Journal of Inflammation Research
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2025
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IF 4.1
Yuan Zhang,Longbin Huang,Ningning Yue,Zhiliang Mai,Chen Kong,Chengmei Tian,Dao-ru Wei,Jun Yao,Lisheng Wang,Defeng Li
Background Although cytokines have been implicated in the development of ulcerative colitis (UC), the potential mediating role of metabolite levels in this association remains unclear.Methods Utilizing data from genome-wide association studies (GWAS) encompassing 91 circulating cytokines, 1400 blood metabolites, and 178,689 UC cases, we performed a two-sample Mendelian randomization (MR) analysis to investigate the effect of metabolites mediated cytokines on the development of UC. A two-step MR analysis was conducted to quantitatively evaluate the mediation effect. Additionally, dextran sodium sulfate (DSS)-induced colitis mice were used to further confirm our results.Results Mendelian randomization (MR) analysis indicated that macrophage colony-stimulating factor (M-CSF) had a causal and positive relationship with aconitate (OR: 1.10, 95% CI: 1.00–1.20, p = 0.043, IVW beta 1 = 0.095). Moreover, MR analysis revealed that high level of aconitate were associated with reduced risk of UC (OR: 0.44, 95% CI: 0.24–0.80, p = 0.008, IVW beta 2 = −0.818). In addition, MR analysis showed M-CSF had an inverse correlation with the disease onset of UC (OR: 0.31, 95% CI: 0.15–0.80, p = 0.002, IVW beta all = −1.16). Furthermore, the mediation effect of aconitate mediated M-CSF on the risk of UC was −0.0777 (95% CI: −0.154 to −0.0018, p = 0.045), accounting for 6.69% of the total effect, and indicating a modest contribution to the protective effect of M-CSF against UC. Subsequently, as an in vivo validation model, DSS-induced colitis was employed to demonstrate that M-CSF treatment significantly ameliorated weight loss, disease activity index (DAI) scores, colon shortening, and histological damage. Additionally, M-CSF treatment also significantly reduced M1 macrophage infiltration, elevated levels of aconitate as well as itaconate, and decreased the levels of pro-inflammatory cytokines in colitis. These results demonstrated that aconitate inhibited the expression of pro-inflammatory cytokines through its enzymatic conversion into the immunometabolite itaconate by aconitate decarboxylase 1 (Acod1), and downregulated the levels of M1 macrophages, thereby ameliorating colitis.Conclusion These findings suggest that M-CSF is an important anti-inflammatory cytokine in UC, which may be a promising therapeutic target in the treatment of UC.
研究领域:
免疫学
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胃肠病学
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遗传学
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代谢组学
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炎症研究
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生物医学研究
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产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
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2022
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IF 8.786
Zhang Nan,Gao Xiaochen,Zhang Weijia,Xiong Junyao,Cao Xiaojian,Fu Zhen F.,Cui Min
Japanese encephalitis virus (JEV) is one of the most important members of the flavivirus family. It is a typical zoonotic pathogen that has caused substantial social and economic losses worldwide. The relation between JEV-induced immunosuppression and inflammatory responses has not been thoroughly investigated. In this study, cells infiltrating the brain tissue of JEV-infected mice were mainly identified as monocytic myeloid-derived suppressor cells (M-MDSCs), which subsequently differentiated into CD3+ macrophages. Co-culture with T cells showed that both splenic M-MDSCs and brain infiltrated M-MDSCs isolated from JEV-infected mice inhibited T cell proliferation through ARG1 and iNOS. The splenectomy model revealed that JEV-induced M-MDSCs were mainly derived from bone marrow and migrated to the spleen and central nervous system (CNS). The results of the transcriptome analysis and IRF7-deficient mice indicated that the ZBP1-IRF7 signaling pathway stimulated by JEV RNA played a central role in the induction of M-MDSCs. M-MDSCs migrated into the CNS through the chemokine CCL2/N-CCL2 derived from astrocytes and brain infiltrated M-MDSCs differentiated into CD3+ macrophages through a mechanism mediated by M-CSF, IL-6 and IFN-γ in the brain microenvironment. These findings provide evidence for the mechanism that JEV regulates the differentiation of M-MDSCs and thereby exacerbates pathogenicity, which represents a potential therapeutic target for Japanese encephalitis (JE).
研究领域:
免疫学
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神经病毒学
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病毒学
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致病机制
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产品关联
DOI
PubMed
高影响因子
Nano Research
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2024
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IF 9.5
Zhao Ze Qiang,Chen Bo Zhi,Gan Jia Li,Feng Yun Hao,Liang Ling,Yu Lingyun,Wang Zi Yi,Abbaszadeh Samin,Shahbazi Mohammad-Ali,Yu Ruixing,Guo Xin Dong
Modulating the immune microenvironment to establish sustained positive feedback within immune pathways represents a promising avenue for the treatment of autoimmunity. However, the precise and efficient delivery of therapeutic systems to the subcutaneous basal layer to modulate immune disorders is a major challenge in the treatment of autoimmune psoriasis. In this project, we introduce a dual-functional microneedle (DF-MN) designed to combine MNs with multiple release kinetics and immunotherapy, the programmed treatment is achieved through segmented design of the MN structure, realizing the unification of rapid and long-lasting treatment of autoimmune psoriasis. In vivo imaging results showed that GelMA@M-CSF showed fluorescent signals after 5 days of delivery to subcutaneous tissues, whereas HA@IL-13 showed minimal fluorescent signals after 2 days. The multistage release behavior of MNs and the diffusion mechanism of drugs were explained at the molecular level, in combination with coarse-grained molecular dynamics. Additionally, DF-MN can successfully induce macrophage reprogramming in vitro and ameliorate overall symptoms in a psoriasis mice model, suggesting that it has the potential to be an effective strategy for the treatment of psoriasis and portends to be a transformative platform for the treatment of other autoimmune diseases.
研究领域:
生物医学工程
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免疫学
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药学
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分子生物学
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产品关联
DOI
高影响因子
iScience
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2021
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IF 5.458
Yuying Zhang,Anqi Guo,Cheng Lyu,Ran Bi,Zhaozhao Wu,Wenjing Li,Peng Zhao,Yudi Niu,Jie Na,Jianzhong Jeff Xi,Yanan Du
Summary It is still a challenge for synthesizing ‘cellular niche-mimics’ in vitro with satisfactory reproducibility and fidelity to recreate the natural niche components (e.g., extracellular matrices and soluble factors) for stem cell cultivation. Inspired by the massive amplification of hepatic progenitor cells during liver fibrosis in vivo , here we optimized the in vitro liver fibrotic niches and subsequently harvested their bioactive ingredients as niche extracts (NEs). The fibrosis-relevant NE marginally outperformed Matrigel for phenotype maintenance of human embryonic stem cell (hESC)-derived hepatoblasts (HBs) and recapitulation of the pathological angiogenesis of hESC-derived endothelial cells both in 2D culture and 3D liver organoids. Finally, defined NE components (i.e., collagen III, IV, IL-17, IL-18 and M-CSF) were resolved by the quantitative proteomics which exhibited advantage over Matrigel for multi-passaged HB expansion. The pathology-relevant and tissue-specific NEs provide innovative and generalizable strategies for the discovery of optimal cellular niche and bioactive niche compositions.
研究领域:
干细胞生物学
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组织工程
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细胞微环境
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蛋白质组学
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类器官培养
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）