IMMUNOLOGIC RESEARCH
·
2025
·Vol. 73
·期 1
·1-20
·
IF 3.1
Xu Cong,Lu Chenqi,Wang Wu,Wang Zhimin,Qiu Yang,Han Min,Yang Jun,Li Shanglin
Autoimmune hepatitis (AIH) is an immune-mediated liver disease that currently lacks viable drug treatment methods. This study is to explore the role of piceatannol (PIC) in ConA-induced AIH and the related mechanisms. A mouse model of AIH was established by injecting ConA (i.v.), and PIC was administered as an intervention. The protective effect of PIC was evaluated by the liver function, liver pathology, and serum levels of inflammatory factors. Subsequently, network pharmacology was used to predict the pathways and targets of PIC in the treatment of AIH, and the predicted results were validated using flow cytometry, molecular docking, surface plasmon resonance (SPR) and so on. Finally, the immunosuppressive effect of PIC was further validated in a mouse heart transplantation model. PIC can improve liver function decline and reduce pathological liver damage, as well as inhibit the increase of serum inflammatory factor levels in mice with AIH induced by ConA. The protective effect is achieved by suppressing the immune activity of T cells and macrophages through binding to c-Jun. PIC can also extend the survival of cardiac allografts and inhibit acute rejection reactions. These results indicated that PIC can significantly improve ConA-induced AIH in mice by inhibiting the immune activity of T cells and macrophages through binding to c-Jun. PIC can also extend the survival of cardiac allografts in mice and inhibit acute rejection responses. The above results indicated that PIC may serve as a promising immunosuppressant and be effective for AIH.
研究领域:
免疫学
·
肝病学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Mengling Zhong,Mingmei Feng,Xinlin Chen,Yuxin Zhang,Yupeng Wang,Peizhi Yuan,Tianyao Zhang,Zhipeng Han,Chenglun Tang,Qi Zhang,Yang Sun
Immunosuppression causing the host more vulnerable to pathogen invasion, increases the risk of malignant tumors and inflammatory diseases. Cordycepin possesses diverse pharmacological activities, including anti-inflammatory, antioxidant, and antitumor effects. However, the immunomodulatory mechanisms of cordycepin remain poorly understood. This study aimed to explore the immunoregulatory effect of cordycepin and elucidate its underlying mechanisms. In our study, cordycepin restored body weight, organ indices and ameliorated splenic damage in cyclophosphamide (CTX)-induced immunosuppressed mice. Cordycepin enhanced the proliferation of T and B lymphocytes stimulated by ConA and LPS. Cordycepin normalized the counts of white blood cells (WBC), lymphocytes (LYM), neutrophils (NEU) and eosinophils (EOS), and increased the levels of immunoglobulins (immunoglobulin A (IgA), IgM, IgG). Cordycepin also increased the production of pro-inflammatory cytokines IL-2 and IFN-γ, but decreased the level of inhibitory cytokines IL-10. Additionally, cordycepin reduced serum level of malondialdehyde (MDA), enhanced content of glutathione (GSH) and the enzymatic activities of superoxide dismutase (SOD) and catalase (CAT). Moreover, metabolomic analysis of spleen and serum revealed that cordycepin counteracted the metabolic disturbance induced by CTX, particularly regulating pyruvate metabolism pathway. Network pharmacology approaches suggested that cordycepin modulated metabolic and immune pathways by targeting EGFR. Furthermore, cordycepin reduced the protein level of phosphorylated EGFR and upregulated the protein expression of Nrf2, NQO1 and HO-1 in the spleens of immunosuppression mice. In conclusion, this study demonstrated that cordycepin ameliorated CTX-induced immunosuppression of mice by reversing metabolic dysfunction and activating Nrf2 pathway through regulating EGFR, indicating its potential as a therapeutic agent for immunosuppression.
