Journal of Asthma and Allergy
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2022
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IF 3.027
Yang Sun,Tiancong Liu,Weiliang Bai
Purpose This work aimed to investigate the effects of MAF bZIP transcription factor B (MAFB) on the progression of allergic rhinitis (AR). Patients and Methods Nasal mucosa was isolated from AR patients and healthy individuals from Shengjing Hospital of China Medical University. The experimental procedures were approved by the Medical Ethics Committee of Shengjing Hospital of China Medical University (2019PS341K) in accordance with the Declaration of Helsinki. Informed consents were signed by participants or a parent/legal guardian of the participants under 18 years old of age. Then, an AR mouse model with MAFB overexpression was established with 25 μg ovalbumin (OVA) sensitization on day 0, 7, 14, followed by an injection with 1×10 7 TU/mL lentivirus MAFB on day 19 and a nasal challenge with 500 μg OVA from day 21 to 27. Results The results revealed that MAFB was down-regulated in the nasal mucosa of AR patients. The up-regulation of MAFB protected the AR mice against the OVA-induced allergic symptoms (sneezing and nasal rubbing) by alleviating the OVA-induced epithelial thicknesses, goblet cell hyperplasia, and inflammation including the eosinophil and mast cell infiltration. Moreover, MAFB facilitated the T helper (Th) 1 response and inhibited the Th2 and Th17 responses by the down-regulation of T-box transcription factor 21 and the up-regulation of GATA binding protein-3 as well as retinoid-related orphan receptor-γt in the splenocytes of AR mice. MAFB was found to repress the differentiation of naive CD4 + T cells into Th2 cells. Subsequently, MAFB overexpression reversed the OVA-induced enhancement of epithelial permeability, downregulation of tight junctions, and upregulation of cadherin-26, indicating the protective role of MAFB on epithelial barrier integrity. Conclusion MAFB protected against OVA-induced AR via the alleviation of inflammation by restoring the Th1/Th2/Th17 imbalance and epithelial barrier dysfunction.
研究领域:
免疫学
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分子生物学
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转化医学
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DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2018
·Vol. 18
·期 1
·622-626
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IF 1.922
Qin Zhu,Peifen Zheng,Jianying Zhou,Xinyu Chen,Yuliang Feng,Weifeng Wang,Feng Zhou,Qiaona He
Ulcerative colitis (UC) is a chronic, idiopathic, inflammatory bowel disease of the colon. T cell responses have been associated with the pathology of UC. Andrographis paniculata (AP) extract has been previously reported as an effective treatment of UC. The present study aimed to explore the effects of andrographolide, the primary active component of AP, on the T cell responses of patients with UC. Peripheral blood mononuclear cells (PBMCs) were isolated from patients with UC and treated with various concentrations of andrographolide (0, 10, 20 and 30 µg/ml). Andrographolide decreased interferon γ, interleukin (IL)‑23 and IL‑17A, however it increased IL‑4 in a dose‑dependent manner, as indicated by ELISA assay. Andrographolide treatment resulted in a decreased percentage of T helper (Th)1 and Th17 cells and an increased proportion of Th2 cells, as demonstrated by flow cytometry analysis. T‑bet (a Th1‑specific transcription factor) and RAR‑related orphan receptor γt (key transcription factor of Th17 cells) expression was decreased, but GATA‑3 (Th2 lineage‑specific transcription factor) expression was increased following andrographolide treatment as indicated by western blot analysis. These results demonstrated the inhibitory effects on Th1/Th17 responses and the promoting effects on Th2 responses of andrographolide. Experiments on IL‑23‑treated PBMCs from healthy donors revealed similar effects of andrographolide on Th1/Th2/Th17 responses. In summary, these results suggest that andrographolide may be an effective candidate for the treatment of IL‑23‑mediated diseases.
