Immunological Investigations最新文献_第2页

M1 Monocyte Polarization and Deficient Immunomodulation in Preeclampsia. 子痫前期M1单核细胞极化和免疫调节缺陷。

IF 2.4 4区医学

Immunological Investigations Pub Date : 2025-10-01 Epub Date: 2025-06-04 DOI: 10.1080/08820139.2025.2511081

Mariana Romao-Veiga, Amanda Carreira Devides, Vanessa Rocha Ribeiro-Vasques, Mariana Leticia Matias, Virginia Juliani Gomes, Graziela Gorete Romagnoli, Maria Terezinha Serrao Peraçoli, Jose Carlos Peraçoli

{"title":"M1 Monocyte Polarization and Deficient Immunomodulation in Preeclampsia.","authors":"Mariana Romao-Veiga, Amanda Carreira Devides, Vanessa Rocha Ribeiro-Vasques, Mariana Leticia Matias, Virginia Juliani Gomes, Graziela Gorete Romagnoli, Maria Terezinha Serrao Peraçoli, Jose Carlos Peraçoli","doi":"10.1080/08820139.2025.2511081","DOIUrl":"10.1080/08820139.2025.2511081","url":null,"abstract":"Introduction: Preeclampsia (PE) is a specific pregnancy syndrome characterized by a systemic inflammatory response that may be dependent on the presence of danger molecules called damage-associated molecular patterns (DAMPs). High mobility group Box 1 (HMGB1) is a DAMP that shows possible interaction with haptoglobin and can be removed from circulation by the CD163 receptor.Objective: This study aimed to evaluate the involvement of haptoglobin, HMGB1, and CD163 receptor in the systemic inflammatory response in pregnant women with PE.Methods: Monocytes obtained from preeclamptic and normotensive (NT) pregnant women were evaluated for surface TLR4, RAGE, CD64, and CD163 receptors, as well as intracellular haptoglobin and HMGB1 expression by flow cytometry.Results: Plasma levels of haptoglobin, HMGB1, and hemeoxygenase-1, as well as pro- and anti-inflammatory cytokines, were determined by the ELISA. Compared with NT group expression of TLR4, CD64, and RAGE receptors and intracellular HMGB1 and haptoglobin by monocytes was higher in women with PE, whereas extracellular CD163 expression was reduced in this group. Plasma concentrations of HMGB1, TNF-α, IL-1β, and IL-6 were higher in preeclamptic women, whereas the levels of haptoglobin, hemeoxygenase-1, and IL-10 were significantly lower.Conclusion: The elevated concentration of inflammatory cytokines and higher expression of TLR4, CD64, and RAGE receptors demonstrated that monocytes from PE women are polarized to the M1-like profile. Furthermore, the CD163 internalization and the absence of a high haptoglobin monocyte subset, along with decreased levels of haptoglobin, IL-10, and hemeoxygenase-1 in the PE group, indicates a deficiency in mechanisms that could regulate the intense inflammatory process associated with PE.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1081-1098"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Regulatory T Cells in Colon Cancer: Implications for Pathogenesis, Prognosis and Emerging Therapeutic Strategies. 调节性T细胞在结肠癌中的作用：发病机制、预后和新出现的治疗策略。

IF 2.4 4区医学

Immunological Investigations Pub Date : 2025-10-01 Epub Date: 2025-07-21 DOI: 10.1080/08820139.2025.2529970

Faris Anad Muhammad, Abdulkareem Shareef, S Renuka Jyothi, Sachin Kumar, Ashish Singh Chauhan, Apurav Gautam, Maksuda Ashurova, Hayder Naji Sameer, Ahmed Yaseen, Zainab H Athab, Mohaned Adil, Ayda Abrari, Mahyar Mohammadifard

