INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2012
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IF 2.453
Ye Liu,Shoufeng Zhang,Fei Zhang,Rongliang Hu
Four botanical polysaccharide preparations (from Astragalus , Echinacea , wolfberry, and kelp) were evaluated as immunopotentiators/adjuvants of a veterinary rabies vaccine. Results showed that lymphocyte proliferation and some cytokines were significantly elevated, with cellular immune responses skewed towards Th1 and Tc1. All four polysaccharides produced accelerated and enhanced effects on rabies-neutralizing antibody responses in mice and dogs. The results also indicated that certain botanical polysaccharides could be used in rabies vaccine formulations for early and persistent prophylaxis.
研究领域:
免疫学
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兽医学
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植物化学
✓ 已验证
DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-17
·
IF 15.7
Wen Zhenzhen,Liu Tong,Xu Xutao,Acharya Nandini,Shen Zhida,Lu Yunkun,Xu Junjie,Guo Ke,Shen Shuying,Zhao Yuening,Wang Pinli,Li Shumin,Chen Weiyu,Li Hui,Ding Yimin,Shang Min,Guo Hongshan,Hou Yu,Cui Bijun,Shen Manlu,Huang Youling,Pan Ting,Qingqing Wang,Cao Qian,Wang Kai,Xiao Peng
Overcoming immunosuppression in the tumor microenvironment (TME) is crucial for developing novel cancer immunotherapies. Here, we report that IL-16 administration enhances the polarization of T helper 1 (Th1) cells by inhibiting glutamine catabolism through the downregulation of glutaminase in CD4 + T cells and increases the production of Th1 effector cytokine IFN-γ, thus improving anti-tumor immune responses. Moreover, we find that establishing an IL-16-dependent, Th1-dominant TME relies on mast cell-produced histamine and results in the increased expression of the CXCR3 ligands in tumor-associated macrophages (TAM), thereby improving the therapeutic effectiveness of immune checkpoint blockade (ICB). Cancer patients exhibit impaired production of IL-16, which correlates with poorer prognosis. Additionally, low IL-16 production is associated with unresponsiveness to immunotherapy in cancer patients. Collectively, our findings provided new insights into the biological function of IL-16, emphasizing its potential clinical significance as a therapeutic approach to augment anti-tumor immunity and sensitize ICB-based cancer immunotherapy.
研究领域:
免疫学
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肿瘤学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
IMMUNITY
·
2021
·
IF 31.745
Ling-jie Huang,Xin-tao Mao,Yi-yuan Li,Dan-dan Liu,Ke-qi Fan,Rong-bei Liu,Ting-ting Wu,Hao-li Wang,Yu Zhang,Bing Yang,Cun-qi Ye,Jiang-yan Zhong,Ren-jie Chai,Qian Cao,Jin Jin
Summary Inflammatory bowel disease (IBD) mainly includes Crohn’s disease (CD) and ulcerative colitis (UC). Immune disorders play an essential role in the pathogenesis of these two IBDs, but the differences in the immune microenvironment of the colon and their underlying mechanisms remain poorly investigated. Here we examined the immunological features and metabolic microenvironment of untreated individuals with IBD by multiomics analyses. Modulation of CD-specific metabolites, particularly reduced selenium, can obviously shape type 1 T helper (Th1) cell differentiation, which is specifically enriched in CD. Selenium supplementation suppressed the symptoms and onset of CD and Th1 cell differentiation via selenoprotein W (SELW)-mediated cellular reactive oxygen species scavenging. SELW promoted purine salvage pathways and inhibited one-carbon metabolism by recruiting an E3 ubiquitin ligase, tripartite motif-containing protein 21, which controlled the stability of serine hydroxymethyltransferase 2. Our work highlights selenium as an essential regulator of T cell responses and potential therapeutic targets in CD.