研究领域:
免疫学
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药理学
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炎症性肠病
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DOI
PubMed
高影响因子
SOUTH AFRICAN JOURNAL OF BOTANY
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2026
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IF 3.1
Xiao-Gang Sun,Bin-He Yang,Xiao-Lin Yang,Fei Li,Li-Jun Hao
Background This study combined network pharmacology with experimental validation to assess the therapeutic potential of Polygonum capitatum against atopic dermatitis (AD), elucidating its multi-target mechanisms and antibacterial/antipyretic properties in AD-related complications. Methods Potential targets and pathways were predicted using network pharmacology. HPLC was employed to quantify gallic acid, protocatechuic acid, rutin, quercitrin, and quercetin. Antimicrobial activity was evaluated via agar diffusion assays against Escherichia coli and Staphylococcus aureus . Anti-inflammatory activity was assessed by measuring ROS and NO levels in lipopolysaccharide-induced zebrafish. Models of AD were analyzed through SCORAD scoring, histopathological examination, and quantification of cytokines including LTB4 and Th1/Th2 markers. Thermoregulatory responses and serum inflammatory markers were examined using yeast-induced fever models. Finally, molecular docking was performed to validate interactions between the core components and their potential targets. Results Network analysis revealed 88 common targets and identified TNF, JAK2, and PTGS2 as core targets, enriched in immune-inflammatory pathways. Significant levels of the five compounds were detected, with flavonoid content being ethanol-dependent. The 95% ethanol extract inhibited bacterial growth and ameliorated AD-like pathology, including immune dysregulation. Both extracts reduced ROS/NO and fever responses, attenuating pro-inflammatory cytokines. Molecular docking confirmed stable binding between quercetin/rutin and core targets. Conclusion P. capitatum exerts multimodal anti-AD effects through multi-component, multi-target mechanisms involving antimicrobial, immunomodulatory, and antipyretic activities, attributable to its phenolic and flavonoid constituents.
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高影响因子
JOURNAL OF BIOLOGICAL CHEMISTRY
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2026
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IF 4.1
Dongsheng Xing,Hongwei Cao,Yan Yang,Shengyang Liu,Hanbing Yu,Zhenyu Liu,Kunrong Wang,Xin Wei,Aihui Yan
Tristetraprolin (TTP), which encodes an RNA-binding protein, was identified as a biomarker in three types of IgE-driven allergic tissues. Remarkably, in the nasal mucosa of the ragweed pollen-induced AR mouse model, TTP mRNA levels were increased approximately threefold. TTP overexpression in AR mice alleviated nasal inflammation and epithelial barrier damage, accompanied by reduced frequency of nasal spray and nasal friction, eosinophils/neutrophils/macrophages/goblet cells infiltration, and Th2 cytokines interleukin (IL)-4, IL-5, and IL-13 secretion. The impact of TTP on the activation and differentiation of Th2 cells was assessed by utilizing naïve CD4 T cells isolated from mice. We found that TTP significantly suppressed Th2 activation and differentiation, as evidenced by the decreased levels of cytokines and the percentage of Th2. Transcriptomic profiling of CD4+ T cells (with/without TTP overexpression) was analyzed, and 14 down-regulated genes containing AU-rich elements (AREs) were obtained. The study concentrated on downregulated E3 ubiquitin ligase tripartite motif 18 (TRIM18) in TTP-overexpressed CD4+ T cells. Specifically, TTP protein bound to the ARE located at positions +3640 to +3644 (5’-UAUUU-3’) within the 3’UTR of mouse TRIM18, and this interaction reduces TRIM18 mRNA stability, a process that depends on the active-site residue Cys-139 within the second CCCH-type zinc finger motif of TTP. TRIM18 overexpression weakened the effects in CD4+ T cells induced by TTP overexpression. Collectively, TTP suppresses Th2 activation and differentiation in AR by modulating TRIM18 mRNA stability, highlighting their interaction as a critical pathway in allergic inflammation.
