TY  - JOUR
A1  - Doerck, Sebastian
A1  - Goebel, Kerstin
A1  - Weise, Gesa
A1  - Schneider-Hohendorf, Tilman
A1  - Reinhardt, Michael
A1  - Hauff, Peter
A1  - Schwab, Nicholas
A1  - Linker, Ralf
A1  - Maeurer, Mathias
A1  - Meuth, Sven G.
A1  - Wiendl, Heinz
T1  - Temporal Pattern of ICAM-I Mediated Regulatory T Cell Recruitment to Sites of Inflammation in Adoptive Transfer Model of Multiple Sclerosis
N2  - Migration of immune cells to the target organ plays a key role in autoimmune disorders like multiple sclerosis (MS). However, the exact underlying mechanisms of this active process during autoimmune lesion pathogenesis remain elusive. To test if pro-inflammatory and regulatory T cells migrate via a similar molecular mechanism, we analyzed the expression of different adhesion molecules, as well as the composition of infiltrating T cells in an in vivo model of MS, adoptive transfer experimental autoimmune encephalomyelitis in rats. We found that the upregulation of ICAM-I and VCAM-I parallels the development of clinical disease onset, but persists on elevated levels also in the phase of clinical remission. However, the composition of infiltrating T cells found in the developing versus resolving lesion phase changed over time, containing increased numbers of regulatory T cells (FoxP3) only in the phase of clinical remission. In order to test the relevance of the expression of cell adhesion molecules, animals were treated with purified antibodies to ICAM-I and VCAM-I either in the phase of active disease or in early remission. Treatment with a blocking ICAM-I antibody in the phase of disease progression led to a milder disease course. However, administration during early clinical remission aggravates clinical symptoms. Treatment with anti-VCAM-I at different timepoints had no significant effect on the disease course. In summary, our results indicate that adhesion molecules are not only important for capture and migration of pro-inflammatory T cells into the central nervous system, but also permit access of anti-inflammatory cells, such as regulatory T cells. Therefore it is likely to assume that intervention at the blood brain barrier is time dependent and could result in different therapeutic outcomes depending on the phase of CNS lesion development.
KW  - Multiple Sklerose
Y1  - 2010
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68565
ER  - 
TY  - JOUR
A1  - Lodde, Georg
A1  - Forschner, Andrea
A1  - Hassel, Jessica
A1  - Wulfken, Lena M.
A1  - Meier, Friedegund
A1  - Mohr, Peter
A1  - Kähler, Katharina
A1  - Schilling, Bastian
A1  - Loquai, Carmen
A1  - Berking, Carola
A1  - Hüning, Svea
A1  - Schatton, Kerstin
A1  - Gebhardt, Christoffer
A1  - Eckardt, Julia
A1  - Gutzmer, Ralf
A1  - Reinhardt, Lydia
A1  - Glutsch, Valerie
A1  - Nikfarjam, Ulrike
A1  - Erdmann, Michael
A1  - Stang, Andreas
A1  - Kowall, Bernd
A1  - Roesch, Alexander
A1  - Ugurel, Selma
A1  - Zimmer, Lisa
A1  - Schadendorf, Dirk
A1  - Livingstone, Elisabeth
T1  - Factors influencing the adjuvant therapy decision: results of a real-world multicenter data analysis of 904 melanoma patients
JF  - Cancers
N2  - Adjuvant treatment of melanoma patients with immune-checkpoint inhibition (ICI) and targeted therapy (TT) significantly improved recurrence-free survival. This study investigates the real-world situation of 904 patients from 13 German skin cancer centers with an indication for adjuvant treatment since the approval of adjuvant ICI and TT. From adjusted log-binomial regression models, we estimated relative risks for associations between various influence factors and treatment decisions (adjuvant therapy yes/no, TT vs. ICI in BRAF mutant patients). Of these patients, 76.9% (95% CI 74–80) opted for a systemic adjuvant treatment. The probability of starting an adjuvant treatment was 26% lower in patients >65 years (RR 0.74, 95% CI 68–80). The most common reasons against adjuvant treatment given by patients were age (29.4%, 95% CI 24–38), and fear of adverse events (21.1%, 95% CI 16–28) and impaired quality of life (11.9%, 95% CI 7–16). Of all BRAF-mutated patients who opted for adjuvant treatment, 52.9% (95% CI 47–59) decided for ICI. Treatment decision for TT or ICI was barely associated with age, gender and tumor stage, but with comorbidities and affiliated center. Shortly after their approval, adjuvant treatments have been well accepted by physicians and patients. Age plays a decisive role in the decision for adjuvant treatment, while pre-existing autoimmune disease and regional differences influence the choice between TT or ICI.
KW  - melanoma
KW  - adjuvant treatment
KW  - checkpoint blocker
KW  - targeted therapy
KW  - BRAF
KW  - PD-1
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239583
SN  - 2072-6694
VL  - 13
IS  - 10
ER  - 
TY  - JOUR
A1  - Benoit, Joshua B.
A1  - Adelman, Zach N.
A1  - Reinhardt, Klaus
A1  - Dolan, Amanda
A1  - Poelchau, Monica
A1  - Jennings, Emily C.
A1  - Szuter, Elise M.
A1  - Hagan, Richard W.
A1  - Gujar, Hemant
A1  - Shukla, Jayendra Nath
A1  - Zhu, Fang
A1  - Mohan, M.
A1  - Nelson, David R.
A1  - Rosendale, Andrew J.