研究领域:
免疫学
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胃肠病学
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代谢组学
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系统生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2020
·
IF 3.943
Meng Wang,Jinglan Zhang,Huayan Zhao,Dingming Wan,Zhongxing Jiang
Graft-versus-host disease (GVHD) causes significant mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Berberine (BBR) is primarily used to alleviate inflammation caused by autoimmune disorders. Herein the effect of BBR and cyclosporine A (CsA) on GVHD prevention in murine models is explored. Acute GVHD was induced by total body irradiation and tail vein injection with the mixture of bone marrow cells and spleen lymphocytes. Then models were treated with BBR (10 mg/kg), CsA (5 mg/kg) or the combination of BBR and CsA (10 mg/kg and 5 mg/kg) once a day for 10 days. The survival rate, weight loss and GVHD index were monitored. Then the histological changes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, apoptosis and the levels of inflammatory cytokines, oxidative stress and nuclear factor-κB (NF-κB) signaling in liver and intestine were analyzed. Moreover, the levels of inflammatory cytokines and oxidative stress, and the count of T helper 1 (Th1) cells and Th17 cells in peripheral blood were determined. The results showed that BBR reduced GVHD-induced weight loss and GVHD index scores, attenuated liver and intestinal injury, and inhibited ALT and AST activities, inflammation, oxidative stress and NF-κB activation in liver and intestine. Additionally, BBR inhibited inflammation and reduced Th1 cell counts but had no effect on Th17 cell counts. Interestingly, the concomitant therapy of BBR and CsA was more potent than either BBR or CsA and effectively elevated the survival rate of GVHD models. This present study provides a new therapeutic strategy for alleviation of acute GVHD.
研究领域:
免疫学
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药理学
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血液学
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移植学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Xudong Xie,Weixian Hu,Yue An,Yuheng Liao,Shengming Zhang,Yanzhi Zhao,Kangkang Zha,Wenqian Zhang,Zhenhe Zhang,Fan Xia,Bobin Mi,Benjie Zhou,Hankun Hu,Mengfei Liu,Guohui Liu
Diabetic wounds are characterized by an imbalance between impaired angiogenesis and persistent pro-inflammatory immune responses, leading to chronic non-healing. Under hyperglycemic and oxidative stress conditions, the glycolytic function of endothelial cells is significantly compromised. However, solely enhancing angiogenesis does not effectively promote diabetic wound healing due to concomitant dysregulation of the local immune microenvironment, which further suppresses vascularization. Notably, Th1 cells dominate the diabetic wound immune milieu and exacerbate inflammatory responses, thereby aggravating immune imbalance. Thus, an optimal therapeutic strategy should simultaneously target both inflammatory dysregulation and vascular dysfunction. To address the phenomenon of cell-specific metabolic reprogramming within diabetic wounds, where glycolytic activity is impaired in endothelial cells yet enhanced in Th1 cells, this study developed a glucose-responsive NG@B87@HA hydrogel system designed to reprogram the local metabolic network and modulate Th1 cell metabolism while restoring endothelial function. The hydrogel incorporates nanoparticles functionalized with CXCR3 antibody to specifically target Th1 cells and deliver the glycolysis inhibitor Bay87-2243 (B87), thereby suppressing their glycolytic flux and inflammatory activity via inhibition of the HIF-1α–GLUT1 signaling axis. Simultaneously, naringin (NG), which acts as a crosslinker, forms dynamic boronic ester bonds with HA-PBA and PVA, enabling glucose-dependent responsiveness. This mechanism not only mitigates local oxidative stress but also enhances the tube-forming capacity of endothelial cells, ultimately promoting angiogenesis. The results demonstrated that the NG@B87@HA hydrogel effectively restores the dysregulated metabolic network in diabetic wounds. By concurrently rectifying immune microenvironment imbalance and endothelial dysfunction, this system provides a novel therapeutic strategy for accelerating diabetic wound healing.
