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Treg/Th17
Antioxidants · 2025 ·Vol. 14 ·期 4 ·468 · IF 6.6

Selenium-Binding Protein 1-Deficient Dendritic Cells Protect Mice from Sepsis by Increased Treg/Th17

Xin Zhang,Shuang Han,Zhu Zeng,Jie Dai,Yi Jia

Selenium-binding protein 1 (SELENBP1) has been implicated in cancer development, neurological disorders, tissue injury, metabolic regulation, and cell differentiation. Sepsis is characterized prominently by immunological dysregulation and severe organ damage. However, whether SELENBP1 improves sepsis by regulating immune cell activity remains unknown. Here, we detected an elevation of SELENBP1 levels in the blood of sepsis patients and in the livers of septic mice. Significantly, SELENBP1 knockout (KO) prolonged survival in septic mice. This phenomenon was accompanied by decreased liver damage, reduced inflammation levels, and an increased regulatory T cell/T helper 17 cell (Treg/Th17) ratio in the spleen. Additionally, SELENBP1 deficiency induced a redox imbalance and inhibited dendritic cell (DC) maturation, resulting in a tolerogenic DC (tolDC) phenotype and an increase in the Treg/Th17 ratio. Furthermore, SELENBP1-KO mature DCs (mDCs) alleviated liver injury by increasing the Treg/Th17 ratio in the spleen, thus improving the survival of septic mice. These findings indicate that SELENBP1 is involved in sepsis by regulating DC immune activity, which might provide a potential way for sepsis treatment.

研究领域: 免疫学 · 医学
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2024 · IF 5.7

Litchi Procyanidins Ameliorate DSS-Induced Colitis through Gut Microbiota-Dependent Regulation of Treg/Th17 Balance

Benyue Sun,Yunhui Wang,Jingjing Bai,Xuejiao Li,Long Ma,Shuli Man

Ulcerative colitis (UC) is a common chronic, relapsing inflammatory bowel condition. Procyanidins (PC) are known for their antiangiogenic, anti-inflammatory, antioxidant, and antimetastatic properties. However, there is comparatively limited information on how PC interacts with UC. In this study, 5 mg/10 mL/kg body weight of PC was administered to mice with dextran sulfate sodium (DSS)-induced colitis mice. PC treatment prolonged the survival period of mice, ameliorated UC symptoms, reduced damage to the intestinal mucosal barrier, and increased the protein expression of ZO-1 and occludin in the DSS-treated mice. Importantly, PC treatment significantly reduced gene expression related to Th17 cell differentiation, including STAT3, SMAD3, TGF-β, and JAK1. The results of the flow cytometry analysis indicated significant increase in the number of Treg cells and a concomitant decrease in the proportion of Th17 cells in the colon following PC treatment. Additionally, PC increased the abundance of gut microbiota such as Bacteroidota, Oscillospiraceae, Muribaculaceae, and Desulfovibrionaceae, as well as the concentrations of acetate acid, propionate acid, and butyrate acid in the feces. PC also activated short-chain fatty acid receptors, such as G-protein coupled receptor 43 in the colon, which promoted the proliferation of Treg cells. The depletion of gut microbiota and subsequent transplantation of fecal microbiota demonstrated that PC’s effects on gut microbiota were effective in improving UC and restoring intestinal Th17/Treg homeostasis in a microbiota-dependent manner. This suggests that PC could be a promising functional food for the prevention and treatment of UC in the future.

