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Croxford and IL-6

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https://www.readbyqxmd.com/read/27893700/trans-presentation-of-il-6-by-dendritic-cells-is-required-for-the-priming-of-pathogenic-th17-cells
#1
Sylvia Heink, Nir Yogev, Christoph Garbers, Marina Herwerth, Lilian Aly, Christiane Gasperi, Veronika Husterer, Andrew L Croxford, Katja Möller-Hackbarth, Harald S Bartsch, Karl Sotlar, Stefan Krebs, Tommy Regen, Helmut Blum, Bernhard Hemmer, Thomas Misgeld, Thomas F Wunderlich, Juan Hidalgo, Mohamed Oukka, Stefan Rose-John, Marc Schmidt-Supprian, Ari Waisman, Thomas Korn
The cellular sources of interleukin 6 (IL-6) that are relevant for differentiation of the TH17 subset of helper T cells remain unclear. Here we used a novel strategy for the conditional deletion of distinct IL-6-producing cell types to show that dendritic cells (DCs) positive for the signaling regulator Sirpα were essential for the generation of pathogenic TH17 cells. Using their IL-6 receptor α-chain (IL-6Rα), Sirpα(+) DCs trans-presented IL-6 to T cells during the process of cognate interaction. While ambient IL-6 was sufficient to suppress the induction of expression of the transcription factor Foxp3 in T cells, trans-presentation of IL-6 by DC-bound IL-6Rα (called 'IL-6 cluster signaling' here) was needed to prevent premature induction of interferon-γ (IFN-γ) expression in T cells and to generate pathogenic TH17 cells in vivo...
November 28, 2016: Nature Immunology
https://www.readbyqxmd.com/read/25341795/interleukin-17-drives-vascular-inflammation-endothelial-dysfunction-and-arterial-hypertension-in-psoriasis-like-skin-disease
#2
Susanne Karbach, Andrew L Croxford, Matthias Oelze, Rebecca Schüler, Daniel Minwegen, Joanna Wegner, Lija Koukes, Nir Yogev, Alexei Nikolaev, Sonja Reißig, Alexander Ullmann, Maike Knorr, Maximilian Waldner, Markus F Neurath, Huige Li, Zhixiong Wu, Christoph Brochhausen, Jürgen Scheller, Stefan Rose-John, Carolin Piotrowski, Ingo Bechmann, Markus Radsak, Philipp Wild, Andreas Daiber, Esther von Stebut, Philip Wenzel, Ari Waisman, Thomas Münzel
OBJECTIVE: Interleukin (IL)-17A is regarded as an important cytokine to drive psoriasis, an inflammatory skin disease marked by increased cardiovascular mortality. We aimed to test the hypothesis that overproduction of IL-17A in the skin leading to dermal inflammation may systemically cause vascular dysfunction in psoriasis-like skin disease. APPROACH AND RESULTS: Conditional overexpression of IL-17A in keratinocytes caused severe psoriasis-like skin inflammation in mice (K14-IL-17A(ind/+) mice), associated with increased reactive oxygen species formation and circulating CD11b(+) inflammatory leukocytes in blood, with endothelial dysfunction, increased systolic blood pressure, left ventricular hypertrophy, and reduced survival compared with controls...
December 2014: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/24067382/il-6-regulates-neutrophil-microabscess-formation-in-il-17a-driven-psoriasiform-lesions
#3
Andrew L Croxford, Susanne Karbach, Florian C Kurschus, Simone Wörtge, Alexei Nikolaev, Nir Yogev, Sabrina Klebow, Rebecca Schüler, Sonja Reissig, Carolin Piotrowski, Elke Brylla, Ingo Bechmann, Jürgen Scheller, Stefan Rose-John, F Thomas Wunderlich, Thomas Münzel, Esther von Stebut, Ari Waisman
The lack of a generally accepted animal model for human psoriasis has hindered progress with respect to understanding the pathogenesis of the disease. Here we present a model in which transgenic IL-17A expression is targeted to the skin in mice, achievable after crossing our IL-17A(ind) allele to the K14-Cre strain. K14-IL-17A(ind/+) mice invariably develop an overt skin inflammation bearing many hallmark characteristics of human psoriasis including dermal infiltration of effector T cells, formation of neutrophil microabscesses, and hyperkeratosis...
