INFLAMMATION
·
2020
·Vol. 43
·期 5
·1780-1788
·
IF 3.212
Zhang Liming,Huang Yang,Cui Xiaoxiao,Tan Xiao,Zhu Ying,Zhou Wenjun,Wang Chaokui,Yuan Gangxiang,Cao Qingfeng,Su Guannan,Kijlstra Aize,Yang Peizeng
Previous studies have pointed out that indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme initiating tryptophan metabolism, plays a role in the regulation of the immune system. This project was designed to investigate the potential role of IDO in monocyte-derived dendritic cells (moDCs) obtained from active Vogt-Koyanagi-Harada (VKH) disease patients. In this study, we found that the IDO mRNA expression and enzyme activity were increased in active VKH patients as compared with healthy controls and patients in remission. To investigate the role of IDO in immune regulation, an effective inhibitor 1-methyl-L-tryptophan (1-MT) was used to suppress its activity in DCs. The results showed that inhibition of IDO with 1-MT significantly decreased the expression of DC marker CD86. IDO inhibition did not affect the cytokine production of IL-6, IL-1β, TNF-α, IL-10, and TGF-β in DCs. Downregulation of IDO in DCs also led to the reduction of regulatory T (Treg) cells and an increased CD4 + T cell proliferation. Treatment with 1-MT did not affect the phosphorylation of the MAPK pathway in DCs. In general, our study suggests that IDO may play an important role in the pathogenesis of VKH disease by regulating DC and CD4 + T cell function. Tryptophan deficiency and kynurenine accumulation may account for the complicated effects of IDO. Further research is needed to study the precise tryptophan metabolites that may limit immune responses in VKH disease.
研究领域:
免疫学
·
眼科
·
分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
·
IF 4.845
Min Jiang,Kaiyong He,Tong Qiu,Jiahui Sun,Qi Liu,Xueqiong Zhang,Hua Zheng
We induced changes in the tumor microenvironment (TME) through the synergistic actions of two drugs used in breast cancer therapy. The anti-fibrotic drug silibinin (SLB) targets tumor-associated fibroblasts and exerts immune-mediated anti-cancer effects. IPI-549, an efficient and highly selective phosphoinositide-3-kinase-gamma (PI3Kγ) inhibitor, was applied to alter the balance of immunosuppressive cells by inhibiting PI3Kγ molecules; it also promotes anti-tumor immunity. We developed nanoparticle formulations to encapsulate both drugs into the targeting carrier aminoethyl anisamide-polyethylene glycol-polycaprolactone (AEAA-PEG-PCL) respectively. The drugs were intravenously delivered in mice and resulted in an increase in anti-tumor efficacy and apoptotic tumor tissue compared with either IPI-549 or SLB alone in 4T1 breast cancer cell-derived tumors. Furthermore, a significant reduction in regulatory T (Treg) cells and myeloid suppressor cells (MDSCs) was observed. A normalized TME structure was also observed, including angiogenesis suppression, antifibrotic effects and the inhibition of collagen formation in the tumor tissue, significantly enhancing the anti-tumor effects. In summary, this combination strategy may offer an alternative treatment for breast cancer.