研究领域:
药理学
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免疫学
·
生物化学
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代谢生物学
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肿瘤学
·
天然产物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Hangyi Wu,Xiaoyu Lu,Yuhan Hu,J. Baatarbolat,Zhihao Zhang,Yiping Liang,Youwen Zhang,Ye Liu,Huixia Lv,Xin Jin
Elesclomol (ES) as an efficient Cu ionophore can specifically transport Cu into mitochondria and disrupt intracellular Cu homeostasis. Extra intracellular Cu induces cuproptosis and chemodynamic therapy (CDT), which further cascades immunogenic cell death (ICD) and activates antitumor immune responses. However, the tumor immunosuppressive microenvironment (TIM) attenuates the efficiency of the immune response. Herein, a biomimic nanodrug (ECNM) is fabricated, of which ES, Cu 2+ and NLG919 (an IDO1 inhibitor) are integrated via a self-assembly process and subsequently coated with 4T1 cell membrane. ECNM can overcome the typical drawbacks of ES, ameliorating the stability and half-life of ES by membrane-coating and enhancing its tumor accumulation and internalization via homotypic targeting. It is worth mentioning that, the addition of NLG919 is also beneficial to the system circulation stability of ES and reduces the non-specific ES release. After internalization, ECNM dissociates via the glutathione-responsive process and exhibits comprehensive antitumor capabilities, including cuproptosis, CDT and TIM reversing, thereby eliciting ICD and optimizing the antitumor immune response. Furthermore, ECNM not only accelerates tumor regression but also gains a strong abscopal effect and displays the potential of tumor vaccination. Overall, ECNM can activate antitumor immunity via cuproptosis and CDT, together with TIM reversing, for cancer treatment.
研究领域:
肿瘤学
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纳米医学
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免疫治疗
✓ 已验证
DOI
高影响因子
Cell Death & Disease
·
2018
·Vol. 9
·期 3
·1-15
·
IF 5.638
Ding Yue,Liang Xiaoting,Zhang Yuelin,Yi Li,Shum Ho Cheung,Chen Qiulan,Chan Barbara P.,Fan Huimin,Liu Zhongmin,Tergaonkar Vinay,Qi Zhongquan,Tse Hung-fat,Lian Qizhou
Immunomodulatory activity of mesenchymal stem cells (MSCs) is largely mediated by paracrine factors. Our previous studies showed that activation of nuclear factor-kappa B (NF-κB) regulates cytokine/growth factor secretion by MSCs. This study aimed to elucidate the role of Rap1 (repressor/activator protein), a novel modulator involved in the NF-κB pathway, in regulating the immunomodulatory potency of MSCs in acute allograft rejection of heart transplantation. The immunosuppressive potency of wild-type MSCs (WT-MSCs) or Rap1-deficient MSCs (Rap1 −/− -MSCs) was examined in mice with acute allograft rejection following heart transplantation. With a combination of immunosuppressant rapamycin at a dose of 1 mg/kg/d, WT-MSCs notably prolonged the survival of the transplanted heart compared with Rap1 −/− -MSCs. Rap1 −/− -MSCs displayed a marked insensitivity to inhibit the mixed lymphocyte reaction (MLR) due to impaired cytokine production and a significantly reduced activity of NF-κB signaling in vitro . Finally, transplantation of encapsulated WT-MSCs greatly prolonged the survival of the heart allograft compared with encapsulated Rap1 −/− -MSCs. Our results indicate that Rap1 is essential to maintain the immunomodulatory function of MSCs. Deletion of Rap1 results in impaired immunomodulatory function of MSCs.
研究领域:
免疫学
·
干细胞研究
·
移植医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Qiang Chu,Yiru Zhang,Wen Chen,Ruoyi Jia,Xin Yu,Yaxuan Wang,Yonglu Li,Yangyang Liu,Xiang Ye,Lushuang Yu,Xiaodong Zheng
Immunosuppression refers to the suppression of the immune response. The immune function of immunocompromised people is not enough to resist bacterial, viral, fungal and other infections, leading to a series of diseases. A large number of experimental data show that polysaccharide compounds are immune modulators, which can enhance the body immunity with little toxic. Meanwhile, it can reduce the side effects of commonly used immunosuppressants, such as cytotoxicity, decreased ability of the body to fight infection, and inhibition of the reproduction of bone marrow hematopoietic cells. It can be used as oral or injectable drugs. In this study, a purified polysaccharide was primarily extracted from the flowers of Apios americana Medik (AAM), which can improve the immunosuppression induced by cyclophosphamide (CTX). The immunoenhancement effect of AFP was evaluated by measuring the body weight, immune organ index, cytokine secretion and antibody generated levels of CTX-induced mice. Our results showed that AFP could significantly improve the above immune indexes, which indicated AFP could alleviate immunosuppression induced by CTX. The study provided a theoretical basis for the promotion, development and application of AAM as a newly introduced food material.
