@phdthesis{Westfahl2020, author = {Westfahl, Larissa}, title = {Influenza-assoziierte Hospitalisierungen bei Kindern und Erwachsenen am Universit{\"a}tsklinikum W{\"u}rzburg in den Jahren 2010-2013}, doi = {10.25972/OPUS-19990}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-199907}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2020}, abstract = {Influenza-assoziierte Atemwegserkrankungen f{\"u}hren jedes Jahr zu zahlreichen Hospitalisierungen und Todesf{\"a}llen. Der w{\"a}hrend der Pandemie 2009 zirkulierende Erreger Influenza A(H1N1)pdm09 f{\"u}hrte zu zahlreichen, zum Teil schweren Komplikationen, insbesondere auch bei j{\"u}ngeren Erwachsenen. In der vorliegenden Studie wurden Influenza-assoziierte Hospitalisierungen (IAH) hinsichtlich Krankheitsverlauf in den verschiedenen Altersgruppen sowie bei verschiedenen Erregern untersucht. Zudem erfolgte eine Analyse der direkten Krankheitskosten. Einen besonders schweren Verlauf zeigten Erwachsene mit Grunderkrankung zwischen 18-60 Jahren, die {\"u}berwiegend mit dem Erreger Influenza A(H1N1)pdm09 infiziert waren. Ebenso waren schwangeren Patientinnen mit IAH mit dem Erreger A(H1N1)pdm09 selten, aber schwer betroffen. Bei Patienten von 18-60 Jahren mit dem Erreger Influenza A(H1N1)pdm09 entstanden die h{\"o}chsten direkten Kosten im Vergleich zu den anderen Altersgruppen.}, subject = {Influenza}, language = {de} } @article{KuehnemundtLeifeldSchergetal.2021, author = {K{\"u}hnemundt, Johanna and Leifeld, Heidi and Scherg, Florian and Schmitt, Matthias and Nelke, Lena C. and Schmitt, Tina and Bauer, Florentin and G{\"o}ttlich, Claudia and Fuchs, Maximilian and Kunz, Meik and Peindl, Matthias and Br{\"a}hler, Caroline and Kronenthaler, Corinna and Wischhusen, J{\"o}rg and Prelog, Martina and Walles, Heike and Dandekar, Thomas and Dandekar, Gudrun and Nietzer, Sarah L.}, title = {Modular micro-physiological human tumor/tissue models based on decellularized tissue for improved preclinical testing}, series = {ALTEX}, volume = {38}, journal = {ALTEX}, doi = {10.14573/altex.2008141}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231465}, pages = {289-306}, year = {2021}, abstract = {High attrition-rates entailed by drug testing in 2D cell culture and animal models stress the need for improved modeling of human tumor tissues. In previous studies our 3D models on a decellularized tissue matrix have shown better predictivity and higher chemoresistance. A single porcine intestine yields material for 150 3D models of breast, lung, colorectal cancer (CRC) or leukemia. The uniquely preserved structure of the basement membrane enables physiological anchorage of endothelial cells and epithelial-derived carcinoma cells. The matrix provides different niches for cell growth: on top as monolayer, in crypts as aggregates and within deeper layers. Dynamic culture in bioreactors enhances cell growth. Comparing gene expression between 2D and 3D cultures, we observed changes related to proliferation, apoptosis and stemness. For drug target predictions, we utilize tumor-specific sequencing data in our in silico model finding an additive effect of metformin and gefitinib treatment for lung cancer in silico, validated in vitro. To analyze mode-of-action, immune therapies such as trispecific T-cell engagers in leukemia, as well as toxicity on non-cancer cells, the model can be modularly enriched with human endothelial cells (hECs), immune cells and fibroblasts. Upon addition of hECs, transmigration of immune cells through the endothelial barrier can be investigated. In an allogenic CRC model we observe a lower basic apoptosis rate after applying PBMCs in 3D compared to 2D, which offers new options to mirror antigen-specific immunotherapies in vitro. In conclusion, we present modular human 3D tumor models with tissue-like features for preclinical testing to reduce animal experiments.