International immunopharmacology最新文献_第5页

Recombinant allergen rBlo t 5 induces type 2 immune inflammation via Interleukin-10 and DDX58/IFIH1 Signaling pathways 重组过敏原rblot5通过白细胞介素-10和DDX58/IFIH1信号通路诱导2型免疫炎症

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology

Pub Date : 2026-01-31 DOI: 10.1016/j.intimp.2026.116282

Jinni Chen , Lingxiao Zhong , Kangdong Wang , Yaning Ren , Dongmei Zhou , Ying Zhou , Liuying Chen , Yuanfen Liao , Chuangli Hao , Yubao Cui

Blomia tropicalis is a clinically significant source of mite allergens, with Blo t 5 identified as a major component. This study aimed to produce recombinant Blo t 5 (rBlo t 5) and investigate its role in allergic immune responses. The rBlo t 5 protein (∼14 kDa) was successfully expressed in E. coli and purified with high purity. IgE-ELISA demonstrated specific IgE binding in 69% of serum samples from asthmatic children sensitized to B. tropicalis. Transcriptomic analysis of rBlo t 5-stimulated BEAS-2B bronchial epithelial cells revealed significant enrichment of genes associated with the interleukin-10 signaling and DDX58/IFIH1-mediated interferon-alpha/beta pathways. qPCR validation confirmed upregulation of key genes, including of CXCL1, CXCL2, CCL2, CCL5, IL1B, ICAM-1, RIG-I, IFIH1, IRF7, and ISG15. In a murine model of allergic airway inflammation, rBlo t 5 sensitization induced pronounced inflammatory cell infiltration, goblet cell hyperplasia, collagen deposition, and increased neutrophils in bronchoalveolar lavage fluid. Serum levels of allergen-specific IgE and IgG1 were elevated, accompanied by a Th2-skewed cytokine profile (increased IL-4 and IL-13, decreased IFN-γ and TGF-β). qPCR of lung tissues further confirmed upregulation of the same pathway-related genes.These findings indicate that rBlo t 5 elicits a type 2-polarized immune response initiated, in part, through the concurrent activation of the IL-10 and DDX58/IFIH1-interferon signaling axes in airway epithelium, providing new mechanistic insights into B. tropicalis-induced allergic inflammation.

热带布洛米亚螨是螨过敏原的临床重要来源，其中布洛5被确定为主要成分。本研究旨在制备重组Blo t5 （rBlo t5）并探讨其在变态反应免疫应答中的作用。在大肠杆菌中成功表达了rblot5蛋白（~ 14 kDa），并获得了高纯度的纯化。IgE- elisa结果显示，对热带芽孢杆菌敏感的哮喘儿童的血清样本中有69%的特异性IgE结合。rBlo t 5刺激的BEAS-2B支气管上皮细胞转录组学分析显示，与白细胞介素-10信号通路和DDX58/ ifih1介导的干扰素- α / β通路相关的基因显著富集。qPCR验证证实了CXCL1、CXCL2、CCL2、CCL5、IL1B、ICAM-1、RIG-I、IFIH1、IRF7、ISG15等关键基因的上调。在小鼠变应性气道炎症模型中，rblo5致敏诱导明显的炎症细胞浸润、杯状细胞增生、胶原沉积和支气管肺泡灌洗液中中性粒细胞增加。血清中过敏原特异性IgE和IgG1水平升高，并伴有th2偏斜的细胞因子谱（IL-4和IL-13升高，IFN-γ和TGF-β降低）。肺组织qPCR进一步证实了相同通路相关基因的上调。这些发现表明，rblot5引发了2型极化免疫应答，部分是通过同时激活气道上皮中IL-10和DDX58/ ifih1 -干扰素信号轴，为热带双球菌诱导的过敏性炎症提供了新的机制见解。

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引用次数: 0

Targeting DDX5 using FL118 suppresses mTOR signaling and tumorigenicity in JAK2V617F-driven myeloproliferative neoplasms. 在jak2v617f驱动的骨髓增生性肿瘤中，FL118靶向DDX5抑制mTOR信号和致瘤性。