{"title":"Regulatory T Cells in Colon Cancer: Implications for Pathogenesis, Prognosis and Emerging Therapeutic Strategies.","authors":"Faris Anad Muhammad, Abdulkareem Shareef, S Renuka Jyothi, Sachin Kumar, Ashish Singh Chauhan, Apurav Gautam, Maksuda Ashurova, Hayder Naji Sameer, Ahmed Yaseen, Zainab H Athab, Mohaned Adil, Ayda Abrari, Mahyar Mohammadifard","doi":"10.1080/08820139.2025.2529970","DOIUrl":"10.1080/08820139.2025.2529970","url":null,"abstract":"Introduction: Colon cancer is a highly heterogeneous malignancy with significant global incidence and mortality. The tumor microenvironment (TME) plays a pivotal role in disease progression and treatment response. Among key components of the TME are tumor-infiltrating lymphocytes (TILs), particularly regulatory T cells (Tregs) and effector T cells, whose balance influences cancer outcomes.Methods: This review analyzes recent findings regarding the role of Treg cells in colon cancer progression by evaluating preclinical and clinical studies that explore immune cell composition, function, and modulation within the TME.Results: Treg cells demonstrate a dual role in colon cancer. While they suppress effective anti-tumor immune responses, facilitating immune evasion, they may also mitigate chronic inflammation, which contributes to carcinogenesis. High intratumoral Treg levels are correlated with poor prognosis, reduced immunotherapy efficacy, and lower overall survival. Strategies to deplete or reprogram Tregs, such as immune checkpoint inhibition, modulation of T cell plasticity, and selective targeting, have shown promise in enhancing anti-tumor immunity.Discussion: Complete depletion of Tregs risks inducing autoimmune toxicity. Therefore, a precise understanding of Treg cell subsets and functions is essential. This review highlights the importance of developing targeted immunotherapeutic strategies that modulate Treg activity while preserving immune homeostasis in colon cancer treatment.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1012-1063"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Expression of the Transcription Factor FOXP3 in Human Peripheral Blood B-Cell Subtypes (CD19+CD39+ and CD19+CD39-) and Evaluation of Their Regulatory Function. 转录因子FOXP3在人外周血b细胞亚型（CD19+CD39+和CD19+CD39-）中的表达及其调控功能评价

IF 2.4 4区医学

Immunological Investigations Pub Date : 2025-10-01 Epub Date: 2025-06-11 DOI: 10.1080/08820139.2025.2515411

A Cardenas-Juarez, E E Uresti-Rivera, F Ochoa-González, F I Lira-Hernández, E E Lara-Ramírez, J M Vargas-Morales, B Rivas-Santiago, D P Portales-Peréz, M H García-Hernández

{"title":"Expression of the Transcription Factor FOXP3 in Human Peripheral Blood B-Cell Subtypes (CD19+CD39+ and CD19+CD39-) and Evaluation of Their Regulatory Function.","authors":"A Cardenas-Juarez, E E Uresti-Rivera, F Ochoa-González, F I Lira-Hernández, E E Lara-Ramírez, J M Vargas-Morales, B Rivas-Santiago, D P Portales-Peréz, M H García-Hernández","doi":"10.1080/08820139.2025.2515411","DOIUrl":"10.1080/08820139.2025.2515411","url":null,"abstract":"Introduction: The aim of this study was to evaluate FOXP3 expression in CD19+CD39+ and CD19+CD39- B cells, and to investigate its potential regulatory role.Methods: Peripheral B cells were obtained from 25 volunteers. FOXP3 expression at the mRNA and protein levels was analyzed in CD19+CD39+ and CD19+CD39- B cells by FACS and RT-qPCR. Suppressive activity was assessed through co-cultures of PBMC with CD19+CD39+ and CD19+CD39- B cells stimulated with anti-CD3/CD28, evaluating T cell proliferation and the percentage of Th1 cells.Results: The percentage of CD19+CD39+ FOXP3+ B cells was higher compared to other phenotypes. There was a positive correlation between FOXP3 and CD39 in CD19+ B cells. FOXP3 mRNA was increased in CD19+CD39+ B cells compared to CD19+CD39- B cells. CD19+CD39- B cells reduced the proliferation, the percentage of Th1 cells, and expressed higher IL-10 mRNA compared to CD19+CD39+ B cells. B cell phenotypes were inversely associated with Th1 cells and CRP. CD19+CD39- was associated with HOMA-β. CD19+CD39+ was inversely associated with HbA1c.Discussion: FOXP3 is expressed on both CD19+CD39- and CD19+CD39+ B lymphocytes. CD19+CD39- cells showed high levels of IL-10 and low levels of FOXP3 mRNA. CD19+CD39- B cells decreased the Th1 cells and were associated with β-cell function.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1110-1125"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Indoleamine 2,3-Dioxygenase and Tryptophan Catabolism: Key Players in Immunosuppression and Intracellular Parasite Survival Mechanisms. 吲哚胺2,3-双加氧酶和色氨酸分解代谢：免疫抑制和细胞内寄生虫生存机制的关键参与者。

