系统性炎症诱导的脂肪组织重塑通过表观遗传和免疫代谢失调驱动肥胖的银屑病恶化。

IF 13.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Theranostics Pub Date : 2025-07-28 eCollection Date: 2025-01-01 DOI:10.7150/thno.116796
Jinsun Jang, Mijoo Ahn, Jiyeong Jeong, Eun-Hui Lee, Ok-Hee Kim, Seul-A Joo, Seung Eun Baek, Han-Joo Maeng, Yun Hak Kim, In-Sun Hong, Byung-Chul Oh, Ik Soo Kim, Hee Joo Kim, YunJae Jung
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引用次数: 0

摘要

理由:脂肪组织稳态的破坏越来越被认为是肥胖背景下银屑病炎症的关键驱动因素。然而,将脂肪功能障碍与疾病严重程度联系起来的机制仍然不完全清楚。方法:采用吡喹莫特外用或皮肤注射IL-23诱导的肥胖小鼠银屑病模型。来自这些小鼠的炎症谱与靶向RNA和染色质可及性的多组单核测序相结合,以研究脂肪组织的遗传和表观遗传改变。结果:肥胖小鼠在咪喹莫特治疗后银屑病皮炎明显加重,伴有全身炎症反应增加和脂肪量显著减少。组织学和分子分析显示,与瘦小鼠相比,肥胖小鼠的单核巨噬细胞广泛浸润到性腺周围脂肪组织,促炎基因表达增加,细胞死亡相关分子上调。相比之下,IL-23注射在瘦小鼠和肥胖小鼠中都引起了类似的皮肤炎症,而没有引起脂肪组织损失或全身炎症。吡喹莫特治疗肥胖小鼠的多组学分析揭示了促进脂肪酸消耗的脂肪细胞的遗传和表观遗传变化。此外,在巨噬细胞群体中观察到一种转变——从il -23处理小鼠中具有活跃细胞间通讯的脂质相关亚群,到咪喹莫特处理小鼠中具有单核细胞积聚的紊乱的巨噬细胞室。结论:这些研究结果表明,肥胖使脂肪组织对体内平衡破坏敏感,使其成为一个关键的免疫代谢界面,在系统性炎症提示下驱动银屑病恶化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Systemic inflammation-induced adipose tissue remodeling drives psoriasis exacerbation in obesity through epigenetic and immunometabolic dysregulation.

Rationale: Disruption of adipose tissue homeostasis is increasingly recognized as a key driver of psoriatic inflammation in the context of obesity. However, the mechanisms linking adipose dysfunction to disease severity remain incompletely understood. Methods: We employed an obese mouse model of psoriasis induced by topical imiquimod application or dermal IL-23 injection. Inflammatory profiling from these mice was integrated with multi-omic single-nucleus sequencing targeting RNA and chromatin accessibility to investigate genetic and epigenetic alterations in adipose tissue. Results: Obese mice developed markedly aggravated psoriatic dermatitis following imiquimod treatment, accompanied by increased systemic inflammatory responses and a significant reduction in fat mass. Histological and molecular analyses revealed extensive monocyte-macrophage infiltration into perigonadal adipose tissue, increased expression of pro-inflammatory genes, and upregulation of cell death-associated molecules in obese mice relative to lean counterparts. In contrast, IL-23 injection elicited comparable skin inflammation in both lean and obese mice without inducing adipose tissue loss or systemic inflammation. Multi-omic profiling of imiquimod-treated obese mice revealed genetic and epigenetic changes in adipocytes that promote fatty acid consumption. Furthermore, a shift was observed in macrophage populations-from a lipid-associated subset with active intercellular communication in IL-23-treated mice to disorganized macrophage compartments with monocyte accumulation in imiquimod-treated mice. Conclusions: These findings suggest that obesity sensitizes adipose tissue to homeostatic disruption, establishing it as a critical immunometabolic interface that drives psoriasis exacerbation in response to systemic inflammatory cues.

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来源期刊
Theranostics
Theranostics MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
25.40
自引率
1.60%
发文量
433
审稿时长
1 months
期刊介绍: Theranostics serves as a pivotal platform for the exchange of clinical and scientific insights within the diagnostic and therapeutic molecular and nanomedicine community, along with allied professions engaged in integrating molecular imaging and therapy. As a multidisciplinary journal, Theranostics showcases innovative research articles spanning fields such as in vitro diagnostics and prognostics, in vivo molecular imaging, molecular therapeutics, image-guided therapy, biosensor technology, nanobiosensors, bioelectronics, system biology, translational medicine, point-of-care applications, and personalized medicine. Encouraging a broad spectrum of biomedical research with potential theranostic applications, the journal rigorously peer-reviews primary research, alongside publishing reviews, news, and commentary that aim to bridge the gap between the laboratory, clinic, and biotechnology industries.
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