Molecular immunology最新文献

{"title":"SMAD7-mediated ferroptosis in macrophages drives osteoporosis progression: A multi-omics study","authors":"Qianning Li ,&nbsp;Yucheng Tu ,&nbsp;Hengyi Diao ,&nbsp;Linli Zheng ,&nbsp;Weishen Chen","doi":"10.1016/j.molimm.2025.08.021","DOIUrl":"10.1016/j.molimm.2025.08.021","url":null,"abstract":"<div><div>Osteoporosis (OP) is characterized by imbalanced bone homeostasis, which is difficult to precisely regulate with current therapeutic strategies. Macrophages play a significant role in bone remodeling due to their complex interactions with osteoclasts and osteoblasts, suggesting that targeting macrophage-related pathways could offer novel therapeutic opportunities. To explore this, we combined bulk RNA-seq and scRNA-seq data to identify macrophage-related genes. Using bioinformatic tools, including CIBERSORT, WGCNA, and machine learning algorithms, we identified 1705 macrophage marker genes and 839 macrophage module genes. Enrichment analysis revealed that the intersection genes were significantly enriched in the ferroptosis signaling pathway, highlighting its critical role in macrophages. Further validation through protein-protein interaction networks and cellular communication analysis confirmed the importance of ferroptosis in macrophage. Using artificial neural network, we identified 4 macrophage hub genes, with SMAD7 showing the greatest weight. Experimental validation using RAW264.7 cells, immunohistochemistry, and micro-CT analysis further demonstrated the association of ferroptosis-related indicators (Fe^2 + and lipid peroxidation) with bone damage in osteoporosis patients. And we found SMAD7 showing the strongest correlation with trabecular microstructural deterioration. Notably, our findings also confirmed that the SMAD7 inhibitor mongersen effectively attenuated macrophage ferroptosis, suggesting its potential to improve bone microstructural integrity. Our study demonstrates that SMAD7-mediated macrophage ferroptosis is a critical mechanism in osteoporosis pathogenesis, highlighting SMAD7 as a promising therapeutic target.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 11-27"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144921145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protocatechuic aldehyde promotes diabetic wound healing by enhancing angiogenesis via H3K18 lactylation-mediated Acvr1c expression","authors":"Weijing Fan ,&nbsp;Yang You ,&nbsp;Yin Qu,&nbsp;Guobin Liu","doi":"10.1016/j.molimm.2025.09.002","DOIUrl":"10.1016/j.molimm.2025.09.002","url":null,"abstract":"<div><div>Delayed wound recovery is a major health issue affecting people with diabetes. Histone lactylation is involved in tissue repair. However, it is not clear whether protocatechuic aldehyde (PCA) promotes diabetic wound healing through histone lactylation. In this study, a diabetic wound mouse model was constructed to delve into the role of PCA in vivo. Chromatin immunoprecipitation sequencing (ChIP-seq) was used to determine genes affected by H3K18 lactylation (H3K18la) under PCA treatment. The effects and mechanisms of PCA on histone lactylation and angiogenesis were investigated through cellular experiments. We found that PCA accelerated wound healing and angiogenesis in diabetic mice, and significantly reduced the inflammatory response in wound tissues. Lactate and H3K18la levels were augmented in the model group in comparison with the control group, however, PCA treatment remarkably reversed their levels. ChIP-seq analysis revealed a significant enrichment of H3K18la at the Acvr1c locus, and this histone modification was downregulated by PCA treatment. PCA remarkably enhanced Acvr1c expression through H3K18la in HUVECs. Moreover, PCA treatment markedly elevated cell viability, migration and tube formation in comparison with the control group. However, this effect was counteracted by Acvr1c knockdown. In conclusion, PCA promoted HUVEC angiogenesis by increasing H3K18la-mediated Acvr1c expression, thereby promoting diabetic wound healing. This could offer a new treatment approach to enhance the effectiveness of healing diabetic wounds.