March 2014: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/19940258/cellular-mechanisms-of-il-17-induced-blood-brain-barrier-disruption
#4
Jula Huppert, Dorothea Closhen, Andrew Croxford, Robin White, Paulina Kulig, Eweline Pietrowski, Ingo Bechmann, Burkhard Becher, Heiko J Luhmann, Ari Waisman, Christoph R W Kuhlmann
Recently T-helper 17 (Th17) cells were demonstrated to disrupt the blood-brain barrier (BBB) by the action of IL-17A. The aim of the present study was to examine the mechanisms that underlie IL-17A-induced BBB breakdown. Barrier integrity was analyzed in the murine brain endothelial cell line bEnd.3 by measuring the electrical resistance values using electrical call impedance sensing technology. Furthermore, in-cell Western blots, fluorescence imaging, and monocyte adhesion and transendothelial migration assays were performed...
April 2010: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/19620309/suppression-of-experimental-autoimmune-encephalomyelitis-by-ghrelin
#5
Michael-Mark Theil, Sachiko Miyake, Miho Mizuno, Chiharu Tomi, J Ludovic Croxford, Hiroshi Hosoda, Julia Theil, Stephan von Hörsten, Hiroaki Yokote, Asako Chiba, Youwei Lin, Shinji Oki, Takashi Akamizu, Kenji Kangawa, Takashi Yamamura
Ghrelin is a recently identified gastric hormone that displays strong growth hormone-releasing activity mediated by the growth hormone secretagogue receptor. While this unique endogenous peptide participates in the regulation of energy homeostasis, increases food intake, and decreases energy expenditure, its ability to inhibit the production of proinflammatory cytokines in vitro indicates its role in the regulation of inflammatory process in vivo. Here we examine the effect of exogenous ghrelin on the development of experimental autoimmune encephalomyelitis (EAE), a representative model of multiple sclerosis...
August 15, 2009: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/19155467/cutting-edge-an-il-17f-creeyfp-reporter-mouse-allows-fate-mapping-of-th17-cells
#6
Andrew L Croxford, Florian C Kurschus, Ari Waisman
The need for reporter lines able to faithfully track Th17 cells in vivo has become an issue of exceptional importance. To address this, we generated a mouse strain in which Cre recombinase is expressed from the IL-17F promoter. Crossing the IL-17F-Cre allele to a conditional enhanced yellow fluorescent protein (EYFP) reporter mouse yielded the IL-17F-Cre(EYFP) strain, in which IL-17F expression is twinned with EYFP in live IL-17F-expressing cells. Although we demonstrate that IL-17F expression is restricted to CD4(+) T cells during experimental autoimmune encephalomyelitis, IL-17F-Cre(EYFP) CD8 T cells robustly expressed IL-17F in response to TGF-beta, IL-6, and IL-23...
February 1, 2009: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/19015529/il-6-controls-th17-immunity-in-vivo-by-inhibiting-the-conversion-of-conventional-t-cells-into-foxp3-regulatory-t-cells
#7
Thomas Korn, Meike Mitsdoerffer, Andrew L Croxford, Amit Awasthi, Valérie A Dardalhon, George Galileos, Patrick Vollmar, Gretta L Stritesky, Mark H Kaplan, Ari Waisman, Vijay K Kuchroo, Mohamed Oukka
The conditions leading to the induction of adaptive Foxp3(+) regulatory T cells (T-regs) from peripheral T cells in vivo are incompletely understood. Here, we show that unresponsiveness of T cells to IL-6 by T cell-selective deletion of gp130 or immunization of wild-type mice with antigen in incomplete Freund's adjuvant (IFA), which fails to induce IL-6, promotes the conversion of peripheral CD4(+) T cells into adaptive Foxp3(+) T-regs. Thus, both T cell-conditional gp130 knockout (KO) mice immunized with MOG35-55 in complete Freund's adjuvant (CFA) and wild-type mice immunized with MOG35-55 in IFA develop overwhelming antigen-specific T-reg responses and are protected from experimental autoimmune encephalomyelitis (EAE)...
November 25, 2008: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/12697742/immunoregulation-of-a-viral-model-of-multiple-sclerosis-using-the-synthetic-cannabinoid-r-win55-212
#8
J Ludovic Croxford, Stephen D Miller
Theiler murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) is a mouse model of chronic-progressive multiple sclerosis (MS) characterized by Th1-mediated CNS demyelination and spastic hindlimb paralysis. Existing MS therapies reduce relapse rates in 30% of relapsing-remitting MS patients, but are ineffective in chronic-progressive disease, and their effects on disability progression are unclear. Experimental studies demonstrate cannabinoids are useful for symptomatic treatment of spasticity and tremor in chronic-relapsing experimental autoimmune encephalomyelitis...
April 2003: Journal of Clinical Investigation
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