on, for example, T cells. However, little is known about the direct interplay between TSLP, filaggrin-deficient skin and other immune cells such as T lymphocytes. In the present study, FLG knockdown skin equivalents, characterised by intrinsically high TSLP levels, were exposed to activated CD4(+) T cells. T cell exposure resulted in an inflammatory phenotype of the skin equivalents. Furthermore, a distinct shift from a Th1/Th17 to a Th2/Th22 profile was observed following exposure of T cells to filaggrin-deficient skin equivalents. Interestingly, TSLP directly stimulated T cell migration exclusively in filaggrin-deficient skin equivalents even in the absence of dendritic cells, indicating a hitherto unknown role of TSLP in the pathogenesis of AD. Y1 - 2017 U6 - https://doi.org/10.1038/s41598-017-00670-2 SN - 2045-2322 VL - 7 PB - Nature Publ. Group CY - London ER -