IF 2.4 4区医学

Immunological Investigations Pub Date : 2025-10-01 Epub Date: 2025-05-30 DOI: 10.1080/08820139.2025.2511079

Lisset Torres-Martínez, Abraham U Morales-Primo, Jaime Zamora-Chimal

{"title":"Indoleamine 2,3-Dioxygenase and Tryptophan Catabolism: Key Players in Immunosuppression and Intracellular Parasite Survival Mechanisms.","authors":"Lisset Torres-Martínez, Abraham U Morales-Primo, Jaime Zamora-Chimal","doi":"10.1080/08820139.2025.2511079","DOIUrl":"10.1080/08820139.2025.2511079","url":null,"abstract":"Background: Indoleamine 2,3-dioxygenase (IDO) is a heme enzyme that catalyzes the oxidative degradation of L-tryptophan (L-Trp) through the kynurenine pathway (KP), generating metabolites that regulate immune responses. These byproducts, mainly kynurenines, contribute to immunosuppression and influence immune cell differentiation, promoting regulatory T cells (Tregs) and inducing apoptosis in inflammatory cells.Methods: We conducted a comprehensive literature review to examine the roles of IDO and KP metabolites in intracellular parasitic infections. Our analysis focused on studies involving Leishmania, Trypanosoma cruzi, Toxoplasma gondii, and Plasmodium species.Results: IDO has a dual role in parasitic diseases: L-Trp depletion can inhibit parasite growth, but also promotes an immunosuppressive microenvironment that may facilitate pathogen persistence. This balance between host defense and immune evasion is crucial in chronic infections. We discuss how IDO activity intersects with parasite immune evasion strategies and review potential therapeutic approaches targeting the IDO-KP axis.Conclusion: IDO plays a complex and context-dependent role in the immunopathology of intracellular parasitic infections. While it may support host defense, its immunoregulatory effects can also favor chronic infection. Therapeutically targeting the IDO pathway is a promising strategy, but requires further investigation to optimize its clinical application.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"909-934"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DNA methylation and transcriptome signatures of the FOXO1 gene in ankylosing spondylitis. 强直性脊柱炎FOXO1基因的DNA甲基化和转录组特征。

IF 2.4 4区医学

Immunological Investigations Pub Date : 2025-10-01 Epub Date: 2025-06-17 DOI: 10.1080/08820139.2025.2517814

Xiaohan Jing, Li Fan, Yuan Wang, Yuchen Zhang, Tongbin Xue, Di Tian, Feilong Zhang, Yuting Chen, Baoming Wu, Ye Wu

{"title":"DNA methylation and transcriptome signatures of the FOXO1 gene in ankylosing spondylitis.","authors":"Xiaohan Jing, Li Fan, Yuan Wang, Yuchen Zhang, Tongbin Xue, Di Tian, Feilong Zhang, Yuting Chen, Baoming Wu, Ye Wu","doi":"10.1080/08820139.2025.2517814","DOIUrl":"10.1080/08820139.2025.2517814","url":null,"abstract":"Background: Ankylosing spondylitis (AS) is an inflammatory autoimmune disease with complex etiology. The forkhead box O (FOXO) 1 is an important transcription factor related to proliferation, homeostasis and metabolism. Notably, the involvement of methylation and the expression of mRNA in the promoter region of the FOXO1 gene in relation to AS is still not understood.Methods: A two-stage case-control study enrolled 60 AS patients and 60 healthy controls (HCs) for integrated demographic and clinical evaluation and DNA methylation profiling. Subsequently, FOXO1 mRNA expression was comparatively assessed in 30 AS patients and 30 hCs.Results: The methylation levels of 2 islands and 10 sites in the promoter region of FOXO1 gene were significantly different between AS patients and healthy controls. The negative correlation between the mRNA expression and the methylation level of FOXO1 gene was revealed (rs = -0.624, p < .001). Subgroup analyses showed that male and HLA-B27(+) having high methylation level in AS patients (p = .008; p = .036). Moreover, the level of hypermethylation was positively correlated with the clinical features like ASDAS, and negatively correlated with LYM, MON, RDW and disease duration.Conclusion: DNA methylation and transcription of FOXO1 might be related to AS susceptibility and play an important role in the etiology of AS.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1152-1166"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Recombinant Protein UBC13 Improves Tissue Injury of MRL/Lpr Mice by Alleviating Th1/Th2 Immune Imbalance. 重组蛋白UBC13通过缓解Th1/Th2免疫失衡改善MRL/Lpr小鼠组织损伤