研究领域:
免疫学
·
药理学
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植物学
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实验医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Infection and Drug Resistance
·
2023
·
IF 3.9
Lingna Xu,Ren-ai Xu,Dan Zhang,Shanshan Su,Hanyan Xu,Qing Wu,Yuping Li
Background: T helper 17 (Th17) lymphocytes play an important role in Aspergillus adaptive immune response against Aspergillus fumigatus, but there is little attention focused on the different types of immunosuppressive models in which invasive pulmonary aspergillosis (IPA) develops. In addition, the expression levels of signal transducer and activator of transcription 3 (STAT3)/retinoic acid-related orphan nuclear receptor gamma (RORγt)/interleukin (IL)-17A signaling pathway, which is involved in the regulation of Th17 cells, as well as whether there are differences between two types of IPA mice models, remain unknown.Materials and methods: Six to eight weeks old female BALB/c mice were treated with cortisone acetate or cyclophosphamide to establish the immunosuppressive mice models, and then, A. fumigatus inoculum was injected to form the IPA groups and sterile saline was injected to form the control groups. Flow cytometry was performed to measure the proportion of Th17 cells in CD4+ T cells in the peripheral blood, spleen, and lung of the mice. The expression of IL-17A, RORγt, and STAT3 mRNA was detected by real-time polymerase chain reaction. Concentrations of IL-6 in the plasma and bronchoalveolar lavage fluid were measured by enzyme-linked immunosorbent assay.Results: The proportion of Th17 in the peripheral blood and lung tissue in neutropenic IPA mice showed a more significant increase than in non-neutropenic IPA mice (P<0.01). The IL-6 protein also showed the same trend in plasma and bronchoalveolar lavage fluid (P<0.01). Compared with the control groups, the expression of IL-17A at mRNA level in the lung was significantly increased, while RORγt/STAT3 mRNA was significantly decreased in the IPA groups (P<0.01).Conclusion: The expression of RORγt and STAT3 mRNA in the lung tissue in both groups was significantly decreased. IL-17 may play a negative role in the defense against Aspergillus through uprating IL-6.
研究领域:
免疫学
·
微生物学
·
分子生物学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Yinghan Guo,Lulu Jin,Zhipeng Shen,Linfeng Fan,Xian Yu,Yirui Kuang,Lingxin Cai,Jiayin Zhou,Zihang Chen,Feng Yan,Jianmin Zhang,Minfeng Tong,Jianlie Yuan,Zhengwei Mao,Gao Chen
The malignant interaction between tumor cells and immune cells is one of the important reasons for the rapid progression and refractoriness of glioblastoma (GBM). As an essential metabolic center of M2 macrophages, the inhibition of protein kinase RNA-like endoplasmic reticulum kinase (PERK) leads to the reduction of M2 macrophages. Nevertheless, the restriction of the blood-brain barrier (BBB) and non-specific cell targeting hinder the application of PERK inhibitors in GBM. Herein, the optimal NP-M-M2pep is developed successfully, which has shown the capacity of BBB penetration and specific targeting of M2 microglia. In addition to inhibiting the polarization of M2 microglia, the administration of iPERK@NP-M-M2pep reprogrammed M2 microglia into M1 ones in vitro via PERK/HIF-1α/glycolysis pathway. Efficient brain accumulation of nanoparticles is achieved after tail vein injection, with effective inhibition of GBM progression after one course of treatment. The glioma-associated microglia and macrophages (GAM) with M2 type are induced to M1 and the immunosuppressive TME is remodeled by upregulating immunostimulatory cells and downregulating immunosuppressive cells. In summary, the biomimetic membrane vesicles (BMVs) specifically delivered iPERK to GAMs offer an inspiring strategy to reprogram microglia polarization, re-educate immunosuppressive TME, and inhibit the progression of GBM.