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PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2026
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IF 5.6
Boyu Cai,Zhao Wang,Maoxiang Xu,Jiaojiao Li,Danni Li,Fei Tan
MSC-sEV attenuate eosinophilic nasal inflammation and mucosal remodeling in vivo. • MSC-sEV restore splenic Th1 and reduce Th17 cells, rebalancing T-helper responses. • MSC-sEV attenuate EMT-like changes and epithelial barrier dysfunction in ECRS. • RNA-seq and immunoblot link MSC-sEV effects to IL-17, TNF and JAK-STAT signaling. • Intranasal MSC-sEV offers a cell-free nanotherapy for refractory ECRS. Eosinophilic chronic rhinosinusitis (ECRS) is a refractory subtype characterized by dominant Th2 inflammation and progressive tissue remodeling, with high postoperative recurrence and limited efficacy of current biological agents. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEV) represent a promising cell-free nanotherapeutic approach, yet their efficacy in ECRS remains poorly studied. This study investigated the therapeutic efficacy of intranasal MSC-sEV against Th2/Th17 immune dysregulation and mucosal remodeling in a papain-induced ECRS model. Intranasal administration of MSC-sEV during the challenge phase significantly alleviated clinical symptoms and attenuated key pathological features, including epithelial hyperplasia, goblet cell hyperplasia, excessive mucus secretion and mucosal eosinophil infiltration, the latter confirmed by direct eosinophil quantification on H& E -stained sections. Immunohistochemistry showed that MSC-sEV attenuated airway remodeling by downregulating markers such as FXIII-A and CLCA1 while partially restoring E-cadherin levels, indicating attenuation of EMT-like changes. Flow cytometry of splenic lymphocytes revealed that MSC-sEV partially restored the disturbed systemic Th1/Th2/Th17 balance, with a more evident effect on the Th17-associated response, and immunohistochemistry for GATA3, IL-17 A and TNF-α confirmed concordant changes in the nasal mucosa. Transcriptomic analysis showed that these therapeutic effects were associated with downregulation of eosinophil-recruitment chemokines ( Ccl11 , Ccl24 ) and with reduced enrichment of IL-17, TNF and JAK-STAT signaling—corroborated at the protein level by decreased phosphorylation of STAT3 and NF-κB p65 and by RT-qPCR confirmation of nine key transcripts. Collectively, this study identifies MSC-sEV as an effective cell-free strategy that attenuates the development of ECRS by partially restoring immune homeostasis and attenuating epithelial remodeling. Download: Download high-res image (172KB) Download: Download full-size image
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高影响因子
Journal of Innate Immunity
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2020
·Vol. 13
·期 1
·38-48
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IF 4.932
Wang Tianyue,Zhou Qianlan,Shang Yunxiao
Children exposed to common aeroallergens may develop asthma that progresses into adulthood. Inflammation regulated by T helper 2 (Th2) cells, a specific subpopulation of CD4+ T lymphocytes, is involved in asthmatic injury. Herein, our microarray data indicated that microRNA-451a-5p (miRNA-451a) expression decreased by 4.6-fold and ETS proto-oncogene 1 (ETS1) increased by 2.2-fold in the peripheral blood lymphocytes isolated from asthmatic children (n = 4) as compared to control individuals (n = 4). The negative correlation between miRNA-451a and ETS1 was further validated in 40 CD4+ T cell samples (10 healthy vs. 30 asthmatic samples). In vitro, naïve CD4+ T cells isolated from control individuals were cultured under Th2 cell polarizing condition. miRNA-451a expression decreased while ETS1 increased in CD4+ T cells in the setting of Th2 cell polarization. Moreover, miRNA-451a knockdown enhanced Th2 cell polarization – cells positive for both GATA3 (GATA binding protein 3, a Th2-transcription factor) and CD4 increased, and the generation of Th2 cell cytokines, interleukin (IL)5 and IL13, increased. In contrast, miRNA-451a overexpression inhibited Th2 cell differentiation. Interestingly, dual-Luciferase assay proved ETS1 as a novel target of miRNA-451a. Moreover, enforced expression of ETS1 partially restored miRNA-451a-induced inhibition of IL5 and IL13, and increased the GATA3+CD4+ cell population. Collectively, our work demonstrates that downregulation of miRNA-451a upregulates ETS1 expression in CD4+ T cells, which may contribute to Th2 cell differentiation in pediatric asthma
研究领域:
免疫学
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分子生物学
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儿科
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DOI
PubMed
高影响因子
JOURNAL OF ASTHMA
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2015
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IF 1.802
Xingliang Zhang,Wenqing Zhong,Qingqi Meng,Qianwen Lin,Chao Fang,Xiulan Huang,Chengyan Li,Yuge Huang,Jianxin Tan
Objective: Epidemiological studies have shown that elevated concentrations of ambient particulate matter (aerodynamic diameter ≤2.5 μm; PM2.5) correlates with increased incidence of asthma. The aim of this study was to determine whether PM2.5 participates in the exacerbation of asthma. Methods: Effects of 1, 10 and 100 μg PM2.5 instilled intratracheally in ovalbumin (OVA)-sensitized or asthmatic mice were compared. Results: PM2.5 exposure in the OVA-sensitized and especially asthmatic groups increased Mch responsiveness in a dose-dependent manner. In OVA-sensitized groups, exposure to 1 μg of PM2.5 caused no detectable lung inflammation, while 10 and 100 μg of PM2.5 resulted in a slightly increased trend in numbers of neutrophils and macrophages. Compared with the asthmatic control group, both 10 and 100 μg of PM2.5 provoked a significant increase in eosnophils and neutrophils whereas only 100 μg of PM2.5 noticeably enhanced lymphocytes. In asthmatic groups, administration of 100 μg of PM2.5 greatly increased levels of the pro-inflammatory cytokine TNF-α and Th2-related cytokines IL-4 and IL-10 in bronchoalveolar lavage fluid, but it decreased Th1-related INF-γ. In addition, 10 and 100 μg of PM2.5 exacerbated inflammatory infiltration, goblet cell metaplasia and lung ultrastructure lesions in asthmatic mice. Conclusions: Our results suggested that acute exposure of PM2.5 could synergize with allergens in the subsequent challenge to aggravate the severity of asthma in sensitized mice, possibly by promoting a Th2-biased immune response.