}, language = {en} } @phdthesis{HilligardtgebRueck2021, author = {Hilligardt [geb. R{\"u}ck], Deborah}, title = {Methylierung pro- und antiinflammatorischer T-Helfer-Zell-spezifischer Transkriptionsfaktoren bei ausgew{\"a}hlten Krankheitsbildern}, doi = {10.25972/OPUS-24949}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-249499}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {Die Regulation krankheitsrelevanter Gene und deren Proteine {\"u}ber Ver{\"a}nderungen in der DNA-Methylierung stellen einen wichtigen und zugleich noch unzureichend erforschten Bereich bei Erkrankungen mit inflammatorischer Komponente dar. In dieser Arbeit wurde die Methylierung pro- und antiinflammatorischer Gene im hypoxischen Setting hervorgerufen durch Pr{\"a}eklampsie, Angsterkrankung und Inflammation bei Sklerodermie untersucht. Zur Bestimmung der prozentualen Methylierung wurde Pyrosequenzierung durchgef{\"u}hrt. Bei einem Teil der Proben erfolgte zus{\"a}tzlich die Bestimmung der Genexpression mittels Real Time PCR. Bei Angsterkrankung zeigte sich eine signifikante Hypermethylierung am Promotor des Treg spezifischen Transkriptionsfaktors FOXP3. Daraus k{\"o}nnte eine beeintr{\"a}chtigte Funktion der Tregs und somit eine erh{\"o}hte Komorbidit{\"a}t resultieren. In der Gruppe der an Sklerodermie erkrankten Personen zeigte sich entgegen den Erwartungen eine signifikant h{\"o}here RORC1 und RORC2 Methylierung. Eine Genexpressionsanalyse erbrachte eine signifikant niedrigere Expression von RORC bei Sklerodermie im Vergleich zu gesunden Kontrollen. Diese {\"u}berraschenden Ergebnisse k{\"o}nnten der Methodik geschuldet sein. Auf eine Auftrennung der verschiedenen T-Zellen vor Messung der Methylierung wurde verzichtet. Plazentagewebe bei Pr{\"a}eklampsie zeigte eine signifikant geringere Methylierung am FOXP3 Promotor als Plazentagewebe von gesunden Schwangeren. Die Ver{\"a}nderbarkeit der DNA-Methylierung durch {\"a}ußere Einfl{\"u}sse und Medikamente stellt hierbei einen vielversprechenden Ansatzpunkt f{\"u}r zuk{\"u}nftige Therapien dar und sollte in weiteren Studien konkretisiert werden.}, subject = {Methylierung}, language = {de} } @article{ScheerVokuhlBlanketal.2019, author = {Scheer, Monika and Vokuhl, Christian and Blank, Bernd and Hallmen, Erika and von Kalle, Thekla and M{\"u}nter, Marc and Wessalowski, R{\"u}diger and Hartwig, Maite and Sparber-Sauer, Monika and Schlegel, Paul-Gerhardt and Kramm, Christof M. and Kontny, Udo and Spriewald, Bernd and Kegel, Thomas and Bauer, Sebastian and Kazanowska, Bernarda and Niggli, Felix and Ladenstein, Ruth and Ljungman, Gustaf and Jahnukainen, Kirsi and Fuchs, J{\"o}rg and Bielack, Stefan S. and Klingebiel, Thomas and Koscielniak, Ewa}, title = {Desmoplastic small round cell tumors: Multimodality treatment and new risk factors}, series = {Cancer Medicine}, volume = {8}, journal = {Cancer Medicine}, number = {2}, doi = {10.1002/cam4.1940}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228444}, pages = {527-545}, year = {2019}, abstract = {Background To evaluate optimal therapy and potential risk factors. Methods Data of DSRCT patients <40 years treated in prospective CWS trials 1997-2015 were analyzed. Results Median age of 60 patients was 14.5 years. Male:female ratio was 4:1. Tumors were abdominal/retroperitoneal in 56/60 (93\%). 6/60 (10\%) presented with a localized mass, 16/60 (27\%) regionally disseminated nodes, and 38/60 (63\%) with extraperitoneal metastases. At diagnosis, 23/60 (38\%) patients had effusions, 4/60 (7\%) a thrombosis, and 37/54 (69\%) elevated CRP. 40/60 (67\%) patients underwent tumor resection, 21/60 (35\%) macroscopically complete. 37/60 (62\%) received chemotherapy according to CEVAIE (ifosfamide, vincristine, actinomycin D, carboplatin, epirubicin, etoposide), 15/60 (25\%) VAIA (ifosfamide, vincristine, adriamycin, actinomycin D) and, 5/60 (8\%) P6 (cyclophosphamide, doxorubicin, vincristine, ifosfamide, etoposide). Nine received high-dose chemotherapy, 6 received regional hyperthermia, and 20 received radiotherapy. Among 25 patients achieving complete remission, 18 (72\%) received metronomic therapies. Three-year event-free (EFS) and overall survival (OS) were 11\% (±8 confidence interval [CI] 95\%) and 30\% (±12 CI 95\%), respectively, for all patients and 26.7\% (±18.0 CI 95\%) and 56.9\% (±20.4 CI 95\%) for 25 patients achieving remission. Extra-abdominal site, localized disease, no effusion or ascites only, absence of thrombosis, normal CRP, complete tumor resection, and chemotherapy with VAIA correlated with EFS in univariate analysis. In multivariate analysis, significant factors were no thrombosis and chemotherapy with VAIA. In patients achieving complete remission, metronomic therapy with cyclophosphamide/vinblastine correlated with prolonged time to relapse. Conclusion Pleural effusions, venous thrombosis, and CRP elevation were identified as potential risk factors. The VAIA scheme showed best outcome. Maintenance therapy should be investigated further.