研究领域:
肿瘤学
·
神经科学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2025
·
IF 5.9
Laibing Sun,Xinyan Bai,Yanna Hu,Lingyu Li,Xiaoming Lu,Xuguang Qiao
In this study, we comparatively investigated the immunomodulatory effects of garlic oligosaccharides (GPs) of different molecular weights (GPs-U2, GPs-U1 and GPs-U0.3) on RAW264.7 macrophages in vitro and cyclophosphamide (CY)-induced immunosuppressed mice model (C57BL/6 male mice) in vivo. All three GPs displayed high immunomodulatory effects in enhancing cell viability and promoting the secretion of cytokines ( i.e. tumor necrosis factor- α (TNF- α ), interleukin (IL)-1 β and IL-10) in RAW264.7 macrophages in vitro , especially GPs-U2 exhibited the highest immune activity. Furthermore, GPs-U2 showed good immune effects in CY-induced immunosuppressed mouse model in vivo by regulating cytokine secretion, antioxidant levels, goblet cells numbers, expression of tight junction proteins (TJs) and short-chain fatty acids (SCFAs) content. In addition, GPs-U2 maintained mucosal immunity by increasing the abundance of Bacteroidota and Verrucomicrobiota and decreasing the abundance of Firmicutes . These findings support the immune-enhancing effects of GPs-U2 in vitro and in vivo , and provide a scientific basis for the rational use of GPs to alleviate immunosuppression and related diseases.
研究领域:
免疫学
·
分子生物学
·
微生物组学
✓ 已验证
产品关联
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Haiyang Wang,Yixuan Hou,Taian Lin,Ihsan Ullah,Qing Xu,Ye Liu,Taosha Jin,Yangning Zhang,Youyong Yuan
Radiotherapy (RT) is commonly employed to prevent postoperative recurrence, typically delivered in fractionated doses to mitigate side effects. However, multi-course RT frequently leads to radiation resistance and immunosuppression. In this study, a sono-responsive hydrogel that enables fractionated releases of PROteolysis TArgeting Chimeras (PROTAC) in response to ultrasound (US) pulses is presented. This system targets bromodomain-containing protein 4 (BRD4) and releases the PROTAC at the tumor site before each course of RT. This release inhibits DNA repair mechanisms and reduces myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), thereby mitigating RT resistance and immune suppression. This strategy significantly improves the therapeutic efficacy of postoperative RT, reducing the risk of tumor recurrence. Overall, this work proposes an easy-to-implement strategy for overcoming challenges in resistance and immunosuppression in multi-course postoperative RT.
研究领域:
生物医学工程
·
肿瘤学
·
药学
·
免疫学
·
放射生物学
✓ 已验证
产品关联
DOI
高影响因子
Nutrients
·
2024
·Vol. 16
·期 9
·1395
·
IF 4.8
Xinru Du,Yongheng Yan,Yufeng Dai,Ruijie Xu
Numerous studies have investigated the immunomodulatory effects of yogurt, but the underlying mechanism remained elusive. This study aimed to elucidate the alleviating properties of yogurt on immunosuppression and proposed the underlying mechanism was related to the metabolite D-lactate. In the healthy mice, we validated the safety of daily yogurt consumption (600 μL) or D-lactate (300 mg/kg). In immunosuppressed mice induced by cyclophosphamide (CTX), we evaluated the immune regulation of yogurt and D-lactate. The result showed that yogurt restored body weight, boosted immune organ index, repaired splenic tissue, recovered the severity of delayed-type hypersensitivity reactions and increased serum cytokines (IgA, IgG, IL-6, IFN-γ). Additionally, yogurt enhanced intestinal immune function by restoring the intestinal barrier and upregulating the abundance of Bifidobacterium and Lactobacillus. Further studies showed that D-lactate alleviated immunosuppression in mice mainly by promoting cellular immunity. D-lactate recovered body weight and organ development, elevated serum cytokines (IgA, IgG, IL-6, IFN-γ), enhanced splenic lymphocyte proliferation and increased the mRNA level of T-bet in splenic lymphocyte to bolster Th1 differentiation. Finally, CTX is a chemotherapeutic drug, thus, the application of yogurt and D-lactate in the tumor-bearing mouse model was initially explored. The results showed that both yogurt (600 μL) and D-lactate (300 mg/kg) reduced cyclophosphamide-induced immunosuppression without promoting tumor growth. Overall, this study evaluated the safety, immune efficacy and applicability of yogurt and D-lactate in regulating immunosuppression. It emphasized the potential of yogurt as a functional food for immune regulation, with D-lactate playing a crucial role in its immunomodulatory effects.