研究领域:
肿瘤学
·
药理学
·
免疫学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Shiru Huang,Han He,Hanxi Li,Chongyang Li,Fu Wang,Yuan Hu,Youping Liu,Lin Chen,Hongping Chen
Atractylodis macrocephalae Rhizoma (AM), a widely used Chinese herb for treating spleen deficiency diarrhea (SDD), is rich in polysaccharides. However, the precise mechanism underlying the antidiarrheal effects of Atractylodis macrocephalae Rhizoma polysaccharide (AMP) remains unclear. In this study, AMP, with a molecular weight of 69 kDa, is isolated from AM and consists of Glc, Gal, and Ara in a molar ratio of 84.16:6.51:9.33. FTIR and NMR analyses indicate that AMP features a linear backbone of →4,6)-α-D-Glc p -(1→ with branches of →3)-β-D-Glc p -(1→, terminating in →2,4)-β-D-Gal p -(1→. Animal models of SDD induced by Folium sennae demonstrate that AMP alleviates diarrhea symptoms, mitigates colon damage, and enhances spleen index, thymus index, and the expression of CD4 + CD25 + Foxp3 + Treg cells. Further, the potential mechanisms for AMP's antidiarrheal action are explored through the comprehensive approach integrating intestinal flora, polysaccharide utilization loci, short-chain fatty acids (SCFAs), and metabolomics. AMP reduces the abundance of pathogenic c_ Clostridia while promoting beneficial o_Bacteroidales and f_Muribaculaceae, influencing SCFAs production via its strong binding affinities with SusD, GH2, and GH43. This modulation is linked to alterations in linoleic acid metabolism, alpha-linolenic acid metabolism, and primary bile acid biosynthesis. In conclusion, AMP demonstrates significant potential as a therapeutic agent for SDD.
研究领域:
药理学
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微生物学
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免疫学
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代谢组学
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中医药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AUTOIMMUNITY
·
2020
·
IF 2.125
Cao Yongjun,Qiao Nan,Sun Yumeng,Jin Xiaowen,Wen Weibo
Dioscin has been used as a treatment for Hashimoto’s thyroiditis (HT) in China. However, the molecular mechanisms governing the modes of action of dioscin have not been elucidated. In this study, flow cytometry and Western blotting were used to identify the proportions of CD4+CD25+ regulatory T (Treg) cells and the expression of forkhead box P3 (Foxp3) and SUMO-specific protease 1 (SENP1) in HT patients’ peripheral blood mononuclear cells (PBMCs). A pTg-induced rat model of HT was established by injection of 100 μg pTg. Then, the model rats were randomly divided into three groups (n = 5): control (NC), model (HT) and dioscin treatment. After oral administration of dioscin each day for two weeks, CD4+CD25+Foxp3+ Treg cells were analysed by flow cytometry, and the protein expression levels of SENP1, Foxp3, SUMO-1 and SUMO-2/3 were measured by Western blotting. Co-immunoprecipitation (Co-IP) was used to identify the SUMOylation of interferon regulatory factor 4 (IRF4). The results showed that the proportions of CD4+CD25+ Treg cells and the expression of Foxp3 were significantly decreased in HT patients, but the expression of SENP1 was enhanced compared to healthy controls (HCs). However, compared to the pTg-induced HT rat group, the expression of Foxp3, SUMO-1, and SUMO-2/3 and the proportions of CD4+CD25+Foxp3+ Treg cells were increased, whereas the expression of SENP1 was decreased, in the dioscin-treated group. Furthermore, the SUMOylation of IRF4 was increased after SENP1 was knocked down. The results of our study indicate that dioscin can promote the differentiation of the CD4+CD25+Foxp3+ Treg cells and subsequently upregulate the SUMOylation of IRF4 by downregulating SENP1 expression.
