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240624s2024 xx |||||o 00| ||eng c |
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|a 10.1016/j.clim.2024.110287
|2 doi
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|a pubmed24n1479.xml
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|a DE-627
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|a eng
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| 100 |
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|a Damara, Aman
|e verfasserin
|4 aut
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| 245 |
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|a LL37/self-DNA complexes mediate monocyte reprogramming
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|c 2024
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|a Text
|b txt
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|a ƒaComputermedien
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|a ƒa Online-Ressource
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|a Date Completed 19.07.2024
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|a Date Revised 22.07.2024
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|a published: Print-Electronic
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|a Citation Status MEDLINE
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|a Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.
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|a LL37 alone and in complex with self-DNA triggers inflammatory responses in myeloid cells and plays a crucial role in the development of systemic autoimmune diseases, like psoriasis and systemic lupus erythematosus. We demonstrated that LL37/self-DNA complexes induce long-term metabolic and epigenetic changes in monocytes, enhancing their responsiveness to subsequent stimuli. Monocytes trained with LL37/self-DNA complexes and those derived from psoriatic patients exhibited heightened glycolytic and oxidative phosphorylation rates, elevated release of proinflammatory cytokines, and affected naïve CD4+ T cells. Additionally, KDM6A/B, a demethylase of lysine 27 on histone 3, was upregulated in psoriatic monocytes and monocytes treated with LL37/self-DNA complexes. Inhibition of KDM6A/B reversed the trained immune phenotype by reducing proinflammatory cytokine production, metabolic activity, and the induction of IL-17-producing T cells by LL37/self-DNA-treated monocytes. Our findings highlight the role of LL37/self-DNA-induced innate immune memory in psoriasis pathogenesis, uncovering its impact on monocyte and T cell dynamics
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|a Journal Article
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|a LL37/self-DNA complex
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|a Metabolic and epigenetic modifications
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|a Monocyte reprogramming
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|a Psoriasis
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|a Cathelicidins
|2 NLM
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|a DNA
|2 NLM
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|a 9007-49-2
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|a Antimicrobial Cationic Peptides
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|a Histone Demethylases
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|a EC 1.14.11.-
|2 NLM
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|a Cytokines
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|a Jumonji Domain-Containing Histone Demethylases
|2 NLM
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|a EC 1.14.11.-
|2 NLM
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|a Interleukin-17
|2 NLM
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|a Wegner, Joanna
|e verfasserin
|4 aut
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|a Trzeciak, Emily R
|e verfasserin
|4 aut
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| 700 |
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|a Kolb, Antonia
|e verfasserin
|4 aut
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|a Nastaranpour, Mahsa
|e verfasserin
|4 aut
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|a Khatri, Rahul
|e verfasserin
|4 aut
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|a Tuettenberg, Andrea
|e verfasserin
|4 aut
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| 700 |
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|a Kramer, Daniela
|e verfasserin
|4 aut
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| 700 |
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|a Grabbe, Stephan
|e verfasserin
|4 aut
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|a Shahneh, Fatemeh
|e verfasserin
|4 aut
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| 773 |
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|i Enthalten in
|t Clinical immunology (Orlando, Fla.)
|d 1999
|g 265(2024) vom: 21. Juli, Seite 110287
|w (DE-627)NLM098196855
|x 1521-7035
|7 nnns
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| 773 |
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|g volume:265
|g year:2024
|g day:21
|g month:07
|g pages:110287
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|u http://dx.doi.org/10.1016/j.clim.2024.110287
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