研究领域: 免疫学 · 胃肠病学 · 微生物学 · 药理学 · 营养学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Acta Pharmaceutica Sinica B · 2025 · IF 14.6

An anti-complement homogeneous polysaccharide from Houttuynia cordata ameliorates acute pneumonia with H1N1 and MRSA coinfection through rectifying Treg/Th17 imbalance in the gut–lung axis and NLRP3 inflammasome activation

Xinxing Li,Wenxin Ding,Yan Lu,Haiyan Zhu,Weilian Bao,Yang Liu,Jiaren Lyu,Lishuang Zhou,Hong Li,Jiyang Li,Daofeng Chen

The coinfection of respiratory viruses and bacteria is a major cause of morbidity and mortality worldwide, despite the development of vaccines and powerful antibiotics. As a macromolecule that is difficult to absorb in the gastrointestinal tract, a homogeneous polysaccharide from Houttuynia cordata (HCPM) has been reported to exhibit anti-complement properties and alleviate influenza A virus (H1N1)-induced lung injury; however, the effects of HCPM without in vitro antiviral and antibacterial activities on more complicated pulmonary diseases resulting from viral-bacterial coinfection remains unclear. This study established a representative coinfection murine pneumonia model infected with H1N1 (0.2 LD 50 ) and methicillin-resistant Staphylococcus aureus (MRSA, 10 7 CFU). HCPM significantly improved survival rate and weight loss, and ameliorated gut–lung damage and inflammatory cytokine production. Interestingly, the therapeutic effect of HCPM on intestinal damage preceded that in the lungs. Mechanistically, HCPM inhibited the overactivation of the intestinal complement (C3a and C5a) and suppressed the activation of the NLR family pyrin domain-containing 3 (NLRP3) pathway, which contributes to the regulation of the Treg/Th17 cell balance in the gut–lung axis. The results indicate the beneficial effects of an anti-complement polysaccharide against viral–bacterial coinfection pneumonia by modulating crosstalk between multiple immune regulatory networks.

研究领域: 免疫学 · 微生物学 · 药理学 · 呼吸医学
✓ 已验证 DOI PubMed 高影响因子
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EXPERIMENTAL ANIMALS · 2023 · IF 2.4

Oroxylin A inhibited autoimmune hepatitis-induced liver injury and shifted Treg/Th17 balance to Treg differentiation

Jinxia ZHU,Hongxiu CHEN,Jianjiao CUI,Xiaorui ZHANG,Guangwei LIU

Autoimmune hepatitis (AIH) is a kind of autoimmune disease mediated by T cells, and its incidence is gradually increasing in the world. Oroxylin A (OA) is one of the major bioactive flavonoids that has been reported to inhibit inflammatory. Here, an AIH model of mouse was induced by Concanavalin A (Con A). It found that serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were decreased in mice with the treatment of OA. Hematoxylin-eosin staining showed that the liver injury was attenuated by OA, and TUNEL staining indicated that the cells apoptosis of liver was weakened in mice with OA treatment. ELISA analysis of cytokines and chemokines suggested that OA reduced the expression of IL-6, IL-17A, CCL2, CXCL1 and CXCL10, but promoted the expression of IL-10 and TGF-β in mice. The mRNA levels of IL-17A in liver and spleen tissues were also significantly decreased, on the contrary, the mRNA levels of IL-10 in liver and spleen tissues were increased. The proportion of Treg/Th17 detected by flow cytometry revealed that OA promoted the differentiation of Treg and inhibited the differentiation of Th17 both in the liver and spleen. The results of this study demonstrated the inhibitory effects of OA on AIH-induced liver injury and the inflammatory response of AIH, and revealed that OA affected the balance of Treg/Th17 and shifted the balance toward Treg differentiation. It provided new potential drugs for the prevention of AIH.

CAS / MDL: 11028-71-0
研究领域: 免疫学 · 药理学 · 肝病学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ENT-EAR NOSE & THROAT JOURNAL · 2021 · IF 1.697

Baicalin Ameliorates Inflammatory Response in a Mouse Model of Rhinosinusitis via Regulating the Treg/Th17 Balance

Ming Yang,Xiaoyan Zhu,Feida Fu,Qinghua Guo,Xiaopu Zhu,Yang Xu,Xiaotian Yan,Xinya He,Xu Wang

