LL37/self-DNA complexes mediate monocyte reprogramming

LL37/self-DNA complexes mediate monocyte reprogramming

Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 265(2024) vom: 21. Juli, Seite 110287
1. Verfasser: Damara, Aman (VerfasserIn)
Weitere Verfasser: Wegner, Joanna, Trzeciak, Emily R, Kolb, Antonia, Nastaranpour, Mahsa, Khatri, Rahul, Tuettenberg, Andrea, Kramer, Daniela, Grabbe, Stephan, Shahneh, Fatemeh
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2024
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article LL37/self-DNA complex Metabolic and epigenetic modifications Monocyte reprogramming Psoriasis Cathelicidins DNA 9007-49-2 Antimicrobial Cationic Peptides Histone Demethylases mehr... EC 1.14.11.- Cytokines Jumonji Domain-Containing Histone Demethylases Interleukin-17
Beschreibung
Zusammenfassung:Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.
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
Beschreibung:Date Completed 19.07.2024
Date Revised 22.07.2024
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2024.110287