}, language = {en} } @article{SilwedelSpeerHaarmannetal.2018, author = {Silwedel, Christine and Speer, Christian P. and Haarmann, Axel and Fehrholz, Markus and Claus, Heike and Buttmann, Mathias and Glaser, Kirsten}, title = {Novel insights into neuroinflammation: bacterial lipopolysaccharide, tumor necrosis factor α, and Ureaplasma species differentially modulate atypical chemokine receptor 3 responses in human brain microvascular endothelial cells}, series = {Journal of Neuroinflammation}, volume = {15}, journal = {Journal of Neuroinflammation}, number = {156}, doi = {10.1186/s12974-018-1170-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175952}, year = {2018}, abstract = {Background: Atypical chemokine receptor 3 (ACKR3, synonym CXCR7) is increasingly considered relevant in neuroinflammatory conditions, in which its upregulation contributes to compromised endothelial barrier function and may ultimately allow inflammatory brain injury. While an impact of ACKR3 has been recognized in several neurological autoimmune diseases, neuroinflammation may also result from infectious agents, including Ureaplasma species (spp.). Although commonly regarded as commensals of the adult urogenital tract, Ureaplasma spp. may cause invasive infections in immunocompromised adults as well as in neonates and appear to be relevant pathogens in neonatal meningitis. Nonetheless, clinical and in vitro data on Ureaplasma-induced inflammation are scarce. Methods: We established a cell culture model of Ureaplasma meningitis, aiming to analyze ACKR3 variances as a possible pathomechanism in Ureaplasma-associated neuroinflammation. Non-immortalized human brain microvascular endothelial cells (HBMEC) were exposed to bacterial lipopolysaccharide (LPS) or tumor necrosis factor-α (TNF-α), and native as well as LPS-primed HBMEC were cultured with Ureaplasma urealyticum serovar 8 (Uu8) and U. parvum serovar 3 (Up3). ACKR3 responses were assessed via qRT-PCR, RNA sequencing, flow cytometry, and immunocytochemistry. Results: LPS, TNF-α, and Ureaplasma spp. influenced ACKR3 expression in HBMEC. LPS and TNF-α significantly induced ACKR3 mRNA expression (p < 0.001, vs. control), whereas Ureaplasma spp. enhanced ACKR3 protein expression in HBMEC (p < 0.01, vs. broth control). Co-stimulation with LPS and either Ureaplasma isolate intensified ACKR3 responses (p < 0.05, vs. LPS). Furthermore, stimulation wielded a differential influence on the receptor's ligands. Conclusions: We introduce an in vitro model of Ureaplasma meningitis. We are able to demonstrate a pro-inflammatory capacity of Ureaplasma spp. in native and, even more so, in LPS-primed HBMEC, underlining their clinical relevance particularly in a setting of co-infection. Furthermore, our data may indicate a novel role for ACKR3, with an impact not limited to auto-inflammatory diseases, but extending to infection-related neuroinflammation as well. AKCR3-induced blood-brain barrier breakdown might constitute a potential common pathomechanism.