Objective:Rhinosinusitis is a global health problem affecting millions of people around the world. Baicalin is a bioactive compound isolated from medicinal plant Scutellaria baicalensis Georgi. The present study aims to investigate potential effects of baicalin on clinicopathological changes in nasal/sinus mucosa in a mouse model.Methods:A mouse model of sinonasal inflammation induced by high dose of ovalbumin was applied to evaluate effects of baicalin. Rhinosinusitis symptoms, histopathological features, levels of histamine, immunoglobulin E (IgE), IL-17A, IL-10, and balance of regulatory T cell (Treg)/T-helper 17 (Th17) responses were examined.Results:Baicalin significantly relieved rhinosinusitis symptoms in mice, reduced histopathological changes, and suppressed serum levels of histamine and IgE in a dose-dependent manner. In lymphocytes of mice, baicalin modulated balance of Treg/Th17 proportions by attenuating Th17 cells and enhancing Treg cells, respectively. The serum IL-17A was decreased and IL-10 was increased in mice treated by baicalin. In addition, baicalin promoted levels of Smad protein 3 (p-Smad3) and forkhead box P3 (FOXP3) to promote Treg cells while suppressed levels of p-Stat3 and retineic-acid-receptor-related orphan nuclear receptor γt (RORγt) to inhibit Th17 cells.Conclusions:These data demonstrate that baicalin effectively ameliorates sinonasal inflammation in a mouse model by recovering the immunological balance of Treg/Th17 responses. Our finding highlights the potential value of baicalin for the treatment of rhinosinusitis.

CAS / MDL: 21967-41-9
研究领域: 免疫学 · 药理学 · 病理学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

A bioinspired biotin-avidin hydrogel with prolonged SHED Exo delivery enhances diabetic wound healing by modulating the Treg/Th17 balance

Kunyao Guo,Qianyao Yu,Kaixi Zhu,Yuhui Yang,Tao Chen,Yiping Huang,Weiran Li

Stem cell-derived exosomes from human exfoliated deciduous Teeth (SHED-Exos) show promising treatment effects through immune modulation and angiogenic properties. However, when applied to diabetic wound healing, their inactivation and rapid clearance limit their clinical application. In this study, we aimed to develop a chitosan/dextran-based hydrogel using a biotin-avidin system that showed excellent injectability, adhesiveness, and antibacterial effects and enabled the slow and steady release of SHED-Exos to enhance diabetic wound healing. SHED-Exos were immobilized within a hydrogel through the biotin-avidin interaction and electrostatic forces of chitosan, allowing for slow release over >7 days. Additionally, the hydrogel exhibited excellent cell compatibility and supported cell spheroid growth in a 3D network. In vivo , the hydrogel significantly enhanced wound healing in diabetic rats by reducing inflammation and decreasing the ratio of Th17/Treg cells around wounds. This innovative noncellular hydrogel shows promise in facilitating the healing of diabetic wounds and may serve as a potential clinical therapy using natural bioactive materials delivery of exosomes.

✓ 已验证 产品关联 DOI 高影响因子
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MOLECULAR IMMUNOLOGY · 2023 · IF 3.6

SMURF1 inhibits the Th17 and Th17.1 polarization and improves the Treg/Th17 imbalance in systemic lupus erythematosus through the ubiquitination of RORγt

Wei Zhong,Leheng Feng,Wei Tian,Hongbo Qu,Haibo Xu,Ke Ning,Li Liu,Wei Liu,Xiaowei Gong,Hong Chen

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease . This study aimed to investigate the role of SMAD specific E3 ubiquitin protein ligase 1 (SMURF1) in the Th17 and Th17.1 differentiation and Treg/Th17 imbalance, which are major factors contributing to the pathogenesis of SLE. SLE patients and healthy individuals were recruited to detect the SMURF1 levels in naïve CD4 + cells from peripheral blood. Purified and expanded naïve CD4 + T cells were employed to evaluate the effects of SMURF1 on Th17 and Th17.1 polarization in vitro. MRL/lpr lupus model was employed to explore the disease phenotype as well as Treg/Th17 balance in vivo. The results showed that SMURF1 was down-regulated in naïve CD4 + T cells in peripheral blood of patients with SLE and in spleen of MRL/lpr mice. SMURF1 overexpression suppressed the polarization of naïve CD4 + T cells toward Th17 and Th17.1 phenotype and down-regulated the expression of retinoid-related orphan receptor-gammat (RORγt). Subsequently, SMURF1 down-regulation aggravated the disease phenotype, inflammation, and the Treg/Th17 imbalance in MRL/lpr mice. Furthermore, we found that SMURF overexpression promoted the ubiquitination and decreases the stability of RORγt. In conclusion, SMURF1 inhibited the polarization of Th17 and Th17.1 cells and improved the Treg/Th17 imbalance in SLE, which was mediated as least partly by the ubiquitination of RORγt.

