학술논문
LL37/self-DNA complexes mediate monocyte reprogramming.
Document Type
Academic Journal
Author
Damara A; Department of Dermatology, University Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany.; Wegner J; Department of Dermatology, University Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany.; Trzeciak ER; Department of Dermatology, University Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany.; Kolb A; Department of Dermatology, University Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany.; Nastaranpour M; Department of Dermatology, University Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany.; Khatri R; Department of Dermatology, University Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany.; Tuettenberg A; Department of Dermatology, University Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany; Research Center for Immunotherapy, University Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany.; Kramer D; Department of Dermatology, University Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany; Research Center for Immunotherapy, University Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany.; Grabbe S; Department of Dermatology, University Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany; Research Center for Immunotherapy, University Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany.; Shahneh F; Department of Dermatology, University Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany; Research Center for Immunotherapy, University Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany. Electronic address: Fatemeh.Zare-Shahneh@unimedizin-mainz.de.
Source
Publisher: Academic Press Country of Publication: United States NLM ID: 100883537 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1521-7035 (Electronic) Linking ISSN: 15216616 NLM ISO Abbreviation: Clin Immunol Subsets: MEDLINE
Subject
Language
English
Abstract
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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)