研究领域:
免疫学
·
分子生物学
·
内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2023
·
IF 29.4
Xiaoyu Yin,Lintao Wang,Yiming Niu,Daping Xie,Qingwen Zhang,Jian Xiao,Lei Dong,Chunming Wang
Hair loss affects over 50 million people worldwide with limited therapeutic options. Despite evidence highlighting the vital role of local immune cells in regulating the life cycle of hair follicles (HFs), accurate regulation of immunocytes to directly promote hair growth remains unachieved. Here, inspired by the physiological feedback in the skin immunity to suppress microbe-triggered inflammation, we develop an oligosaccharide biomaterial with “unmasked” specific activity to recruit T reg cells around HFs, leading to accelerated hair growth in mice. By processing the glucomannan polysaccharide via controllable enzymatic cleavage, we obtain a series of oligosaccharide fractions with more specific chemokine-inducing functions. Notably, a hexasaccharide-based fraction (OG6) stimulates macrophages to selectively express T reg -chemoattractant CCL5 through a mannose receptor-mediated endocytosis and NOD1/2-dependent signaling, as evidenced by molecular docking, inhibition assays, and a Foxp3 -reporter mouse model. Intradermal delivery of OG6 to the depilated mouse skin promotes T reg mobilization around HFs and stimulates de novo regeneration of robust hairs. Our study demonstrates that unmasking precise immunomodulatory functions in oligosaccharides from their parental polysaccharide can potentially solve the long-lasting dilemma with polysaccharide biomaterials that are widely renowned for versatile activities yet high heterogeneity, opening new avenues to designing glycan-based therapeutic tools with improved specificity and safety. This article is protected by copyright. All rights reserved
研究领域:
免疫学
·
生物材料科学
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皮肤科
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FEBS Open Bio
·
2021
·Vol. 11
·期 5
·1395-1405
·
IF 2.693
Dan Wang,Zikun Zhang,Zekun Si,Yanlin Yang,Shuangshuang Li,Yaoming Xue
An imbalance between T helper 17 (Th17) and T regulatory (Treg) cell subsets contributes to the pathogenesis of diabetic kidney disease (DKD). However, the underlying regulatory mechanisms that cause this imbalance are unknown. Serum/glucocorticoid-regulated kinase 1 (SGK1) has been suggested to affect Th17 polarization in a salt-dependent manner, and sodium/glucose cotransporter 2 inhibitors (SGLT2i) have been demonstrated to regulate sodium-mediated transportation in the renal tubules. This study aimed to evaluate the potential benefits of dapagliflozin (Dap) on DKD, as well as its influence on shifting renal T-cell polarization and related cytokine secretion. We treated male db/db mice with Dap or voglibose (Vog) and measured blood and kidney levels of Th17 and Treg cells using flow cytometry. We found that Th17 cells were significantly increased, while Treg cells were significantly decreased in diabetic mice. Moreover, Dap suppressed the polarization of Th17/Treg cells by inhibiting SGK1 in diabetic kidneys, and this was accompanied by attenuation of albuminuria and tubulointerstitial fibrosis independent of glycemic control. Taken together, these results demonstrate that the imbalance of Th17/Treg cells plays an important role in the progression of DKD. Moreover, Dap protects against DKD by inhibiting SGK1 and reversing the T-cell imbalance.
研究领域:
药理学
·
免疫学
·
糖尿病学
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肾病学
✓ 已验证
DOI
PubMed
高影响因子
Nutrients
·
2024
·Vol. 16
·期 13
·2052
·
IF 4.8
Haidong Wang,Ji Qiu,Minyao Zhou,Yanqiu Luo,Xinyu Li,Minqi Wang
In this study, we investigated the effect of monobutyrin (MB) on the gut microbiota and intestinal health of weaned mice. MB was administered via gavage to 21-day-old weaned mice. Samples of small intestinal and ileal contents were collected on day 1, day 7, and day 21 post-administration. Seven days of MB administration enhanced the mucin layer and morphological structure of the intestine and the integrity of the intestinal brush border. Both MB and sodium butyrate (SB) accelerated tight junction development. Compared to SB, MB modulated intestinal T cells in a distinct manner. MB increased the ratio of Treg cells in the small intestine upon the cessation of weaning. After 21 days of MB administration, enhancement of the villus structure of the ileum was observed. MB increased the proportion of Th17 cells in the ileum. MB facilitated the transition of the small intestinal microbiota toward an adult microbial community structure and enhanced the complexity of the microbial community structure. An increase in Th17 cells enhanced intestinal barrier function. The regulatory effect of MB on Th17 cells may occur through the intestinal microbiota. Therefore, MB can potentially be used to promote intestinal barrier function, especially for weaning animals, with promising application prospects.