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 152-165"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diosgenin ameliorates CLP-induced sepsis in mice via suppressing inflammatory responses and preserving intestinal mucosal barrier integrity","authors":"Yuanyuan Li ,&nbsp;Jiajia Zeng ,&nbsp;Xuan Zhong ,&nbsp;Qiting Huang ,&nbsp;Xianfei Wang ,&nbsp;Shuya Sun ,&nbsp;Huamin Wang ,&nbsp;Xiaoqi Huang ,&nbsp;Jiajun Ling ,&nbsp;Rongfeng Lin","doi":"10.1016/j.molimm.2025.10.005","DOIUrl":"10.1016/j.molimm.2025.10.005","url":null,"abstract":"<div><h3>Background</h3><div>Diosgenin, a well-known steroid sapogenin, has demonstrated anti-inflammatory effects; however, its therapeutic potential for sepsis remains unclear. Intestinal barrier dysfunction is a critical contributor to lethal sepsis, a systemic inflammatory response syndrome. This study investigated the protective effects of diosgenin on cecal ligation and puncture (CLP)-induced sepsis in mice, focusing on its impact on intestinal mucosal dysfunction and inflammation. Additionally, the effects of diosgenin on the expression of the endogenous antimicrobial peptide mCRAMP and the TLR4/MyD88 signaling pathway were investigated.</div></div><div><h3>Methods</h3><div>Sepsis was induced in male C57BL/6 mice via CLP. Survival rates were recorded, and serum and ileum tissue levels of TNF-α and IL-6 were quantified to assess the protective efficacy of diosgenin treatment. Intestinal barrier integrity was evaluated by hematoxylin and eosin (H&amp;E) staining, while mucosal permeability was determined using serum D-lactic acid. Tight junction (TJ) proteins were detected via Western blotting. Immunohistochemistry was used to measure mCRAMP protein expression in the ileum, and quantitative real-time PCR (qRT-PCR) was employed to analyze the gene expression of mCRAMP, TLR4, and MyD88. Molecular docking was performed with Autodock4 software to predict the binding capacity between diosgenin and LL-37, TLR4 and MyD88.</div></div><div><h3>Results</h3><div>Diosgenin treatment significantly improve the survival of mice, decreased TNF-α and IL-6 production, and attenuated intestinal histopathological damage. Additionally, diosgenin decreased serum D-lactic acid levels, upregulated Claudin-1 and Occludin expression, and increased both mRNA and protein levels of mCRAMP while downregulating the gene expression of TLR4 and MyD88. Molecular docking analysis demonstrated favorable binding affinities of diosgenin to LL-37 (−6.3 kcal/mol), TLR4 (−8.3 kcal/mol), and MyD88 (−10.5 kcal/mol). All calculated binding energies were &lt; −5.0 kcal/mol, suggesting potential effective binding of diosgenin to these targets.</div></div><div><h3>Conclusion</h3><div>Diosgenin improved survival, suppressed inflammatory responses, and preserving intestinal mucosal barrier integrity in CLP-induced septic mice. These protective effects might involve alterations in mCRAMP expression and TLR4/MyD88 signaling.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 210-220"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145302166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AMPK upregulates SOCS1 to promote TFEB nuclear transfer, enhances autophagy, inhibits macrophage M1 polarization and relieves acute lung injury","authors":"Wensha Nie ,&nbsp;Chuxiong Gong ,&nbsp;Yongze Liu,&nbsp;Jiawu Yang,&nbsp;Qinglang Dai,&nbsp;Yuan Liao,&nbsp;Feng Li","doi":"10.1016/j.molimm.2025.10.002","DOIUrl":"10.1016/j.molimm.2025.10.002","url":null,"abstract":"<div><h3>Background</h3><div>Acute lung injury (ALI) is a life-threatening inflammatory disease. Macrophage polarization plays a key role in the occurrence of pulmonary inflammation. Therefore, regulating the phenotype of macrophages is a potentially effective method for the treatment of ALI. This study aims to explore the potential molecular mechanism of SOCS1 in M1 polarization of macrophages and ALI.</div></div><div><h3>Methods</h3><div>The ALI animal model was established by intratracheal infusion of LPS (5 mg/kg), and the cell model was established by stimulating RAW264.7 macrophages with LPS (1 μg/mL). The levels of autophagy and macrophage markers were detected by immunofluorescence, MDC staining, western blot. ELISA was used to measure the levels of inflammatory cytokines. The level of MPO in the lungs was determined, and inflammatory cells and proteins in BALF were detected.