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology

Pub Date : 2026-01-31 DOI: 10.1016/j.intimp.2026.116284

Kengo Takeda, Kenji Tago, Satoshi Ohta, Yosuke Nakazawa, Megumi Funakoshi-Tago

The constitutively active mutant of the tyrosine kinase Janus kinase 2 (JAK2V617F) is a major driver of myeloproliferative neoplasms (MPNs). We previously demonstrated that JAK2V617F activates the transcription factor signal transducer and activator of transcription 5 (STAT5), which upregulates the expression of the RNA helicase DDX5. DDX5 promotes activation of the mTOR pathway and is essential for the proliferation and tumorigenicity of JAK2V617F-positive hematopoietic cell models, even though its RNA helicase activity is dispensable for JAK2V617F-induced transformation. In the present study, we investigated the therapeutic potential of targeting DDX5 using FL118, a camptothecin (CPT) derivative known to induce the proteasomal degradation of DDX5. In Ba/F3 cells expressing JAK2V617F and the erythropoietin receptor (EpoR), as well as in human erythroleukemia (HEL) cells harboring JAK2V617F, FL118, but not CPT, successfully induced DDX5 degradation. Consist with this, FL118, but not CPT, suppressed mTOR pathway activation and triggered apoptosis in both Ba/F3 cells expressing JAK2V617F and EpoR and HEL cells. In a subcutaneous tumor model, in which Ba/F3 cells expressing JAK2V617F and EpoR were transplanted into nude mice, oral administration of FL118 significantly reduced tumor growth and hepatosplenomegaly. Collectively, these findings establish DDX5 as a promising therapeutic target in MPNs and underscore the potential of FL118 as a treatment strategy for JAK2V617F-driven disease.

酪氨酸激酶Janus激酶2 （JAK2V617F）的组成型活性突变体是骨髓增生性肿瘤（mpn）的主要驱动因素。我们之前证明JAK2V617F激活转录因子信号换能器和转录激活因子5 (STAT5)，从而上调RNA解旋酶DDX5的表达。DDX5促进mTOR通路的激活，对jak2v617f阳性造血细胞模型的增殖和致瘤性至关重要，尽管其RNA解旋酶活性对于jak2v617f诱导的转化是必不可少的。在本研究中，我们研究了使用FL118靶向DDX5的治疗潜力，FL118是一种喜树碱（CPT）衍生物，已知可诱导DDX5的蛋白酶体降解。在表达JAK2V617F和促红细胞生成素受体（EpoR）的Ba/F3细胞以及携带JAK2V617F的人红细胞白血病（HEL）细胞中，FL118，而不是CPT，成功地诱导了DDX5的降解。与此一致的是，FL118抑制了表达JAK2V617F的Ba/F3细胞、EpoR和HEL细胞的mTOR通路激活，并引发了细胞凋亡，而CPT没有。在皮下肿瘤模型中，将表达JAK2V617F和EpoR的Ba/F3细胞移植到裸鼠体内，口服FL118可显著降低肿瘤生长和肝脾增大。总的来说，这些发现确立了DDX5作为mpn的一个有希望的治疗靶点，并强调了FL118作为jak2v617f驱动疾病的治疗策略的潜力。

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引用次数: 0

Comment on: Asprosin mediates diabetes-associated depression via provoking the cascade of pyroptosis-neuroinflammation-kynurenine pathway disorder in the hippocampus 评论：Asprosin通过引发海马体中焦热-神经炎症-犬尿氨酸通路紊乱的级联反应介导糖尿病相关抑郁

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology

Pub Date : 2026-01-30 DOI: 10.1016/j.intimp.2026.116266

Li Jiamei , Li Keda

This letter to the editor comments on the study by Jiang et al. investigating the role of Asprosin in diabetes-associated depression. We acknowledge the novel finding that Asprosin mediates hippocampal dysfunction by triggering a cascade of “pyroptosis–neuroinflammation–kynurenine pathway” disruption. We further highlight several avenues for deeper exploration, including the brain-region specificity of Asprosin action, the specific cell types undergoing pyroptosis, and the direct mechanistic links within this pathway. Further investigation into these aspects may help translate this discovery into targeted therapeutic strategies.

