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在小鼠模型中,靶向Toll样受体2的全身应用人源化单克隆抗体对特应性皮炎样皮肤损伤的治疗潜力。

Therapeutic potential of a systemically applied humanized monoclonal antibody targeting Toll‑like receptor 2 in atopic‑dermatitis‑like skin lesions in a mouse model.

作者信息

Yeo Hyunjin, Jung Euitaek, Kim Tae Yoon, Shin Soon Young

机构信息

Department of Biological Sciences, Sanghuh College of Life Science, Konkuk University, Seoul 05029, Republic of Korea.

Cancer and Metabolism Institute, Konkuk University, Seoul 05029, Republic of Korea.

出版信息

Biomed Rep. 2024 Dec 30;22(3):41. doi: 10.3892/br.2024.1919. eCollection 2025 Mar.

DOI:10.3892/br.2024.1919
PMID:39781040
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11707563/
Abstract

Atopic dermatitis (AD) is a prevalent, persistent inflammatory skin disorder distinguished by pruritic and irritated skin. Toll-like receptors (TLRs) are specialized receptors that recognize specific patterns associated with pathogens and tissue damage, triggering an innate immune response that protects the host from invading pathogens. Previously, it was demonstrated that intradermal injection of the humanized anti-TLR2 monoclonal antibody (Ab) Tomaralimab effectively relieved AD-like skin inflammation in BALB/c mouse models exposed to house dust mite extracts. However, it remains unclear whether allergenic hapten-induced AD can be effectively treated with systemically administered TLR2-targeting Abs. In the present study, it was observed that administrating Tomaralimab through intravenous injection alleviated AD-like skin lesions in BALB/c mice challenged with topical application of 2,4-dinitrochlorobenzene by reducing the infiltration of inflammatory cells into skin lesions and preventing the creation of various inflammatory cytokines, including thymic stromal lymphopoietin, interleukin (IL)-4, IL-13, IL-17 and IL-31, which are associated with the pathogenesis of AD. These findings support the feasibility of using a humanized anti-TLR2 monoclonal Ab as systemic therapy for AD.

摘要

特应性皮炎(AD)是一种常见的、持续性炎症性皮肤病,其特征为皮肤瘙痒和发炎。Toll样受体(TLR)是一种特殊的受体,可识别与病原体和组织损伤相关的特定模式,触发先天性免疫反应,保护宿主免受入侵病原体的侵害。此前有研究表明,在暴露于屋尘螨提取物的BALB/c小鼠模型中,皮内注射人源化抗TLR2单克隆抗体(Ab)托马拉利单抗可有效缓解类AD皮肤炎症。然而,全身性给予靶向TLR2的抗体是否能有效治疗变应原性半抗原诱导的AD仍不清楚。在本研究中,观察到通过静脉注射给予托马拉利单抗,可减轻经局部应用2,4-二硝基氯苯攻击的BALB/c小鼠的类AD皮肤损伤,其机制为减少炎症细胞向皮肤损伤部位的浸润,并阻止包括胸腺基质淋巴细胞生成素、白细胞介素(IL)-4、IL-13、IL-17和IL-31在内的多种与AD发病机制相关的炎性细胞因子的产生。这些发现支持了使用人源化抗TLR2单克隆抗体作为AD全身治疗方法的可行性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4867/11707563/561a2344f3f0/br-22-03-01919-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4867/11707563/95175dd13c0a/br-22-03-01919-g00.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4867/11707563/e6db0ac72fd2/br-22-03-01919-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4867/11707563/fd78dae5a8af/br-22-03-01919-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4867/11707563/aa383c53ed77/br-22-03-01919-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4867/11707563/561a2344f3f0/br-22-03-01919-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4867/11707563/95175dd13c0a/br-22-03-01919-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4867/11707563/b017434e96a5/br-22-03-01919-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4867/11707563/e6db0ac72fd2/br-22-03-01919-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4867/11707563/fd78dae5a8af/br-22-03-01919-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4867/11707563/aa383c53ed77/br-22-03-01919-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4867/11707563/561a2344f3f0/br-22-03-01919-g05.jpg

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本文引用的文献

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Toll-like receptors: their roles in pathomechanisms of atopic dermatitis.Toll 样受体:在特应性皮炎发病机制中的作用。
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