IF 2.4 4区医学

Immunological Investigations Pub Date : 2025-10-01 Epub Date: 2025-05-30 DOI: 10.1080/08820139.2025.2509086

Mengchen Qi, Qian Li, Bingyao Ren, Ling Guo, Likang Zhang, Yulong Yang, Jiali Tao, Bin Sun, Junbing Jiang

{"title":"Recombinant Protein UBC13 Improves Tissue Injury of MRL/Lpr Mice by Alleviating Th1/Th2 Immune Imbalance.","authors":"Mengchen Qi, Qian Li, Bingyao Ren, Ling Guo, Likang Zhang, Yulong Yang, Jiali Tao, Bin Sun, Junbing Jiang","doi":"10.1080/08820139.2025.2509086","DOIUrl":"10.1080/08820139.2025.2509086","url":null,"abstract":"Objectives: This study aimed to investigate the role of T-cell imbalance in the pathogenesis of systemic lupus erythematosus (SLE), the role of Ubiquitin-binding enzyme 2N (UBC13) in the treatment of SLE.Methods: Mice in the model group were intraperitoneally injected with normal saline. The UBC13 group was administered UBC13 recombinant protein, and the dexamethasone (DXM) group was treated with DXM for 8 weeks. Serum anti-dsDNA and ANA levels were quantified via ELISA. Histopathological changes were analyzed using H&E staining. Splenic mRNA expression of inflammatory cytokines and transcription factors was analyzed using qRT-PCR. Flow cytometry was used characterize Th1, Th2 and Treg cells populations, while western blotting was used to detect STAT3 and NF-κB signalling pathway-related proteins in thymic lysates.Results: UBC13 administration ameliorated splenic hyperplasia and attenuated tissue damage in MRL/lpr mice, accompanied by a reduction in serum anti-dsDNA and ANA titers. Proinflammatory cytokine production, was suppressed following UBC13 intervention. Concurrently, UBC13 restored Th1/Th2 cell equilibrium and enhanced Treg cell suppressive function. Mechanistically, UBC13 inhibited NF-κB pathway activation and suppressed STAT3 phosphorylation.Conclusion: UBC13 restores the homeostasis and function of Th1/Th2 and Treg cell through suppression of STAT3 and the NF-κB signaling pathway activation, thereby mitigating SLE-induced organ damage.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1064-1080"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Role of the Immune Microenvironment on Osteoblast Differentiation. 免疫微环境在成骨细胞分化中的作用。

IF 2.4 4区医学

Immunological Investigations Pub Date : 2025-10-01 Epub Date: 2025-07-14 DOI: 10.1080/08820139.2025.2527246

Mengtao Wang, Zhicheng Cao, Wenhui Hu, Zhiwen Dong, Yufeng Wang, Changyan Ma, Cheng Tang