这封致编辑的信评论了Jiang等人调查Asprosin在糖尿病相关抑郁症中的作用的研究。我们承认Asprosin通过触发“焦热-神经炎症-犬尿氨酸通路”的级联破坏介导海马功能障碍的新发现。我们进一步强调了几个深入探索的途径，包括Asprosin作用的脑区特异性，发生焦亡的特定细胞类型，以及这一途径中的直接机制联系。对这些方面的进一步研究可能有助于将这一发现转化为有针对性的治疗策略。

引用次数: 0

Immunological mechanisms and immunotherapeutic strategies for the maternal-fetal interface diseases during pregnancy 妊娠期母胎界面疾病的免疫机制及免疫治疗策略

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology

Pub Date : 2026-01-30 DOI: 10.1016/j.intimp.2026.116260

Shuo Zheng , Yulin Zhang , Yi Xing , Zhen Zhang , Yaqing Zhang , Liang Peng , Suya Chen , Yanli Zhang , Longquan Shao

The immune environment at the maternal-fetal interface is reliant on the precise regulation of various immune cells and their secreted cytokines, resulting in a coordinated balance of immune nutrition, immune defense, and immune tolerance to meet the needs of different stages of pregnancy. Disruption in the immunological microenvironment can lead to several pregnancy problems. In recent years, immunotherapy medications have made substantial advances in the treatment of maternal-fetal interface diseases during pregnancy. This paper provides a cellular and molecular review of the immunological mechanisms behind various common maternal-fetal interface diseases (preterm birth, recurring spontaneous abortion, preeclampsia, and fetal growth restriction). It offers a novel analysis of the mechanisms of action, application strategies, current research status, and future challenges for distinct immunotherapeutic agents from three separate perspectives: targeting different phases of inflammatory pathways, targeting particular immune cells at the maternal-fetal interface, and targeting specific autoantibodies associated with autoimmunity. The aim is to provide new insights for medication discovery, as well as precision diagnosis and treatment of pregnancy-related illnesses. These advancements will provide vital evidence for precision treatment of maternal-fetal interface diseases throughout pregnancy.

母胎界面的免疫环境依赖于各种免疫细胞及其分泌的细胞因子的精确调控，从而实现免疫营养、免疫防御和免疫耐受的协调平衡，以满足妊娠不同阶段的需要。免疫微环境的破坏会导致一些怀孕问题。近年来，免疫治疗药物在治疗妊娠期母胎界面疾病方面取得了实质性进展。本文从细胞和分子角度综述了各种常见母胎界面疾病（早产、反复自然流产、先兆子痫和胎儿生长受限）背后的免疫机制。它从三个不同的角度对不同的免疫治疗药物的作用机制、应用策略、目前的研究现状和未来的挑战进行了新的分析：针对炎症途径的不同阶段，针对母胎界面的特定免疫细胞，以及针对与自身免疫相关的特异性自身抗体。目的是为药物发现以及妊娠相关疾病的精确诊断和治疗提供新的见解。这些进展将为孕期母胎界面疾病的精准治疗提供重要依据。

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引用次数: 0

Corrigendum to "Unravelling the role of Interleukin-12 in Neuroinflammatory mechanisms: Pathogenic pathways linking Neuroinflammation to neuropsychiatric disorders" [Int. Immunopharmacol. 156 (2025) 114654]. “揭示白细胞介素-12在神经炎症机制中的作用：将神经炎症与神经精神疾病联系起来的致病途径”的勘误表[j]。免疫药理，156 (2025)114654 [j]。

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology

Pub Date : 2026-01-29 DOI: 10.1016/j.intimp.2026.116239

Rupali Chauhan, Maneesh Mohan, Ashi Mannan, Sushma Devi, Thakur Gurjeet Singh

引用次数: 0

Umbilical cord mesenchymal stem cell-derived exosomes delivered via a thermosensitive hydrogel ameliorate atopic dermatitis by mitigating keratinocyte mitochondrial damage through activating the Wnt/β-catenin pathway 通过热敏水凝胶递送的脐带间充质干细胞来源的外泌体通过激活Wnt/β-catenin通路减轻角质细胞线粒体损伤，改善特应性皮炎

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology

Pub Date : 2026-01-29 DOI: 10.1016/j.intimp.2026.116297

Xueping Zhao , Yue Zhang , Yue Dong , Chunrui Shi , Yi Wu

Atopic dermatitis (AD) is a chronic inflammatory skin condition with a high global prevalence and a multifactorial etiology. Its development is primarily attributed to defective skin barrier function, immune dysregulation, and oxidative stress-induced impairments in mitochondrial activity within keratinocytes. While mesenchymal stem cell-derived exosomes show promise as a cell-free therapy, their limited efficacy via traditional systemic administration is a major challenge. To address this, we developed a thermosensitive poloxamer hydrogel-based system for the local delivery of human umbilical cord mesenchymal stem cell-derived exosomes(hUCMSC-exo).