</div></div><div><h3>Results</h3><div>The expressions of SOCS1, TFEB and p-AMPK decreased in the ALI model. Overexpression of SOCS1 inhibited the M1 polarization of macrophages induced by LPS, reduced the expressions of pro-inflammatory factors IL-1β, IL-6 and TNF-α, increased the expression of anti-inflammatory factor IL-10, and decreased the expressions of iNOS, CD80 and CD86, and increase the expressions of Arg1, CD206 and CD163. Further studies have revealed that SOCS1 activates autophagy by up-regulating the expression of TFEB, thereby inhibiting the polarization of M1 in macrophages. Furthermore, SOCS1 can promote the nuclear translocation of TFEB, while the phosphorylation of AMPK can up-regulate SOCS1 to promote the expression of TFEB.</div></div><div><h3>Conclusion</h3><div>AMPK promotes nuclear transfer of TFEB by up-regulating SOCS1, thereby enhancing autophagy and inhibiting M1 polarization in macrophages, thus alleviating ALI.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 240-253"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypocontractile airway smooth muscle phenotype exhibits enhanced β2 laminin chain expression in lung allergy model","authors":"Ivonne Pacheco-Alba ,&nbsp;Blanca Bazán-Perkins","doi":"10.1016/j.molimm.2025.09.003","DOIUrl":"10.1016/j.molimm.2025.09.003","url":null,"abstract":"<div><div>Sensitization with ovalbumin (OVA) in guinea pigs to induce anti-OVA IgE generates various allergic response phenotypes. One phenotype, characterized by the absence of bronchial obstruction and airway hyperresponsiveness in response to chronic antigen challenge, is termed non-responding (NR) and exhibits high IFN-γ levels. The Th1 cytokine profile is linked with high laminin β2 expression. This study evaluated laminin β2 expression in the chronic NR phenotype. Guinea pigs were sensitized and challenged with OVA three times (acute) or twelve times (chronic). Guinea pigs that responded to all challenges formed the asthma model phenotype. Controls were sensitized and challenged with saline. Immunohistochemistry was used to observe laminin β2 and its receptor, the α6 integrin subunit, in bronchial and arterial intrapulmonary smooth muscles. Only chronic NR guinea pigs showed increased laminin β2 expression in these muscles, while it remained similar in other groups. The α6 integrin subunit significantly increased in the acute and chronic asthma models, chronic controls, and NR guinea pigs in bronchial smooth muscle. In arterial intrapulmonary smooth muscle, the α6 integrin subunit increased in acute NR and chronic asthma model guinea pigs. The expression of laminin β2 in bronchial and arterial intrapulmonary smooth muscles correlates with α6 integrin subunit levels, and higher levels of laminin β2 were significantly related to reduced antigen-induced bronchial obstruction and reactivity to histamine. The expression of these proteins does not affect the proliferation of pulmonary blood vessels. Laminin β2 chain overexpression is likely involved in the chronic containment of the obstructive allergic response.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 134-141"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145118645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CCL5: An emerging key target and progress in the targeted therapy of hepatocellular carcinoma","authors":"Xiaoli Liu ,&nbsp;Jie Liang ,&nbsp;Lizhen Zhao ,&nbsp;Wei Li ,&nbsp;Luoyang Wang ,&nbsp;Xiao Wang ,&nbsp;Yi Liu ,&nbsp;Mengting Zhou ,&nbsp;Xinqiang Li ,&nbsp;Zhuoyu Jia ,&nbsp;Meiying Song ,&nbsp;Li Zhang ,&nbsp;Yanyan Yang ,&nbsp;Jinzhen Cai ,&nbsp;Bei Zhang","doi":"10.1016/j.molimm.2025.08.023","DOIUrl":"10.1016/j.molimm.2025.08.023","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is a highly prevalent and lethal malignancy, presenting significant challenges in clinical diagnosis and treatment. The chemokine C-C motif ligand 5 (CCL5) plays a pivotal role in HCC pathogenesis. While traditionally viewed primarily as a mediator of immune cell chemotaxis and migration, recent evidence demonstrates that CCL5 directly influences tumor cells, regulating malignant behaviors such as proliferation and invasion. Furthermore, CCL5 recruits diverse immune cells, including immunosuppressive populations, to the tumor microenvironment (TME), remodeling the TME and exerting context-dependent effects that can either promote immune evasion or enhance anti-tumor immunity. This article reviews advances in understanding the mechanisms of CCL5 in HCC and discusses the translational potential of targeting CCL5 for HCC therapy.