✓ 已验证
产品关联
DOI
高影响因子
ENVIRONMENTAL SCIENCE & TECHNOLOGY
·
2024
·
IF 10.8
Xiuxiu Yao,Wendi Huo,Yuchen Wang,Dongfang Xia,Yan Chen,Yuhua Tang,Huayong Tang,Wenjiang Yang,Yu Liu,Jingquan Xue,Qing Yuan,Xueyun Gao,Kai Cao
The presence of low-dose radiation (LDR) in the environment has become more prevalent. However, the effect of LDR exposure on the immune system remains elusive. Here, we interestingly found that LDR specifically elevated the percentage of CD4+IFNγ+ Th1 splenocytes, both in vitro and in vivo, without affecting the percentage of CD8+IFNγ+ Tc1 cells and regulatory T cells. A similar phenomenon was found in T cells from peripheral blood. Mechanistically, we found that LDR can induce mitochondrial damage, which stimulated the STING signaling pathway, leading to the enhanced expression of T-bet, the master transcriptional factor of Th1-cell differentiation. The specific STING signal inhibitor can abrogate the effect of LDR on Th1 differentiation, confirming the central role of the STING pathway. To further validate the immunoregulatory role of LDR, we exposed mice with whole body LDR and evaluated if LDR could protect mice against triple-negative breast cancer through enhanced antitumor immunity. As expected, LDR significantly delayed tumor development and promoted cell death. Meanwhile, LDR resulted in increased tumor-infiltrating Th1 cells, while the proportion of Tc1 and Treg cells remained unchanged. Furthermore, the infiltration of antitumor macrophages was also increased. In summary, we revealed that environmental LDR could specifically regulate Th1 T-cell activities, providing critical information for the potential application of LDR in both clinical and nonclinical settings.
研究领域:
免疫学
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肿瘤学
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放射生物学
✓ 已验证
DOI
PubMed
高影响因子
Human Cell
·
2024
·
IF 3.4
Wang Meng,Li Qiu-Jie,Zhao Hua-Yan,Zhang Jing-Lan
Lethal graft-versus-host disease (GVHD) is the major complication of allogeneic hematopoietic stem-cell transplantation (Allo-HSCT). Pyruvate kinase M2 (PKM2) is essential for CD4+ T-cell differentiation. Using the well-characterized mouse models of Allo-HSCT, we explored the effects of TEPP-46-induced PKM2 tetramerization on GVHD and graft-versus-leukemia (GVL) activity. TEPP-46 administration significantly improved the survival rate of GVHD. The severity of GVHD and histopathological damage of GVHD-targeted organs were obviously alleviated by PKM2 tetramerization. Additionally, tetramerized PKM2 inhibited the activation of NF-κB pathway and decreased the inflammation level of GVHD mice. PKM2 tetramerization blocked Th1 and Th17 cell differentiation and secretion of pro-inflammatory cytokine (IFN-γ, TNF-α, and IL-17). Meanwhile, differentiation of Treg cells and IL-10 secretion were promoted by tetramerized PKM2. These findings demonstrated that PKM2 enhanced the augment of Th1 and Th17 cells to accelerate the progression of GVHD, and allosteric activation of PKM2 targeted Th1 and Th17 cells attenuated GVHD. Furthermore, we also confirmed that TEPP-46 administration did not compromise GVL activity and resulted in slightly improvement of leukemia-free survive. Thus, targeting Th1 and Th17 cell response with PKM2 allosteric activator may be a promising therapeutic strategy for GVHD prevention while preserving the GVL activity in patients receiving Allo-HSCT. Graphical abstract
研究领域:
免疫学
·
血液学
·
移植学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Yaqiong Liu,Fang Wu,Ming Zhang,Yutong Jin,Xinlei Yuan,Yanling Hao,Lishui Chen,Bing Fang
Human milk oligosaccharides could prevent pathogenic bacterial infections in neonates; however, direct in vivo anti-infection evidence was still lacking. Here, we systematically evaluated the effects of 2′-fucosyllactose (2′-FL) and 3′-sialyllactose (3′-SL) on the structural development and functional maturation in neonates and their defense against enteroaggregative Escherichia coli infection. It was found that supplementation with 2′-FL and 3′-SL improved the resistance of weaned mice to enteroaggregative E. coli. The mechanism related to the promotion of 2′-FL and 3′-SL in the maturation of intestinal mucosal immunity by promoting stem cell differentiation, mucus layer integrity, and tight junction formation. 2′-FL and 3′-SL significantly increased the ratio of Th1 and Treg cells in the lamina propria, contents of short-chain fatty acids, as well as the serum content of IgA. This study lays a theoretical basis for the application of 2′-FL and 3′-SL in infant formula, as well as the development of intestinal health products.