Our in vitro studies demonstrated that hUCMSC-exo were effectively internalized by HaCaT keratinocytes, significantly mitigating inflammatory responses, abnormal differentiation, and mitochondrial damage caused by IL-4/TNF-α. Through RNA-seq and mechanistic validation, we found that hUCMSC-exo exert their protective effects by activating the Wnt/β-catenin signaling pathway, which repairs the skin barrier and reduces oxidative stress. We successfully prepared and characterized the hydrogel, confirming its excellent biocompatibility and sustained-release properties. In a MC903-induced AD mouse model, local administration of the hUCMSC-exo hydrogel significantly improved AD-like symptoms and lowered serum IgE and Th2 cytokine levels. Compared to the topical steroid mometasone furoate, our formulation demonstrated comparable efficacy with a superior safety profile. Our study is the first to combine a thermosensitive hydrogel with hUCMSC-exo for local delivery, providing a safe and effective new therapeutic strategy for AD.

特应性皮炎（AD）是一种慢性炎症性皮肤病，具有高全球患病率和多因素病因。其发展主要归因于皮肤屏障功能缺陷、免疫失调和氧化应激诱导的角化细胞线粒体活性损伤。虽然间充质干细胞衍生的外泌体作为一种无细胞治疗有希望，但其通过传统系统给药的有限疗效是主要挑战。为了解决这个问题，我们开发了一种基于热敏波洛沙姆水凝胶的系统，用于人脐带间充质干细胞衍生的外泌体（hUCMSC-exo）的局部递送。我们的体外研究表明，hUCMSC-exo被HaCaT角质形成细胞有效内化，显著减轻炎症反应、异常分化和IL-4/TNF-α引起的线粒体损伤。通过RNA-seq和机制验证，我们发现hUCMSC-exo通过激活Wnt/β-catenin信号通路发挥保护作用，修复皮肤屏障，减少氧化应激。我们成功制备并表征了该水凝胶，证实了其良好的生物相容性和缓释性能。在mc903诱导的AD小鼠模型中，局部给药hUCMSC-exo水凝胶可显著改善AD样症状，降低血清IgE和Th2细胞因子水平。与外用类固醇糠酸莫米松相比，我们的配方显示出相当的疗效和优越的安全性。我们的研究首次将热敏水凝胶与hUCMSC-exo结合局部给药，为阿尔茨海默病提供了一种安全有效的新治疗策略。

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引用次数: 0

The circRNA0001707/miR-203a-3p/TLR4 regulatory axis drives macrophage polarization in enthesitis of newly diagnosed ankylosing spondylitis circRNA0001707/miR-203a-3p/TLR4调控轴在新诊断的强直性脊柱炎中驱动巨噬细胞极化

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology

Pub Date : 2026-01-29 DOI: 10.1016/j.intimp.2026.116262

Biqi Fu , Yao Zhou , Wei Long , Xinhua Yu , Qianbin Dai , Qing Luo , Rui Wu

Objectives

This study aimed to identify circular RNAs (circRNAs) associated enthesitis in patient with ankylosing spondylitis (AS) and to elucidate the underlying mechanism.

Methods

A multi-phase study was conducted. In the discovery phase, circRNA microarray analysis was performed on peripheral blood mononuclear cells (PBMCs) isolated from 3 AS patients and 3 healthy controls. Differentially expressed circRNAs were subsequently validated in two stages: an initial pilot verification followed by replication in an expanded cohort. The functional role of hsa_circ_0001707 in macrophage polarization was investigated in vitro using THP-1 cells.

Results

Microarray analysis and subsequent validation showed that AS patients exhibited significantly increased levels of hsa_circ_0001707 and reduced levels of hsa_circ_0075522 in PBMC compared to healthy controls. Stratified analysis revealed that hsa_circ_0001707 expression was significantly upregulated in AS patients with enthesitis compared to those without. Multivariate logistic regression analyses demonstrated that hsa_circ_0001707 was independently associated with enthesitis. In vitro, hsa_circ_0001707 overexpression promoted M1 polarization, increasing the secretion of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-23. Conversely, knockdown of hsa_circ_0001707 showed an opposite effect. Mechanistically, hsa_circ_0001707 acted as a molecular sponge for miR-203a-3p, thereby relieving repression of TLR4. Dual-luciferase assays confirmed direct interactions between miR-203a-3p and both hsa_circ_0001707 and TLR4.