研究领域:
微生物学
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免疫学
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营养学
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动物科学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2021
·
IF 4.932
Jingjing Li,Suiyuan Ren,Meng Li,Jingai Bi,Guang Yang,Erguang Li
Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) that causes inflammation and ulcers in the digestive tract. The treatment commonly includes anti-inflammatory agents like 5-aminosalicylic acid or corticosteroids or biologics for people with UC who are no longer responding to corticosteroids. The radices of Paeonia lactiflora Pall. or similar plants of the Paeonia genus have been used in Chinese medicine to treat certain diseases that resemble the symptoms of UC. Paeoniflorin, a terpenoid glycoside, is a major active component for the anti-inflammatory and antitumor activity. In this study, we evaluated the therapeutic effect of paeoniflorin (PF) against dextran sulfate sodium (DSS)-induced colitis in mice and found that PF exhibited protective activity against colitis. PF treatment suppressed NF-κB pathway activation, resulting down regulation of pro-inflammatory factor expression. In addition, we detected reduction in eosinophil-related chemokine gene expression and eosinophil infiltration. The treatment also reversed Treg cell population suppression. Although PF treatment did not block COX2 induction, the compound weakly inhibited COX2 activity in an enzymatic assay. Taken together, PF exerts its therapeutic activity against UC through inhibition of inflammation and eosinophil infiltration.
研究领域:
药理学
·
免疫学
·
胃肠病学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Yue Cao,Shouchun Xiao,Bingying He,Xinlei Shi,Nan Xiao,Xueke Liu,Donghui Liu,Zhiqiang Zhou,Peng Wang
Fluxapyroxad is the most commonly used succinate dehydrogenase inhibitor fungicide. This work investigated its adverse effects on colitis susceptibility and explored the underlying mechanisms based on a mouse model. After 13 weeks of exposure at the acceptable daily intake (ADI) level, fluxapyroxad exacerbated the susceptibility to colitis, impaired the intestinal barrier, and elevated proinflammatory cytokines and chemokines of the colon in mice. It was found that this toxic effect was caused by the disruption of the gut microbiome. Specifically, the abundance of Lachnospiraceae and Muribaculaceae decreased, while Desulfovibrionaceae and Eggerthellaceae increased. Altered microbiota reduced fecal indole derivatives, including indole-3-lactic acid (ILA), indole-3-acetic acid (IAA), and indole-3-acrylic acid (IArA), inhibiting aryl hydrocarbon receptor (AHR) activation, disrupting immune homeostasis by overactivating Th17 cells and insufficient Treg cell differentiation, and causing mild colonic inflammation. Oral antibiotic-treated mice and fecal transfer experiments validated the pathway. Susceptibility to colitis induced by fluxapyroxad was not detected in the oral antibiotic-treated mice. Fecal transfer of the disordered gut microbiota caused by fluxapyroxad could aggravate the severity of colitis in recipient oral antibiotic-treated mice that did not receive fluxapyroxad exposure. In conclusion, chronic fluxapyroxad exposure at the ADI level exacerbated colitis via a gut microbiota–indole derivatives–Treg/Th17 cell balance axis, offering a new risk assessment perspective of fluxapyroxad.
研究领域:
毒理学
·
免疫学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INFLAMMATION
·
2019
·Vol. 42
·期 5
·1705-1718
·
IF 2.939
Chen Jing,Zhan Changsheng,Zhang Li,Zhang Ligang,Liu Yi,Zhang Yong,Du Hexi,Liang Chaozhao,Chen Xianguo
Treg cells are crucial for maintaining immune homeostasis in CP/CPPS, but the molecular mechanisms underlying the modulation of the function of Treg in CP/CPPS remain unclear. The main purpose of this study is to investigate the relationship between immunosuppressive function of Treg and the methylation level of Foxp3 promoter in experimental autoimmune prostatitis (EAP) mouse model. EAP model was induced by subcutaneous injecting prostate-steroid-binding protein (PSBP) and complete Freund’s adjuvant with NOD mice. Histological analysis revealed that EAP model was successfully induced. The expression of IFN-γ was increased, and TGF-β was decreased in the serum of EAP, respectively. The percentage of Tregs in splenic lymphocyte was increased in EAP. The suppressive ability of Tregs on Teffs was impaired in EAP. The methylation level of Foxp3 promoter was increased, and the expression of Foxp3 was decreased in EAP. By injection AZA which was DNA-methylation inhibitor into EAP mice, prostate inflammation was alleviated, expressions of TGF-β and Foxp3 were increased, and the suppressive function of Tregs was improved in vitro and in vivo . Thus, we concluded that aberrant increased methylation of Foxp3 promoter in Treg cells leads to the impaired suppressive function of Treg cells, exacerbating autoimmune inflammatory injury in EAP.