研究领域:
儿科
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免疫学
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微生物学
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营养科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2022
·
IF 16.874
Jiangchao Wu,Xun Wang,Li Chen,Jianing Wang,Junlei Zhang,Jianghui Tang,Yongtao Ji,Jinyuan Song,Lin Wang,Yaxing Zhao,Hui Zhang,Taohong Li,Jianpeng Sheng,Dong Chen,Qi Zhang,Tingbo Liang
Rationale Hypoxia in tumor microenvironment (TME) represents an obstacle to the efficacy of immunotherapy for pancreatic ductal adenocarcinoma (PDAC) through several aspects such as increasing the expression of immune checkpoints or promoting fibrosis. Reversing hypoxic TME is a potential strategy to improve the validity of immune checkpoint blockade (ICB). Methods Here, we synthesized polydopamine-nanoparticle-stabilized oxygen microcapsules with excellent stabilization, bioavailability, and biocompatibility for direct oxygen delivery into tumor sites by interfacial polymerization. Results We observed oxygen microcapsules enhanced the oxygen concentration in the hypoxia environment and maintained the oxygen concentration for a long period both in vitro and in vivo . We found that oxygen microcapsules could significantly improve the efficiency of ICB against PDAC in vivo. Mechanismly, combined treatments using oxygen microcapsules and ICB could reduce the infiltration of tumor-associated macrophages (TAMs) and polarized pro-tumor M2 macrophages into anti-tumor M1 macrophages. In addition, combined treatments could elevate the proportion of T helper subtype 1 cells (Th1 cells) and cytotoxic T lymphocytes cells (CTLs) to mediate anti-tumor immune response in TME. Conclusion In summary, this pre-clinical study indicated that reversing hypoxia in TME by using oxygen microcapsules was an effective strategy to improve the performances of ICB on PDAC, which holds great potential for treating PDAC in the future.
研究领域:
肿瘤学
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免疫治疗
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纳米技术
·
癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Immunity Inflammation and Disease
·
2024
·Vol. 12
·期 2
·e1177
·
IF 3.1
Nannan Pang,Shabaaiti Tudahong,Yuejie Zhu,Jiang He,Chunxia Han,Gang Chen,Weiguo Wang,Jing Wang,Jianbing Ding
Background Acute graft-versus-host disease (aGVHD) arises from the imbalance of host T cells. Galectin-9 negatively regulates CD4 effector T cell (Th1 and Th17) function by binding to Tim-3. However, the relationship between Galectin-9/Tim-3 and CD4 + T subsets in patients with aGVHD after Haplo-HSCT (haploidentical peripheral blood hematopoietic stem cell transplantation) has not been fully elucidated. Here, we investigated the role of Galectin-9 and CD4 + T subsets in aGVHD after haplo-HSCT. Methods Forty-two patients underwent Haplo-HSCT (26 without aGVHD and 16 with aGVHD), and 20 healthy controls were included. The concentrations of Galectin-9, interferon-gamma (IFN-γ), interleukin (IL)-4, transforming growth factor (TGF)-β, and IL-17 in the serum and culture supernatant were measured using enzyme-linked immunosorbent assay or cytometric bead array. The expression levels of Galectin-9, PI3K, p-PI3K, and p-mTOR protein were detected by western blot analysis. Flow cytometry was used to analyze the proportions of CD4 + T cell subsets. Bioinformatics analysis was performed. Results In patients with aGVHD, regulatory T (Treg) cells and Galectin-9 decreased, and the Th1, Th17, and Treg cells were significantly imbalanced. Moreover, Treg and Galectin-9 were rapidly reconstituted in the early stage of patients without aGVHD after Haplo-HSCT, but Th17 cells were reconstituted slowly. Furthermore, Tim-3 upregulation on Th17 and Th1 cells was associated with excessive activation of the PI3K/AKT pathway in patients with aGVHD. Specifically, in vitro treatment with Galectin-9 reduced IFN-γ and IL-17 production while augmenting TGF-β secretion. Bioinformatics analysis suggested the potential involvement of the PI3K/AKT/mTOR pathway in aGVHD. Mechanistically, exogenous Galectin-9 was found to mitigate aGVHD by restoring the Treg/Teffs (effector T cells) balance and suppressing PI3K. Conclusion Galectin-9 may ameliorate aGVHD after haplo-HSCT by modulating Treg/Teffs balance and regulating the PI3K/AKT/mTOR pathway. Targeting Galectin-9 may hold potential value for the treatment of aGVHD.