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 1-10"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144912995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S1PR2-miR-212 feedback loop regulates allergic reactions","authors":"Jaewhoon Jeoung,&nbsp;Hyein Jo,&nbsp;Wonho Kim,&nbsp;Dooil Jeoung","doi":"10.1016/j.molimm.2025.10.001","DOIUrl":"10.1016/j.molimm.2025.10.001","url":null,"abstract":"<div><div>We previously reported the anti-allergic effect of rocaglamide-A (roc-A). Molecular docking analysis showed the binding of roc-A to sphingosine-1-phospahe receptor 2 (S1PR2). This led us to hypothesize that S1PR2 might play a role in allergic reactions. Antigen stimulation increased the expression of S1PR2 in rat basophilic leukemia (RBL2H3 cells). Sphingosine-1-phosphate (S1P) increased the expression of S1PR2 in an antigen-independent manner. S1PR2 was necessary for both allergic reactions <em>in vitro</em> and anaphylaxis. Sphingosine prevented the antigen (DNP-HSA) from increasing the expression of S1PR2 and hallmarks of allergic reactions in RBL2H3 cells. Sphingosine also prevented antigen from increasing the level of reactive oxygen species (ROS). Animal model of passive systemic anaphylaxis (PSA) showed the increased expression of CXCL1. CXCL1 was shown to mediate allergic reactions <em>in vitro</em>. TargetScan predicted the binding of miR-212 to the 3 ´ UTR of S1PR2. The downregulation of S1PR2 prevented antigen from increasing the expression of CXCL1 at the transcriptional level. cmiR-212 was found to decrease the expression of S1PR2 in antigen stimulated RBL2H3 cells. miR-212 mimic decreased the luciferase activity associated with 3 ´ UTR of S1PR2. The miR-212 mimic exerted a negative effect on the passive cutaneous anaphylaxis (PCA). The downregulation of S1PR2 increased the expression of miR-212 in antigen stimulated RBL2H3 cells. This suggests that miR-212 and S1PR2 form negative feedback loops to regulate allergic reactions. Our results show that S1PR2-miR-212 negative feedback loop regulates allergic reactions in vitro and in vivo.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 166-177"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MAP30 inhibits proliferation and metastasis of bladder cancer by increasing EGR1 expression and promoting the transcriptional activation of DUSP1","authors":"Kaiyue Wang ,&nbsp;Qiao Gu ,&nbsp;Chunyan Xue ,&nbsp;Junyu Shi ,&nbsp;Kun Wang ,&nbsp;Xiaozhou He","doi":"10.1016/j.molimm.2025.08.024","DOIUrl":"10.1016/j.molimm.2025.08.024","url":null,"abstract":"<div><div>The confirmed tumor-inhibitory effects of the 30 kDa Momordica anti-human immunodeficiency virus protein (MAP30) have yet to be complemented by an exploration into its mechanism of action on tumor development and metastasis. For this purpose, we delved into the intrinsic mechanism of MAP30 in bladder cancer (BC). Here, we demonstrated that MAP30 markedly suppressed the proliferation, migration, invasion, and angiogenic capabilities of human BC cells <em>in vitro</em>, and the tumor metastatic potential <em>in vivo</em>. Furthermore, our findings showed that MAP30 suppressed the functional activities of BC cells by upregulating the expression levels of early growth response 1 (EGR1). Additionally, our investigation confirmed that EGR1 and dual specificity phosphatase 1 (DUSP1) were down-expressed in BC and had been identified as closely linked to the advancement of BC. DUSP1 was transcriptionally induced by EGR1, and the expression of EGR1 was found to be positively linked with DUSP1 in human BC tissues. The knockdown of EGR1 was found to boost cell invasion, migration, proliferation, and angiogenesis via the MAPK signaling pathway, however, the overexpression of DUSP1 inhibited EGR1 knockdown-induced promotion of these functional activities in BC cells. Furthermore, MAP30 inhibited the invasion, migration, proliferation, and angiogenesis of BC cells by regulating the EGR1-DUSP1 axis. Our study yielded an exhaustive insight into the suppressive actions of MAP30 on BC progression.