研究领域:
环境卫生
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免疫学
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呼吸系统疾病
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DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
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2026
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IF 6.5
Ping Lv,Dandan Li,Wei Song,Jizhe Wang
Allergic rhinitis (AR) is a chronic inflammatory disorder characterized by type 2 T helper (Th2) cell-dominant immune responses. NEDD4 like E3 ubiquitin protein ligase (NEDD4L) plays a role in regulating T cell activation and Th cell differentiation. Dipeptidyl peptidase 4 (DPP4) is involved in Th2 inflammatory responses in AR. In this study, NEDD4L was found to be downregulated in peripheral blood CD4 + –enriched T cells from AR patients. In a BALB/c mouse model of AR, established by intraperitoneal sensitization with 25 μg ovalbumin (OVA) followed by intranasal challenge with 500 μg OVA, NEDD4L expression was also reduced in splenic T cells enriched in CD4 + populations. T cell-specific overexpression of NEDD4L, achieved via tail vein injection of lentivirus carrying the CD3δ promoter, significantly alleviated AR symptoms, as shown by reduced sneezing and nose-wiping frequency, and decreased serum levels of OVA-specific immunoglobulin E (IgE) and histamine. Moreover, NEDD4L overexpression attenuated nasal mucosal thickening, inflammatory cell infiltration, and goblet cell hyperplasia. In vitro , lentiviral-mediated NEDD4L overexpression in T cells, enriched in CD4 + populations, is associated with suppression of Th2-linked inflammation, as indicated by decreased GATA-binding protein 3 (GATA-3) and JunB proto-oncogene (JunB) protein levels, reduced secretion of Th2 cytokines, and a lower proportion of CD4 + IL-4 + cells. Mechanistically, NEDD4L ubiquitinates DPP4 at the K583 site to promote its degradation, and DPP4 overexpression reversed the anti-inflammatory effects of NEDD4L. Collectively, NEDD4L is consistent with acting as a negative regulator of Th2-linked inflammation, potentially via ubiquitination-mediated degradation of DPP4.
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
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IF 6.2
Zhencong Yang,Xue Feng,Philippe Madjirebaye,Yuting Fan,Li Yan,Zhoujin Xu,Xuli Wu
Although sodium nitrite (SN) is broadly used as a food preservative, its immunomodulatory effects on food allergy pathogenesis remain poorly understood. This study examined how subchronic SN exposure influences dendritic cell (DC)-mediated sensitization and T-cell polarization in an Ovalbumin (OVA)-induced mouse food allergy (FA) model. Our findings reveal that SN exacerbated allergic responses manifested by increased clinical symptoms, reduced weight gain, and elevated serum histamine, MCP-1, and IgE levels compared to those of OVA-sensitization alone. Mechanistically, SN promoted Th2 polarization through T-bet/GATA3 imbalance, Treg suppression, and enhanced DC activation. In vitro studies have demonstrated augmented antigen uptake by SN, MHC II expression, and selectively activated MAPK (p-JNK/ERK1/2) and STAT6 pathways, amplifying Th2 cytokine production and IgE class switching. These findings indicate that SN might disrupt immune homeostasis through coordinated modulation of DC function, Th2 polarization, and regulatory mechanisms, which highlights the potential of SN to exacerbate FA via multiple immunomodulatory pathways.