Conclusion

This study identifies hsa_circ_0001707 as a novel biomarker for AS-associated enthesitis and suggests its role in promoting macrophage M1 polarization through the miR-203a-3p/TLR4 axis. These findings provide new insights into the pathogenesis of enthesitis and suggest potential therapeutic targets for AS.

目的：本研究旨在鉴定强直性脊柱炎（AS）患者中与疼痛相关的环状rna (circRNAs)，并阐明其潜在机制。方法采用多期研究方法。在发现阶段，对3名AS患者和3名健康对照者的外周血单个核细胞（PBMCs）进行了circRNA微阵列分析。差异表达的circrna随后分两个阶段进行验证：最初的试点验证，然后在扩大的队列中进行复制。利用THP-1细胞体外研究hsa_circ_0001707在巨噬细胞极化中的功能作用。结果微阵列分析和随后的验证表明，与健康对照相比，AS患者PBMC中hsa_circ_0075522水平显著升高，hsa_circ_0001707水平显著降低。分层分析显示，hsa_circ_0001707在AS患者中表达明显上调。多因素logistic回归分析显示hsa_circ_0001707与炎症独立相关。在体外，hsa_circ_0001707过表达促进M1极化，增加促炎细胞因子如TNF-α、IL-6、IL-23的分泌。相反，敲低hsa_circ_0001707则表现出相反的效果。机制上，hsa_circ_0001707作为miR-203a-3p的分子海绵，从而缓解TLR4的抑制。双荧光素酶测定证实了miR-203a-3p与hsa_circ_0001707和TLR4之间的直接相互作用。本研究发现hsa_circ_0001707是as相关炎症的一种新的生物标志物，并提示其通过miR-203a-3p/TLR4轴促进巨噬细胞M1极化的作用。这些发现为阑尾炎的发病机制提供了新的见解，并提出了AS的潜在治疗靶点。

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引用次数: 0

Unrevealing role of TLRs/NLRP receptors in halting Alzheimer's neuroinflammation: Current progress and existing therapies TLRs/NLRP受体在阻止阿尔茨海默病神经炎症中的作用尚不明确：目前的进展和现有的治疗方法

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology

Pub Date : 2026-01-29 DOI: 10.1016/j.intimp.2026.116285

Shubham Upadhayay

Alzheimer's disease (AD) is a multifactorial condition caused by genetic, environmental, metabolic, and immunological factors. These pathological alterations trigger oxidative stress, excitotoxicity, and neuroinflammation, leading to the degeneration of cholinergic neurons in the brain. Several studies have found that persistent neuroinflammation plays a key role in AD progression; still, no curative medicine is available to halt the disease progression. For this reason, exploring new target-based therapy is necessary for AD treatment. The current review aims to understand the inflammatory processes associated with the activation of toll-like receptors (TLRs) and Inflammasomes (NLRPs) in AD progression. Additionally, the impact of TLR and NLRP inhibitors on improving the condition of AD patients. As multiple studies have confirmed, TLR/NLRP activation stimulates the infiltration of inflammatory cytokines, which enhances AD severity. Similarly, various studies have shown that inhibition of the TLR/NLRP signaling axis reduces oxidative stress, inflammatory cytokines, and apoptosis, thereby demonstrating a neuroprotective effect. This review examines the roles of TLR and NLRP pathways in AD progression, focusing on preclinical and clinical evidence supporting the neuroprotective benefits of targeting these pathways in AD. This review extensively examined the molecular mechanisms of TLR/NLRP inhibitors, highlighting recent discoveries that could be used to initiate clinical trials in patients with Alzheimer's.