}, language = {en} } @article{FioreVaccaTuminoetal.2021, author = {Fiore, Piera Filomena and Vacca, Paola and Tumino, Nicola and Besi, Francesca and Pelosi, Andrea and Munari, Enrico and Marconi, Marcella and Caruana, Ignazio and Pistoia, Vito and Moretta, Lorenzo and Azzarone, Bruno}, title = {Wilms' tumor primary cells display potent immunoregulatory properties on NK cells and macrophages}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {2}, issn = {2072-6694}, doi = {10.3390/cancers13020224}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222981}, year = {2021}, abstract = {The immune response plays a crucial defensive role in cancer growth and metastasis and is a promising target in different tumors. The role of the immune system in Wilm's Tumor (WT), a common pediatric renal malignancy, is still to be explored. The characterization of the immune environment in WT could allow the identification of new therapeutic strategies for targeting possible inhibitory mechanisms and/or lowering toxicity of the current treatments. In this study, we stabilized four WT primary cultures expressing either a blastematous (CD56\(^+\)/CD133\(^-\)) or an epithelial (CD56\(^-\)/CD133\(^+\)) phenotype and investigated their interactions with innate immune cells, namely NK cells and monocytes. We show that cytokine-activated NK cells efficiently kill WT cells. However, after co-culture with WT primary cells, NK cells displayed an impaired cytotoxic activity, decreased production of IFNγ and expression of CD107a, DNAM-1 and NKp30. Analysis of the effects of the interaction between WT cells and monocytes revealed their polarization towards alternatively activated macrophages (M2) that, in turn, further impaired NK cell functions. In conclusion, we show that both WT blastematous and epithelial components may contribute directly and indirectly to a tumor immunosuppressive microenvironment that is likely to play a role in tumor progression.}, language = {en} } @article{RufBeerKoestleretal.2019, author = {Ruf, Katharina and Beer, Meinrad and K{\"o}stler, Herbert and Weng, Andreas Max and Neubauer, Henning and Klein, Alexander and Platek, Kathleen and Roth, Kristina and Beneke, Ralph and Hebestreit, Helge}, title = {Size-adjusted muscle power and muscle metabolism in patients with cystic fibrosis are equal to healthy controls - a case control study}, series = {BMC Pulmonary Medicine}, volume = {19}, journal = {BMC Pulmonary Medicine}, doi = {10.1186/s12890-019-1039-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200981}, pages = {269}, year = {2019}, abstract = {Background Skeletal muscle function dysfunction has been reported in patients with cystic fibrosis (CF). Studies so far showed inconclusive data whether reduced exercise capacity is related to intrinsic muscle dysfunction in CF. Methods Twenty patients with CF and 23 age-matched controls completed an incremental cardiopulmonary cycling test. Further, a Wingate anaerobic test to assess muscle power was performed. In addition, all participants completed an incremental knee-extension test with 31P magnetic resonance spectroscopy to assess muscle metabolism (inorganic phosphate (Pi) and phosphocreatinine (PCr) as well as intracellular pH). In the MRI, muscle cross-sectional area of the M. quadriceps (qCSA) was also measured. A subgroup of 15 participants (5 CF, 10 control) additionally completed a continuous high-intensity, high-frequency knee-extension exercise task during 31P magnetic resonance spectroscopy to assess muscle metabolism. Results Patients with CF showed a reduced exercise capacity in the incremental cardiopulmonary cycling test (VO2peak: CF 77.8 ± 16.2\%predicted (36.5 ± 7.4 ml/qCSA/min), control 100.6 ± 18.8\%predicted (49.1 ± 11.4 ml/qCSA/min); p < 0.001), and deficits in anaerobic capacity reflected by the Wingate test (peak power: CF 537 ± 180 W, control 727 ± 186 W; mean power: CF 378 ± 127 W, control 486 ± 126 W; power drop CF 12 ± 5 W, control 8 ± 4 W. all: p < 0.001). In the knee-extension task, patients with CF achieved a significantly lower workload (p < 0.05). However, in a linear model analysing maximal work load of the incremental knee-extension task and results of the Wingate test, respectively, only muscle size and height, but not disease status (CF or not) contributed to explaining variance. In line with this finding, no differences were found in muscle metabolism reflected by intracellular pH and the ratio of Pi/PCr at submaximal stages and peak exercise measured through MRI spectroscopy. Conclusions The lower absolute muscle power in patients with CF compared to controls is exclusively explained by the reduced muscle size in this study. No evidence was found for an intrinsic skeletal muscle dysfunction due to primary alterations of muscle metabolism.