CAS / MDL: 56092-81-0 16561-29-8
研究领域: 免疫学 · 自身免疫性疾病 · 分子生物学 · 细胞生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2023 · IF 8.2

Non-covalent binding of whey protein isolate after ultrasound pretreatment to epigallocatechin gallate: Effects on immune response and gut microbiota in BALB/c mice

Yueyue Meng,Huiyu Zhu,Lingyu Han,Zhe Xu,Yu Zou,Kun Ma,Tingting Li

Cow's milk is one of the “big eight” most common allergenic foods, and β-lactoglobulin and α-Lactalbumin in whey protein are two major allergens of cow's milk protein. An effective strategy for reducing the allergenicity of whey protein is needed. In the present study, protein-EGCG complexes were obtained through non-covalent interactions between untreated or sonicated whey protein isolate (WPI) and epigallocatechin gallate (EGCG), and the allergenicity of complexes was assessed in vivo. The results showed that SWPI-EGCG complex possesses low allergenicity in BALB/c mice. As compared with untreated WPI, SWPI-EGCG complex had less effect on the body weight and organ indexes. Moreover, SWPI-EGCG complex could alleviate the WPI induced allergic reactions and intestinal damage of mice by decreasing the secretion of IgE, IgG, histamine, mMCP-1, modulating the balance of Th1/Th2 and Treg/Th17 response, and increasing the diversity of intestinal flora and the relative abundances of probiotic bacteria. These findings indicate that the interaction of sonicated WPI with EGCG could reduce the allergenicity of WPI, which could provide a new strategy for reducing food allergenicity.

CAS / MDL: 989-51-5
研究领域: 食品科学 · 免疫学 · 微生物学 · 营养学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2018 · IF 3.909

Protective properties of combined fungal polysaccharides from Cordyceps sinensis and Ganoderma atrum on colon immune dysfunction

Song-Tao Fan,Shao-Ping Nie,Xiao-Jun Huang,Sunan Wang,Jie-Lun Hu,Jun-Hua Xie,Qi-Xing Nie,Ming-Yong Xie

In vivo an ecological network of polysaccharides utilization by gut microbiota is not only an intense competition but also an impressive cooperation pattern. The present study evaluated the in vivo protective effect of combined fungal polysaccharides (CFP) from Cordyceps sinensis and Ganoderma atrum on colon immune dysfunction, induced by 150   mg/kg cyclophosphamide (CP). The results showed that C. sinensis polysaccharides (CSP) significantly promoted microbial-derived butyrate to improve histone h3 acetylation mediating regulatory T (Treg) cell specific Foxp3, as well as significantly restored CP-induced elevation of interleukin (IL)-17 and IL-21. Additionally, G. atrum polysaccharides (PSG) significantly down-regulated MyD88, as well as significantly increased IL-10 and TGF-β3. Furthermore, CFP balanced the disequilibrium of cytokines secretion and Foxp3/RORγt ratio related Treg/T helper 17 (Th17) balance, as well as down-regulated the TLR-mediated inflammatory signaling pathway and promoted secretory immunoglobulin A (sIgA) secretion to suppress colonic inflammation. Therefore, our results typically contribute to understand the in vivo immunoregulatory function of fungal polysaccharides compounds, involving microbial-associated inflammatory signals and specific metabolic products.

研究领域: 免疫学 · 药理学 · 微生物学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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