研究领域:
免疫学
·
血液学
·
移植学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Scientific Reports
·
2022
·Vol. 12
·期 1
·1-15
·
IF 4.996
Dong Hao,Feng Chenjie,Cai Xiyunyi,Hao Yuanyuan,Gu Xinyue,Cai Lei,Wu Shuting,Chen Jiamin,Liu Zhou,Xie Wen,Lu Xuanren,Qian Hongfa,Liu Yulin,Cao Yiming,Zhu Junlin,Xu Jiayi,Zhou Yanjie,Ma Shuangyu,Yang Sha,Shi Yufeng,Yu Haojiang,Shi Minjie,Wang Yurong,Gu Harvest F.,Fan Lei,Wu Liang
7-Met, a derivative of soybean isoflavone, is a natural flavonoid compound that has been reported to have multiple signaling pathways regulation effects. This study investigated the therapeutic effects of 7-Met on mice with atopic dermatitis induced by fluorescein isothiocyanate (FITC), or oxazolone (OXZ). 7-Met ameliorated FITC or OXZ-induced atopic dermatitis symptoms by decreasing ear thickness, spleen index, mast cell activation, neutrophil infiltration and serum IgE levels in female BALB/c mice. In FITC-induced atopic dermatitis mice, 7-Met reduced Th1 cytokines production and regulated Th1/Th2 balance by downregulating the secretion of thymic stromal lymphopoietin (TSLP) via inactivation of the NF-κB pathway. In OXZ-induced atopic dermatitis, 7-Met functioned through the reduction of Th17 cytokine production. Our study showed that 7-Methoxyisoflavone alleviated atopic dermatitis by regulating multiple signaling pathways and downregulating chemokine production.
研究领域:
免疫学
·
药理学
·
皮肤病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-18
·
IF 14.7
Tang Xudong,Shang Yangyang,Yang Hong,Song Yalan,Li Shan,Qin Yusi,Song Jingyi,Chen Kang,Liu Yang,Zhang Dinglin,Chen Lei
The PD-1/PD-L1 pathway in mucosal immunity is currently actively explored and considered as a target for inflammatory bowel disease (IBD) treatment. However, systemic PD-L1 administration may cause unpredictable adverse effects due to immunosuppression. Here we show that reactive oxygen species (ROS)-responsive nanoparticles enhance the efficacy and safety of PD-L1 in a mouse colitis model. The nanoparticles control the accumulation and release of PD-L1 fused to Fc (PD-L1-Fc) at inflammatory sites in the colon. The nanotherapeutics shows superiority in alleviating inflammatory symptoms over systemic PD-L1-Fc administration and mitigates the adverse effects of PD-L1-Fc administration. The nanoparticles-formulated PD-L1-Fc affects production of proinflammatory and anti-inflammatory cytokines, attenuates the infiltration of macrophages, neutrophils, and dendritic cells, increases the frequencies of Treg, Th1 and Tfh cells, reshapes the gut microbiota composition; and increases short-chain fatty acid production. In summary, PD-L1-Fc-decorated nanoparticles may provide an effective and safe strategy for the targeted treatment of IBD.
研究领域:
药理学
·
免疫学
·
纳米技术
·
胃肠病学
✓ 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）