研究领域:
免疫学
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过敏与免疫学
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分子免疫学
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营养免疫学
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黏膜免疫学
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信号转导
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食品毒理学
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产品关联
DOI
PubMed
高影响因子
ACS Omega
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2023
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IF 4.1
Zhihai Wu,Zhiqiang Luo,Wen Sun,Yuanyuan Shi,Qi Ding
Allergic asthma is a prevalent form of asthma that is characterized primarily by airway inflammation. Jiegeng decoction (JGT) is a traditional Chinese herbal formula known for its anti-inflammatory properties and has been used to treat respiratory diseases for centuries. This study aimed to investigate the biological effects and mechanisms of action of JGT in improving allergic asthma. An experimental allergic asthma mouse model was established using ovalbumin. The results showed that JGT significantly improved inflammation cell infiltration in the lung tissue of allergic asthmatic mice and the inflammatory environment of Th2 cells in the bronchoalveolar lavage fluid while also reducing serum IgE levels. Subsequently, 38 components of JGT were identified through liquid chromatography–mass spectrometry. Network pharmacology revealed that regulating inflammation and immune responses is the primary biological process by which JGT improves allergic asthma, with Th2 cell differentiation and the JAK-STAT signaling pathway being the key mechanisms of action. Finally, qPCR, flow cytometry, and Western blotting were used to validate that JGT inhibited Th2 cell differentiation by blocking the JAK1-STAT6 signaling pathway in CD4+ T cells, ultimately improving allergic asthma. This study provides a novel perspective on the therapeutic potential of JGT in the treatment of allergic asthma.
研究领域:
药理学
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免疫学
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中医
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2024
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IF 4.8
Meng-Ke Liu,Juan-Juan Tang,Hao Li,Xu-Yang Chen,Jun-Ling Cai,Gui-Ying Lin,Kan-Yao Chen,Zhi-Peng Liu,Xiao-Fang Ji,Zhong-Jin Yang,Zi Li
Artemisitene (ATT), an artemisinin (ART) analog retaining the endoperoxide moiety and incorporating an additional α, β-unsaturated carbonyl structure, exhibits enhanced biological activities. However, its therapeutic effects on liver fibrosis remain unclear. In this study, we demonstrated that ATT significantly alleviated liver inflammation and fibrosis induced by carbon tetrachloride (CCL 4 ) in mice. ATT treatment markedly reduced the count of neutrophils in the liver, as well as macrophages in both the liver and spleen. Additionally, the frequencies of Th2 and Th17 cells were significantly lowered, while Th1 cells frequency and the Th1/Th2 index were notably increased. The frequency of ILC2 cells, correlated with ST2 and IL-33 expression levels, was also significantly lowered. Consistently, ATT inhibited NLRP3 inflammasome activation, which was positively associated with AST and ALT levels, and with the count of Neutrophils, macrophages, and ILC2 cells, but negatively correlated with Th1frequeny. Furthermore, liver fibrosis severity showed a significant positive correlation with neutrophil and Th17 cell counts in the liver, and a negative correlation with Th1 cell count and the Th1/Th2 index. Therefore, ATT alleviated CCL 4 -induced mice liver fibrosis through NLRP3 inflammasome inhibition and immunomodulation.
研究领域:
药理学
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免疫学
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肝病学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
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2025
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IF 16
Yichao Lu,Xinyu Shan,Jiaxin Huang,Huanli Zhou,Ying Zhu,Sijie Wang,Zhenyu Luo,Xu Liu,Xuemeng Guo,Yingying Shi,Yilong Hu,Huihui Liu,Junlei Zhang,Ping Huang,Lihua Luo,Jian You
Atopic dermatitis (AD) is a recurrent and chronic inflammatory skin condition characterized by a high lifetime prevalence and significant impairment of patients’ quality of life, primarily due to intense itching and discomfort. However, current pharmacological interventions provide only moderate efficacy and are frequently accompanied by adverse side effects. The immune-pathogenesis of AD involves dysregulation of the Th2 immune response and exacerbation of inflammation related to excessive reactive oxygen species (ROS). Therefore, to address these issues, in this study, we targeted the upstream pathogenesis by designing a pro-Th1 adjuvant nanoemulsion loaded with poly(I:C) and encapsulated with the ROS-scavenger vitamin E, termed PV-NE. PV-NE effectively rebalanced the Th1/Th2 immune response and reduced ROS levels both in vivo and ex vivo, leading to the restoration of immune balance in AD-affected skin and alleviation of symptoms such as lichenification and erythematous patches. In conclusion, our development of the reductive adjuvant nanosystem PV-NE demonstrates its biocompatibility and efficacy in combating AD progression without the use of immunosuppressant glucocorticoids. This has the potential to significantly impact the design and enhancement of pharmacotherapy in future clinical research aimed at curing AD.
研究领域:
皮肤病学
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免疫学
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纳米医学
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药理学
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产品关联
DOI
PubMed
高影响因子
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