研究领域:
免疫学
·
营养学
·
药理学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Signal Transduction and Targeted Therapy
·
2024
·Vol. 9
·期 1
·1-18
·
IF 40.8
Yang Chuan,Wang Xueping,To Kenneth K. W.,Cui Caimei,Luo Min,Wu Shaocong,Huang Lamei,Fu Kai,Pan Can,Liu Zeyu,Fan Teng,Yang Caibo,Wang Fang,Fu Liwu
Circulating tumor cells (CTCs) are precursors of distant metastasis in a subset of cancer patients. A better understanding of CTCs heterogeneity and how these CTCs survive during hematogenous dissemination could lay the foundation for therapeutic prevention of cancer metastasis. It remains elusive how CTCs evade immune surveillance and elimination by immune cells. In this study, we unequivocally identified a subpopulation of CTCs shielded with extracellular vesicle (EVs)-derived CD45 (termed as CD45 + CTCs) that resisted T cell attack. A higher percentage of CD45 + CTCs was found to be closely correlated with higher incidence of metastasis and worse prognosis in cancer patients. Moreover, CD45 + tumor cells orchestrated an immunosuppressive milieu and CD45 + CTCs exhibited remarkably stronger metastatic potential than CD45 − CTCs in vivo. Mechanistically, CD45 expressing on tumor surfaces was shown to form intercellular CD45-CD45 homophilic interactions with CD45 on T cells, thereby preventing CD45 exclusion from TCR-pMHC synapse and leading to diminished TCR signaling transduction and suppressed immune response. Together, these results pointed to an underappreciated capability of EVs-derived CD45-dressed CTCs in immune evasion and metastasis, providing a rationale for targeting EVs-derived CD45 internalization by CTCs to prevent cancer metastasis.
研究领域:
肿瘤学
·
免疫学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
·
2024
·
IF 3.7
Dong Liu,Tingting Hou,Chunye Geng,Lu Song,Xuefeng Hou,Yanjun Chen,Fang Wang,Wei Wang,Bangxing Han,Leilei Gao
Poor stability and difficult uptake of natural polysaccharides have been the main problems in their application. The purpose of this study was to optimize the preparation conditions of Polygonatum cyrtonema Hua polysaccharides liposomes (PCPL) and to investigate the immune enhancement activity of PCPL in vitro and in vivo, with a view to discovering new ways of natural polysaccharide application. The optimal preparation conditions of PCPL were as follows: the adding amount of Tween 80 of 0.5 %, the ultrasound time of 2 min and the ultrasound times of once. Under these conditions, the entrapment efficiency, drug loading rate and particle size of PCPL were 38.033 %±0.050, 2.172 %±0.003 and 146 nm, which indicated that PCPL with small particle size could be prepared by the reverse-phase evaporation method. Furthermore, PCPL promoted proliferation, phagocytosis, and secretion of nitric oxide and related cytokines in RAW264.7 cells. Moreover, PCPL improved spleen and thymus indices, increased the number or proportion of red blood cells, platelets, and lymphocytes in the blood, and ameliorated spleen and thymus atrophy in immunosuppressed mice. This study provides a new idea for applying Polygonatum cyrtonema Hua polysaccharides (PCP) and references for studying other polysaccharides.
研究领域:
药学
·
免疫学
·
生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）