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 48-60"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monochromatic green light-mediated melatonin promotes cecal barrier function in broilers","authors":"Tao Quan,&nbsp;Ran Li,&nbsp;Yaoxing Chen,&nbsp;Ting Gao","doi":"10.1016/j.molimm.2025.09.004","DOIUrl":"10.1016/j.molimm.2025.09.004","url":null,"abstract":"<div><div>Light plays a crucial role as an environmental factor, greatly affecting chick behavior, production performance and health. Melatonin, an essential marker of photoelectric signaling, plays a role in regulating various physiological functions in broilers, such as gut health. However, whether monochromatic light can mediate melatonin secretion to regulate intestinal function and its regulatory mechanism are not known. In the present study, we showed that monochromatic green light significantly enhanced the mucosal barrier function of the broiler cecum, including the up-regulation of goblet cells and their secreted MUC2 content, tight junction protein expression and enterocyte proliferative viability. However, when the pineal gland was removed, accompanied by a decrease in melatonin content, the green light advantage disappeared and the intestinal mucosal barrier function was severely impaired. Mechanistically, we found that monochromatic green light promotes melatonin secretion, which enters the intestine to bind Mel1a receptors located on macrophage membranes in cecum, inhibits its downstream TLR4/ERK/JNK/NF-κB signaling pathway, promotes M2-type macrophage polarization, reduces intestinal inflammation levels while up-regulating intestinal antioxidant levels, and ultimately strengthens the cecum mucosal barrier function. Our findings provide new theoretical support for the future use of melatonin during intestinal development, as well as theoretical guidance for the proper application of artificial lighting in the modern chicken industry to improve chicken's intestinal health.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 109-120"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145099353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of the heterogeneity in oxidative stress and transcriptional programs within the in vivo microenvironment of ulcerative colitis","authors":"Yongwei Zhuang ,&nbsp;Ran Ye ,&nbsp;Jingyu Chen ,&nbsp;Gefei Chen ,&nbsp;Luyi Chen ,&nbsp;Yabi Zhu ,&nbsp;Shufang Ye ,&nbsp;Yangyang Liu","doi":"10.1016/j.molimm.2025.08.017","DOIUrl":"10.1016/j.molimm.2025.08.017","url":null,"abstract":"<div><h3>Objective</h3><div>Oxidative stress exerts an essential role in the pathogenesis of ulcerative colitis (UC). This study aims to unveil the heterogeneity in oxidative stress among immune cell subpopulations in UC.</div></div><div><h3>Methods</h3><div>Human colon epithelial cells were exposed to 100 ng/mL LPS to stimulate UC, which were administrated with antioxidants 500 mM butylated hydroxyanisole or 20 μM N-acetylcysteine. A single-cell atlas was constructed across UC, and heterogeneous cell subpopulations were evaluated at single-cell and bulk levels.</div></div><div><h3>Results</h3><div>Activation of oxidative stress and inflammatory response, enhanced migration capacity, and impaired tight junction were observed in LPS-induced UC cell models, which were ameliorated by antioxidants. Five cell types: plasma cells, T cells, myeloid cells, and B cells were clustered across UC and control gut biopsies, which were tightly interacted. Myeloid cells were sub-clustered into conventional dendritic cells, M1 macrophages, IL23R⁺ myeloid cells, mast cells, and follicular dendritic cells; T cells were sub-clustered into Th17, CD4⁺ naïve T cells, CD8⁺ cytotoxic T cells, CD4⁺ exhausted T cells, CD8⁺ memory T cells, Tregs, and Th1. The heterogeneous myeloid and T cells was confirmed at the single-cell and bulk levels. The activity of oxidative stress was heterogeneous among diverse myeloid cell or T cell subpopulations, with the strongest activity in M1 macrophages and CD4⁺ exhausted T cells, respectively. It was also found the specific transcriptional programs of M1 macrophages and CD8⁺ cytotoxic T cells.</div></div><div><h3>Conclusion</h3><div>Overall, our findings unveil the heterogeneity in oxidative stress and transcriptional programs among diverse myeloid and T cell subpopulations in UC.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 80-95"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}