{"title":"The Role of the Immune Microenvironment on Osteoblast Differentiation.","authors":"Mengtao Wang, Zhicheng Cao, Wenhui Hu, Zhiwen Dong, Yufeng Wang, Changyan Ma, Cheng Tang","doi":"10.1080/08820139.2025.2527246","DOIUrl":"10.1080/08820139.2025.2527246","url":null,"abstract":"Background: Osteoblasts, derived from mesenchymal stem cells (MSCs) in the bone marrow, are responsible for bone formation. Osteoblast differentiation is orchestrated by a spectrum of biological signals, with immune-derived components serving as indispensable regulators in this network. Dysfunctional osteoblast differentiation underlies bone-related pathologies such as osteoarthritis, rheumatoid arthritis, and osteoporosis, where immune dysregulation drives inflammatory cascades that disrupt the osteoblast-osteoclast equilibrium. This bidirectional crosstalk has propelled the emergence of osteoimmunology as a pivotal discipline.Methods: By analyzing immune cells and cytokines in the immune microenvironment, we synthesize evidence on their roles in regulating osteoblast differentiation, with focus on inflammatory bone disorders, particularly in osteoarthritis.Results: Thus, bone growth, development, and healing are intrinsically coupled with the dynamics of the immune microenvironment, which contributes to subchondral bone sclerosis and disease progression in osteoarthritis. Therefore, targeting immune-osteoblast crosstalk offers therapeutic potential for bone pathologies.Conclusion: This review consolidates recent advances in understanding how the immune microenvironment impacts osteoblast differentiation, aiming to provide novel insights for clinical strategies targeting bone repair and disease mitigation.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"962-1011"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

T Cells Expressing Ras Homolog Family Member a Display Enhanced Cytotoxicity but are Reduced in Lupus Peripheral Blood. 表达Ras同源家族成员a的T细胞在狼疮外周血中显示增强的细胞毒性但降低。

IF 2.4 4区医学

Immunological Investigations Pub Date : 2025-10-01 Epub Date: 2025-06-19 DOI: 10.1080/08820139.2025.2517364

Ziqi Xiong, Zhao Guan, Ainizati Hasimu, He Yu, Sen Zhou, Ayibaota Bahabayi, Qi Li, Guochong Wang, Zhonghui Zhang, Rui Kang, Pingzhang Wang, Chen Liu

{"title":"T Cells Expressing Ras Homolog Family Member a Display Enhanced Cytotoxicity but are Reduced in Lupus Peripheral Blood.","authors":"Ziqi Xiong, Zhao Guan, Ainizati Hasimu, He Yu, Sen Zhou, Ayibaota Bahabayi, Qi Li, Guochong Wang, Zhonghui Zhang, Rui Kang, Pingzhang Wang, Chen Liu","doi":"10.1080/08820139.2025.2517364","DOIUrl":"10.1080/08820139.2025.2517364","url":null,"abstract":"Objective: This study aimed to explore the expression and clinical relevance of Ras homolog family member A (RhoA) in T cell subsets from patients with systemic lupus erythematosus (SLE).Methods: Peripheral blood samples were obtained from newly diagnosed SLE patients and age- and sex-matched healthy controls. T cell subpopulations were analyzed by flow cytometry to quantify RhoA levels and associated cytotoxic markers, including granzyme B (GrB) and perforin (PFFN). Publicly available single-cell RNA sequencing (scRNA-seq) data were used to validate RhoA transcriptional patterns. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis.Results: RhoA was unevenly distributed among circulating T cell populations, with the highest protein expression observed in CD8+ and effector memory subsets. RhoA+ T cells showed significantly higher GrB and PFN levels compared to their RhoA+ counterparts. In early-stage SLE, RhoA expression in T cells was significantly reduced compared to healthy individuals. However, a greater proportion of CD8+RhoA+ cells expressed GZMB in SLE patients. ROC analysis yielded area under the curve (AUC) values of 0.6720 for CD4+RhoA+ and 0.6635 for CD8+RhoA+ T cells.Conclusion: RhoA+ T lymphocytes exhibit enhanced cytotoxic potential and may serve as early immunological markers for the identification of SLE.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1138-1151"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of Sapropterin against Non-Alcoholic Fatty Liver Disease in mice. 沙普霉素对小鼠非酒精性脂肪肝的作用。

IF 2.4 4区医学

Immunological Investigations Pub Date : 2025-10-01 DOI: 10.1080/08820139.2025.2565735