阿尔茨海默病（AD）是一种由遗传、环境、代谢和免疫因素引起的多因素疾病。这些病理改变引发氧化应激、兴奋性毒性和神经炎症，导致大脑胆碱能神经元的退化。一些研究发现，持续的神经炎症在阿尔茨海默病的进展中起着关键作用；然而，目前还没有有效的药物来阻止这种疾病的发展。因此，探索新的靶向治疗方法对阿尔茨海默病的治疗是必要的。本综述旨在了解AD进展中与toll样受体（TLRs）和炎性小体（nlrp）激活相关的炎症过程。此外，TLR和NLRP抑制剂对改善AD患者病情的影响。多项研究证实，TLR/NLRP激活刺激炎症细胞因子的浸润，从而加重AD的严重程度。同样，各种研究表明，抑制TLR/NLRP信号轴可减少氧化应激、炎症细胞因子和细胞凋亡，从而显示出神经保护作用。本综述探讨了TLR和NLRP通路在AD进展中的作用，重点关注支持靶向这些通路治疗AD的神经保护作用的临床前和临床证据。本综述广泛研究了TLR/NLRP抑制剂的分子机制，重点介绍了可用于阿尔茨海默病患者临床试验的最新发现。

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引用次数: 0

Corrigendum to "Sodium nitroprusside induces apoptosis of H9C2 cardiac muscle cells in a c-Jun N-terminal kinase-dependent manner" [Int. Immunopharmacol. 1 (2001) 967-978]. “硝普钠以c-Jun n末端激酶依赖的方式诱导H9C2心肌细胞凋亡”的更正[j]。免疫药理，1(2001)967-978。

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology

Pub Date : 2026-01-29 DOI: 10.1016/j.intimp.2026.116236

Han-Jung Chae, Hong-Seob So, Soo-Wan Chae, Ji-Sun Park, Myung-Sun Kim, Jay-Min Oh, Yeun-Tai Chung, Sei-Hoon Yang, Eun-Taik Jeong, Hyung-Min Kim, Rae-Kil Park, Hyung-Ryong Kim

引用次数: 0

Molecular and functional characterization of a novel Toll-like receptor 9-specific DNA aptamer with therapeutic potential 具有治疗潜力的新型toll样受体9特异性DNA适体的分子和功能表征

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology

Pub Date : 2026-01-28 DOI: 10.1016/j.intimp.2025.116134

Mariya Farooq , Bilal Ahmad , Abdul Waheed Khan , Hongjoon Choi , Moon Suk Kim , Sangdun Choi

Toll-like receptor 9 (TLR9) plays a pivotal role in immune activation through recognition of DNA motifs, making it a compelling target for immunomodulatory therapies. We employed an integrative approach combining computational docking, biophysical characterization, and functional assays to identify and characterize DNA aptamers targeting TLR9. From an initial pool of candidates, ATA2 (agonistic TLR9 aptamer) emerged as a potent TLR9 agonist, demonstrating dose-dependent induction of TNF-α production in macrophages with specificity confirmed by TLR9 antagonist inhibition. ATA2 also enhanced macrophage migration and activated dendritic cells but showed limited effects on B cells. Surface plasmon resonance revealed a moderate affinity interaction between ATA2 and TLR9 (KD = 2.94 μM). Structural analyses via HPLC indicated the presence of discrete conformational states and high thermal and chemical stability of ATA2. Molecular dynamics simulations further highlighted ATA2’s superior conformational stability and flexibility in binding TLR9 compared to another aptamer, ATA1, suggesting a versatile mode of interaction. Collectively, these findings elucidate the molecular basis of ATA2’s TLR9 agonistic activity and underscore its therapeutic potential as a stable and specific immunomodulatory agent.

toll样受体9 （TLR9）通过识别DNA基序在免疫激活中起着关键作用，使其成为免疫调节治疗的一个引人注目的靶点。我们采用了结合计算对接、生物物理表征和功能分析的综合方法来鉴定和表征靶向TLR9的DNA适体。从最初的候选药物中，ATA2（激动型TLR9适配体）作为一种有效的TLR9激动剂出现，显示出剂量依赖性诱导巨噬细胞中TNF-α的产生，其特异性被TLR9拮抗剂抑制证实。ATA2还能增强巨噬细胞迁移和激活树突状细胞，但对B细胞的作用有限。表面等离子体共振显示ATA2与TLR9之间存在中等亲和作用（KD = 2.94 μM）。高效液相色谱分析表明，ATA2具有离散构象，具有较高的热稳定性和化学稳定性。分子动力学模拟进一步表明，与另一种适体ATA1相比，ATA2在结合TLR9方面具有优越的构象稳定性和灵活性，这表明ATA2具有多种相互作用模式。总的来说，这些发现阐明了ATA2的TLR9激动活性的分子基础，并强调了其作为稳定和特异性免疫调节剂的治疗潜力。

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引用次数: 0