A1  - Derst, Christian
A1  - Resnik, Valentina
A1  - Wernig, Sebastian
A1  - Menegazzi, Pamela
A1  - Wegener, Christian
A1  - Peschel, Nicolai
A1  - Hendershot, Jacob M.
A1  - Blenau, Wolfgang
A1  - Predel, Reinhard
A1  - Johnston, Paul R.
A1  - Ioannidis, Panagiotis
A1  - Waterhouse, Robert M.
A1  - Nauen, Ralf
A1  - Schorn, Corinna
A1  - Ott, Mark-Christoph
A1  - Maiwald, Frank
A1  - Johnston, J. Spencer
A1  - Gondhalekar, Ameya D.
A1  - Scharf, Michael E.
A1  - Raje, Kapil R.
A1  - Hottel, Benjamin A.
A1  - Armisén, David
A1  - Crumière, Antonin Jean Johan
A1  - Refki, Peter Nagui
A1  - Santos, Maria Emilia
A1  - Sghaier, Essia
A1  - Viala, Sèverine
A1  - Khila, Abderrahman
A1  - Ahn, Seung-Joon
A1  - Childers, Christopher
A1  - Lee, Chien-Yueh
A1  - Lin, Han
A1  - Hughes, Daniel S.T.
A1  - Duncan, Elizabeth J.
A1  - Murali, Shwetha C.
A1  - Qu, Jiaxin
A1  - Dugan, Shannon
A1  - Lee, Sandra L.
A1  - Chao, Hsu
A1  - Dinh, Huyen
A1  - Han, Yi
A1  - Doddapaneni, Harshavardhan
A1  - Worley, Kim C.
A1  - Muzny, Donna M.
A1  - Wheeler, David
A1  - Panfilio, Kristen A.
A1  - Jentzsch, Iris M. Vargas
A1  - Jentzsch, IMV
A1  - Vargo, Edward L.
A1  - Booth, Warren
A1  - Friedrich, Markus
A1  - Weirauch, Matthew T.
A1  - Anderson, Michelle A.E.
A1  - Jones, Jeffery W.
A1  - Mittapalli, Omprakash
A1  - Zhao, Chaoyang
A1  - Zhou, Jing-Jiang
A1  - Evans, Jay D.
A1  - Attardo, Geoffrey M.
A1  - Robertson, Hugh M.
A1  - Zdobnov, Evgeny M.
A1  - Ribeiro, Jose M.C.
A1  - Gibbs, Richard A.
A1  - Werren, John H.
A1  - Palli, Subba R.
A1  - Schal, Coby
A1  - Richards, Stephen
T1  - Unique features of a global human ectoparasite identified through sequencing of the bed bug genome
JF  - Nature Communications
N2  - The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host–symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome sequencing and annotation establish a solid foundation for future research on mechanisms of insecticide resistance, human–bed bug and symbiont–bed bug associations, and unique features of bed bug biology that contribute to the unprecedented success of C. lectularius as a human ectoparasite.
KW  - human ectoparasite
KW  - bed bug
KW  - Cimex lectularius
KW  - genome
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166221
VL  - 7
IS  - 10165
ER  - 
TY  - JOUR
A1  - Massih, Bita
A1  - Veh, Alexander
A1  - Schenke, Maren
A1  - Mungwa, Simon
A1  - Seeger, Bettina
A1  - Selvaraj, Bhuvaneish T.
A1  - Chandran, Siddharthan
A1  - Reinhardt, Peter
A1  - Sterneckert, Jared
A1  - Hermann, Andreas
A1  - Sendtner, Michael
A1  - Lüningschrör, Patrick
T1  - A 3D cell culture system for bioengineering human neuromuscular junctions to model ALS
JF  - Frontiers in Cell and Developmental Biology
N2  - The signals that coordinate and control movement in vertebrates are transmitted from motoneurons (MNs) to their target muscle cells at neuromuscular junctions (NMJs). Human NMJs display unique structural and physiological features, which make them vulnerable to pathological processes. NMJs are an early target in the pathology of motoneuron diseases (MND). Synaptic dysfunction and synapse elimination precede MN loss suggesting that the NMJ is the starting point of the pathophysiological cascade leading to MN death. Therefore, the study of human MNs in health and disease requires cell culture systems that enable the connection to their target muscle cells for NMJ formation. Here, we present a human neuromuscular co-culture system consisting of induced pluripotent stem cell (iPSC)-derived MNs and 3D skeletal muscle tissue derived from myoblasts. We used self-microfabricated silicone dishes combined with Velcro hooks to support the formation of 3D muscle tissue in a defined extracellular matrix, which enhances NMJ function and maturity. Using a combination of immunohistochemistry, calcium imaging, and pharmacological stimulations, we characterized and confirmed the function of the 3D muscle tissue and the 3D neuromuscular co-cultures. Finally, we applied this system as an in vitro model to study the pathophysiology of Amyotrophic Lateral Sclerosis (ALS) and found a decrease in neuromuscular coupling and muscle contraction in co-cultures with MNs harboring ALS-linked SOD1 mutation. In summary, the human 3D neuromuscular cell culture system presented here recapitulates aspects of human physiology in a controlled in vitro setting and is suitable for modeling of MND.
KW  - NMJ–neuromuscular junction
KW  - motoneuron (MN)
KW  - skeletal muscle
KW  - iPSC (induced pluripotent stem cells)
KW  - 3D cell culture
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304161
SN  - 2296-634X
VL  - 11
ER  -