Jie Jiang, Zongqiang Hu, Li Li

{"title":"Effects of Sapropterin against Non-Alcoholic Fatty Liver Disease in mice.","authors":"Jie Jiang, Zongqiang Hu, Li Li","doi":"10.1080/08820139.2025.2565735","DOIUrl":"https://doi.org/10.1080/08820139.2025.2565735","url":null,"abstract":"Background: Tetrahydrobiopterin (BH₄) maintains nitric oxide synthase (NOS) coupling. However, its therapeutic potential in non-alcoholic fatty liver disease (NAFLD) remains unexplored.Methods: Male C57BL/6J mice were subjected to a high-fat diet (HFD) for 16 weeks to establish NAFLD, with oral administration of sapropterin (10 mg/kg/day) initiated at week 5.Results: Sapropterin treatment significantly elevated both systemic and hepatic BH₄ concentrations and ameliorated HFD-induced dyslipidemia, as evidenced by reductions in circulating total cholesterol, triglycerides, and low-density lipoprotein cholesterol. Hepatocellular injury markers (ALT, AST) were also markedly decreased. Histopathological examination revealed substantial improvements in hepatic steatosis, ballooning degeneration, and macrovesicular lipid accumulation, with the NAFLD activity score reduced by 63.1% and hepatic lipid content by over 60%. Molecular analyses demonstrated that sapropterin suppressed lipogenic gene expression (Fasn, Cd36) and enhanced transcription of Ppara, promoting lipid catabolism. Concurrently, hepatic fibrotic burden was significantly reduced, accompanied by downregulation of Tgfb1 and diminished TGF-β protein expression. Anti-inflammatory effects were evidenced by decreased hepatic IL-6 and IL-1β levels and a 131.5% increase in IL-10. Additionally, sapropterin facilitated macrophage polarization toward an anti-inflammatory M2 phenotype (Cd206, Arg1), while suppressing pro-inflammatory M1 markers (Cd86).Conclusion: These findings indicated that sapropterin improvedNAFLD by regulatinglipid metabolism, inflammation, and fibrosis.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1-19"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetic Differences Between N and J Sub-Strains of C57BL/6 Mice Critically Affect Multiple Immune Responses and Their Microbiota. C57BL/6小鼠N亚株和J亚株的遗传差异严重影响多种免疫反应及其微生物群

IF 2.4 4区医学

Immunological Investigations Pub Date : 2025-10-01 Epub Date: 2025-06-26 DOI: 10.1080/08820139.2025.2523315

Andreas Hiergeist, Sarah Miksch, Nicole Sabouret, Michaela Seeling, Katja Hohenberger, Joachim Gläsner, Falk Nimmerjahn, Markus Biburger, André Gessner

{"title":"Genetic Differences Between N and J Sub-Strains of C57BL/6 Mice Critically Affect Multiple Immune Responses and Their Microbiota.","authors":"Andreas Hiergeist, Sarah Miksch, Nicole Sabouret, Michaela Seeling, Katja Hohenberger, Joachim Gläsner, Falk Nimmerjahn, Markus Biburger, André Gessner","doi":"10.1080/08820139.2025.2523315","DOIUrl":"10.1080/08820139.2025.2523315","url":null,"abstract":"Background: Within decades of breeding, the common laboratory mouse strain C57BL/6 (B6) divided into various sub-strains with B6J and B6N being most frequently used. Recent studies showed significant genetic differences affecting several physiological, biochemical, and behavioral properties. In the immunology field, however, differences between these strains have barely been characterized and the necessity to use the adequate B6 sub-strain as experimental control appears largely unrecognized.Methods: B6J and B6N mice were tested for a potential impact of their genetic background in various immunological models including experimental antibody-mediated immune-thrombocytopenia (ITP), B-cell depletion, K/BxN arthritis model, models of acute pneumonia, and dextran sulfate sodium (DSS)-induced colitis. Additionally, gut microbiota composition was analyzed in both healthy animals and in the context of DSS colitis.Results: B6J and B6N mice performed equally in experimental antibody-mediated immune-thrombocytopenia and B-cell depletion. However, they revealed pronounced differences in the K/BxN arthritis model as well as in models of acute pneumonia and DSS-induced colitis. Furthermore, the B6 sub-strains demonstrated remarkable differences in gut microbiota composition that were detectable already in healthy animals and became augmented in the context of DSS colitis.Conclusion: These findings mandate that researchers must specify and match B6 sub-strain backgrounds in immunological studies to ensure reproducibility and avoid misinterpretation of genetic modifications' effects.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1167-1194"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144496102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0