}, language = {en} } @article{FehrholzGlaserSpeeretal.2017, author = {Fehrholz, Markus and Glaser, Kirsten and Speer, Christian P. and Seidenspinner, Silvia and Ottensmeier, Barbara and Kunzmann, Steffen}, title = {Caffeine modulates glucocorticoid-induced expression of CTGF in lung epithelial cells and fibroblasts}, series = {Respiratory Research}, volume = {18}, journal = {Respiratory Research}, number = {51}, doi = {10.1186/s12931-017-0535-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157672}, year = {2017}, abstract = {Background: Although caffeine and glucocorticoids are frequently used to treat chronic lung disease in preterm neonates, potential interactions are largely unknown. While anti-inflammatory effects of glucocorticoids are well defined, their impact on airway remodeling is less characterized. Caffeine has been ascribed to positive effects on airway inflammation as well as remodeling. Connective tissue growth factor (CTGF, CCN2) plays a key role in airway remodeling and has been implicated in the pathogenesis of chronic lung diseases such as bronchopulmonary dysplasia (BPD) in preterm infants. The current study addressed the impact of glucocorticoids on the regulation of CTGF in the presence of caffeine using human lung epithelial and fibroblast cells. Methods: The human airway epithelial cell line H441 and the fetal lung fibroblast strain IMR-90 were exposed to different glucocorticoids (dexamethasone, budesonide, betamethasone, prednisolone, hydrocortisone) and caffeine. mRNA and protein expression of CTGF, TGF-β1-3, and TNF-α were determined by means of quantitative real-time PCR and immunoblotting. H441 cells were additionally treated with cAMP, the adenylyl cyclase activator forskolin, and the selective phosphodiesterase (PDE)-4 inhibitor cilomilast to mimic caffeine-mediated PDE inhibition. Results: Treatment with different glucocorticoids (1 μM) significantly increased CTGF mRNA levels in H441 (p < 0.0001) and IMR-90 cells (p < 0.01). Upon simultaneous exposure to caffeine (10 mM), both glucocorticoid-induced mRNA and protein expression were significantly reduced in IMR-90 cells (p < 0.0001). Of note, 24 h exposure to caffeine alone significantly suppressed basal expression of CTGF mRNA and protein in IMR-90 cells. Caffeine-induced reduction of CTGF mRNA expression seemed to be independent of cAMP levels, adenylyl cyclase activation, or PDE-4 inhibition. While dexamethasone or caffeine treatment did not affect TGF-β1 mRNA in H441 cells, increased expression of TGF-β2 and TGF-β3 mRNA was detected upon exposure to dexamethasone or dexamethasone and caffeine, respectively. Moreover, caffeine increased TNF-α mRNA in H441 cells (6.5 ± 2.2-fold, p < 0.05) which has been described as potent inhibitor of CTGF expression. Conclusions: In addition to well-known anti-inflammatory features, glucocorticoids may have adverse effects on long-term remodeling by TGF-β1-independent induction of CTGF in lung cells. Simultaneous treatment with caffeine may attenuate glucocorticoid-induced expression of CTGF, thereby promoting restoration of lung homeostasis.}, language = {en} } @article{NothhaftKlepperKneitzetal.2019, author = {Nothhaft, Matthias and Klepper, Joerg and Kneitz, Hermann and Meyer, Thomas and Hamm, Henning and Morbach, Henner}, title = {Hemorrhagic bullous Henoch-Sch{\"o}nlein Purpura: case report and review of the literature}, series = {Frontiers in Pediatrics}, volume = {6}, journal = {Frontiers in Pediatrics}, doi = {10.3389/fped.2018.00413}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201435}, pages = {413}, year = {2019}, abstract = {Henoch-Sch{\"o}nlein Purpura (HSP) or IgA vasculitis is the most common systemic vasculitis of childhood and may affect skin, joints, gastrointestinal tract, and kidneys. Skin manifestations of HSP are characteristic and include a non-thrombocytopenic palpable purpura of the lower extremities and buttocks. Rarely, HSP may initially present as or evolve into hemorrhagic vesicles and bullae. We present an otherwise healthy 5-year-old boy with an acute papulovesicular rash of both legs and intermittent abdominal