CLINICAL AND EXPERIMENTAL ALLERGY
·
2025
·
IF 5.2
Yanran Huang,Zhaofeng Xu,Yan Yan,Chunbo Li,Jieying Yan,Yi Wei,Jian Li,Luo Zhang,Nan Zhang,Claus Bachert,Weiping Wen
Background Immunoglobulin overproduction was observed in type 2 chronic rhinosinusitis with nasal polyps (CRSwNP). Endoplasmic reticulum (ER) stress is linked to aggregation in various inflammatory diseases, yet its presence and extent in nasal polyps remain to be elucidated. Objective To assess the impact of B-cell ER stress on local immunoglobulin production in CRSwNP and investigate its correlation with disease severity. Methods Single-cell mapped transcriptional profiles at cellular resolution. Electron microscopy revealed ultrastructural features, complemented by immunohistochemistry/immunofluorescence mapping marker localisation. Western blotting quantified protein expression, with QuantiGene Plex and Luminex enabling multiplex cytokine analysis. Bulk RNA sequencing and targeted protein expression validation in ex vivo experiments confirmed critical findings. Results HSPA5 and HSP90B1 were found to be two major elevated ER stress markers in type 2 CRSwNP, compared to the control nasal tissue, and their expression correlated with the expression of IGHE and type 2 inflammatory markers. In CRSwNP, the ER stress signature score and increased marker expression predominantly originated from B and plasma cells. Electron microscopy revealed dilated ER and enlarged lumen in sorted B cells from nasal polyps. MZB1 exhibited co-localisation with plasma cells and mature B cells. Immunofluorescence staining demonstrated that MZB1 co-localised with HSPA5 and HSP90B1. In vitro, stimulation with MZB1 upregulated mRNA expression of ER stress markers and IgE. Increased IGHE expression was detected in response to ER stress induced in vitro. Finally, anti-IgE treatment inhibited the expression of ER stress-related genes. Conclusion ER stress markers were significantly upregulated in CRSwNP. Specifically, ER stress levels were significantly elevated in B cells of CRSwNP compared to controls. In type 2 CRSwNP, B-cell ER stress may play a role in promoting local IgE production. Graphical The ER stress burden was significantly upregulated in type 2 CRSwNP tissues compared to both healthy controls and non-type 2 polyp tissues. This elevated stress was linked to more severe type 2 inflammation and increased local IgE production. In vitro studies of B cells derived from nasal polyp tissues demonstrated that MZB1 upregulated endoplasmic reticulum stress, which was associated with enhanced IgE level. Furthermore, in vivo treatment with Omalizumab reduced endoplasmic reticulum stress levels. ER, endoplasmic reticulum; HC, healthy controls; CRSwNP, chronic rhinosinusitis with nasal polyps; MZB1, Marginal Zone B1 protein.
研究领域:
耳鼻喉科学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Shukun Zhao,Qiong Jiang,Ling Yu,Quan Liu,Zi Chen,Danting Zhan,Shuyu Chen,Yuqiong Yang,Jiacheng Zhong,Bingxin Guo,Fei Shi,Rongchang Chen,Lingwei Wang,Lang Rao,Junxia Zheng,Qian-Fang Meng,Shanze Chen
Eosinophilic asthma is a chronic inflammatory disease driven by Type 2 immune cells and cytokines. While cytokine-based immunotherapies have shown promising efficacy in asthma treatment, current approaches often fail to simultaneously target multiple cytokines. In this study, we present nanodecoys derived from the cellular membranes of M2 macrophages, which exhibit a high density of cytokine receptors, enabling efficient sequestration of multiple Type 2 cytokines. This mechanism significantly alleviates OVA-induced eosinophilic asthma inflammation in mice. To enhance therapeutic efficacy, D-mannose glycans, a potential immunoregulatory molecule for asthma, were modified onto the surface of the nanovesicles. This modification facilitates the phagocytic clearance of absorbed cytokines by targeting the mannose receptor (CD206). Consequently, the mannose-modified nanovesicles exhibit synergistic immunosuppressive effects on asthmatic inflammation by inhibiting M2 macrophage polarization, CD4+ T cell Th2 polarization, and eosinophil activation, as revealed by single-cell RNA sequencing and in vitro analyses. In summary, this study presents a safe and effective nanotechnology-based immunotherapy for asthma and potentially other Type 2 inflammatory diseases.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-15
·
IF 16.6
Yang Yang,Chu Chenyu,Liu Li,Wang Chenbing,Hu Chen,Rung Shengan,Man Yi,Qu Yili
Skin scarring devoid of dermal appendages after severe trauma has unfavorable effects on aesthetic and physiological functions. Here we present a method for large-area wound regeneration using biodegradable aligned extracellular matrix scaffolds. We show that the implantation of these scaffolds accelerates wound coverage and enhances hair follicle neogenesis. We perform multimodal analysis, in combination with single-cell RNA sequencing and spatial transcriptomics, to explore the immune responses around biomaterials, highlighting the potential role of regulatory T cells in mitigating tissue fibrous by suppressing excessive type 2 inflammation. We find that immunodeficient mice lacking mature T lymphocytes show the typical characteristic of tissue fibrous driven by type 2 macrophage inflammation, validating the potential therapeutic effect of the adaptive immune system activated by biomaterials. These findings contribute to our understanding of the coordination of immune systems in wound regeneration and facilitate the design of immunoregulatory biomaterials in the future.
研究领域:
免疫学
·
生物材料科学
·
组织工程
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2024
·
IF 5.7
Long Zhou,Yingxin Yang,Tingjie Li,Yafang Zhao,Jinye Yuan,Chenxin He,Yan Huang,Jinyu Ma,Yue Zhang,Fang Lu,Jiaze Wu,Zijian Li,Hui Kong,Yan Zhao,Huihua Qu
Background: Allergic rhinitis (AR) affects up to 40% of the population, leading to significant healthcare expenditures. Current mainstream treatments, while effective, can lead to side effects and do not address the underlying immunological imbalances. Zingiberis Rhizoma Carbonisatum (ZRC), the partially charred product of Zingiberis Rhizoma (ZR), has been widely used clinically in China since ancient times to treat respiratory disorders.Methods: Inspired by the similarity between high-temperature pyrolysis and carbonization processing of herbal medicine, ZRC derived CDs (ZRC-CDs) were extracted and purified through several procedures. Then, the physicochemical characteristics of CDs were delineated through a suite of characterization methods. Moreover, our investigation zeroed in on elucidating the ameliorative impacts of CDs on ovalbumin-induced rat models alongside their underlying mechanisms.Results: ZRC-CDs with particle sizes ranging from 1.0 to 3.5 nm and rich surface functional groups. Additionally, we observed that ZRC-CDs significantly attenuated nasal symptoms and pathological damage in ovalbumin-induced AR rats, and modulated lipid metabolism and type 2 inflammatory responses. They also inhibit PI3K/AKT and JAK/STAT pathways, which are associated with metabolism and inflammation. Importantly, ZRC-CDs demonstrated high biocompatibility, underscoring their potential as a novel therapeutic agent.Conclusion: ZRC-CDs offer a promising alternative for AR treatment and could help facilitate broader clinical use of the ZRC. In addition, the exploration of the inherent bioactivity of CDs can help to broaden their biological applications.
研究领域:
药理学
·
免疫学
·
纳米技术
·
中医药
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）