研究领域:
免疫学
·
分子生物学
·
自身免疫疾病
·
表观遗传学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Xiaoxue Cao,Zhaoran Wang,Yi Jiao,Wenya Diao,Qishun Geng,Lu Zhao,Zihan Wang,Xing Wang,Mengxiao Zhang,Jiahe Xu,Bailiang Wang,Tingting Deng,Cheng Xiao
Treg cell-based therapy has exhibited promising efficacy in combatting rheumatoid arthritis (RA). Dihydroartemisinin (DHA) exerts broad immunomodulatory effects across various diseases, with its recent spotlight on T-cell regulation in autoimmune conditions. The modulation of DHA on Treg cells and its therapeutic role in RA has yet to be fully elucidated. This study seeks to unveil the influence of DHA on Treg cells in RA and furnish innovative substantiation for the potential of DHA to ameliorate RA. To this end, we initially scrutinized the impact of DHA-modulated Treg cells on osteoclast (OC) formation in vitro using Treg cell-bone marrow-derived monocyte (BMM) coculture systems. Subsequently, employing the collagen-induced arthritis (CIA) rat model, we validated the efficacy of DHA and probed its influence on Treg cells in the spleen and popliteal lymph nodes (PLN). Finally, leveraging deep proteomic analysis with data-independent acquisition (DIA) and parallel accumulation-serial fragmentation (PASEF) technology, we found the alterations in the Treg cell proteome in PLN by proteomic analysis. Our findings indicate that DHA augmented suppressive Treg cells, thereby impeding OC formation in vitro. Consistently, DHA mitigated erosive joint destruction and osteoclastogenesis by replenishing splenic and joint-draining lymph node Treg cells in CIA rats. Notably, DHA induced alterations in the Treg cell proteome in PLN, manifesting distinct upregulation of alloantigen Col2a1 (Type II collagen alfa 1 chain) and CD8a (T-cell surface glycoprotein CD8 alpha chain) in Treg cells, signifying DHA's targeted modulation of Treg cells, rendering them more adept at sustaining immune tolerance and impeding bone erosion. These results unveil a novel facet of DHA in the treatment of RA.
研究领域:
免疫学
·
风湿病学
·
药理学
·
蛋白质组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2025
·
IF 12.1
Luoyingzi Xie,Jie Gong,Zhiqiang He,Weinan Zhang,Haoyu Wang,Shitao Wu,Xianxing Wang,Pijiang Sun,Lei Cai,Zhongjun Wu,Huaizhi Wang
Cancer is one of the most important challenges worldwide with an increasing incidence. However, most of patients with malignant cancer receiving traditional therapies have tumor recurrence and short-term 5-year survival. Herein, a novel Cu 2 O-MnO@PEG (CMP) nanomaterial is developed to treat tumors. CMP directly mediates cuproptosis in tumor cells. Meanwhile, CMP potentiates anti-tumor immune responses in the tumor microenvironment (TME) to induce tumor regression. CMP improves the tumor antigen processing and presentation of dendritic cells and tumor-associated macrophages, and further promotes CD8 + T cell responses, especially for cytotoxic CD8 + T cells and transitory exhausted CD8 + T cells. Additionally, CMP downregulates the proportion of Treg cells and CTLA-4 expression on Treg cells. Notably, CMP induces systemic immune responses against distant tumors and long-term immune memory. Furthermore, CMP synergized with PD-L1 mAb promotes tumor inhibition and sustains the anti-tumor efficacy post PD-L1 mAb treatment. Collectively, this strategy has the clinically therapeutic potential for tumors by facilitating cuproptosis in tumor cells and anti-tumor immune responses.
研究领域:
肿瘤学
·
免疫学
·
纳米医学
✓ 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）