pain. After a few days the skin lesions rapidly evolved into palpable purpura and hemorrhagic bullous lesions of variable size and severe hemorrhagic HSP was suspected. A histological examination of a skin biopsy showed signs of a small vessel leukocytoclastic vasculitis limited to the upper dermis and direct immunofluorescence analysis revealed IgA deposits in vessel walls, compatible with HSP. To further characterize the clinical picture and treatment options of bullous HSP we performed an extensive literature research and identified 41 additional pediatric patients with bullous HSP. Two thirds of the reported patients were treated with systemic corticosteroids, however, up to 25\% of the reported patients developed skin sequelae such as hyperpigmentation and/or scarring. The early use of systemic corticosteroids has been discussed controversially and suggested in some case series to be beneficial by reducing the extent of lesions and minimizing sequelae of disease. Our patient was treated with systemic corticosteroids tapered over 5 weeks. Fading of inflammation resulted in healing of most erosions, however, a deep necrosis developing from a large blister at the dorsum of the right foot persisted so that autologous skin transplantation was performed. Re-examination 11 months after disease onset showed complete clinical remission with re-epithelialization but also scarring of some affected areas.}, language = {en} } @phdthesis{Krakow2021, author = {Krakow, S{\"o}ren}, title = {CD14-Reexpression definiert einen immunregulatorischen Phänotyp Monozyten-gereifter Zellen nach IL-10/R848-Stimulation}, doi = {10.25972/OPUS-22428}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224280}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {Dendritische Zellen k{\"o}nnen als antigenpr{\"a}sentierende Zellen sowohl immunogene als auch tolerogene Funktionen im Immunsystem wahrnehmen und werden in der Therapie von Tumorerkrankungen und Autoimmunerkrankungen eingesetzt. IL-10 gilt als Induktor tolerogener dendritischer Zellen. Diese werden in der Literatur oft als unreif bezeichnet und stehen im Gegensatz zu den reifen immunogenen dendritischen Zellen, die durch die Expression des Reifungsmarkers CD83 gekennzeichnet sind. Ausdifferenzierte dendritische Zellen exprimieren zudem das Antigen CD86, das der T-Zell-Aktivierung dient. In der vorliegenden Arbeit wurde der Einfluss von IL-10 auf den Reifungsprozess dendritischer Zellen in vitro untersucht. Zur Generierung unreifer dendritischer Zellen wurden humane Monozyten nach etabliertem Protokoll mit IL-4 und GM-CSF stimuliert. Nach anschließender IL-10-Stimulation, insbesondere in Kombination mit einem TLR-Agonisten, bildeten sich zwei exklusive Zellpopulationen: eine CD14+ Population und eine CD83+ Population. Unreife CD14-CD83- dendritische Zellen reexprimierten einerseits CD14 oder exprimierten andererseits CD83. Dabei zeigte sich, dass das kostimulierende Antigen CD86 gleichermaßen sowohl mit als auch ohne IL-10-Inkubation hoch exprimiert wurde und IL-10 folglich keinen zus{\"a}tzlichen Einfluss auf dessen Expression hat. Insgesamt waren Ver{\"a}nderungen bez{\"u}glich der Oberfl{\"a}chenantigene, die bei der Betrachtung der Gesamtheit aller Zellen auffallen, auf eine quantitative Verschiebung der beiden Zellpopulationen zur{\"u}ckzuf{\"u}hren. IL-10 beeinflusst also nicht direkt einzelne kostimulierende oder inhibitorische Molek{\"u}le, sondern beeinflusst den Anteil der CD14+ Zellen gegen{\"u}ber den CD83+ dendritischen Zellen. Funktionell betrachtet zeigten die CD14+ Zellen eine gesteigerte Makropinozytose im Gegensatz zu den reifen CD83+ dendritischen Zellen. Zusammenfassend f{\"u}hrt IL-10 zu einer Reexpression von CD14 auf unreifen dendritischen Zellen und aktiviert einen alternativen Differenzierungsweg. Die CD14+ Zellen weisen einen stabilen immunregulatorischen Ph{\"a}notyp auf und unterscheiden sich somit von reifen dendritischen Zellen, die nach Inkubation mit IL-10 nicht reguliert werden. Damit muss die Begrifflichkeit und Klassifikation tolerogener dendritischer Zellen weiter diskutiert werden.}, subject = {Dendritische Zelle}, language = {de} }