Molecular immunology最新文献

{"title":"Gastric cancer mesenchymal stem cells upregulate PD-1 expression on the CD8⁺ T cells by regulating the PI3K/AKT pathway.","authors":"Weimeng Ji, Juan Xu, Chao Huang, Ting Liu, Shihan Chen, Yuanyuan Zhao, Chenglin Zhou, Li Sun, Mei Wang, Deqiang Wang, Wei Zhu","doi":"10.1016/j.molimm.2025.01.005","DOIUrl":"https://doi.org/10.1016/j.molimm.2025.01.005","url":null,"abstract":"<p><p>Gastric cancer mesenchymal stem cells (GC-MSCs) are a crucial component of the gastric cancer microenvironment, exerting a pivotal influence on the formation of a suppressive immune microenvironment and the progression of gastric cancer. In this study, we utilized GC-MSCs to co-culture peripheral blood mononuclear cells (PBMCs) obtained from both gastric cancer patients and healthy individuals in a proportionate manner by direct cell-to-cell contact. Our findings reveal that co-culture of GC-MSCs with PBMCs led to a notable reduction in CD8⁺ T cells percentages and an increase in surface PD-1 expression levels on CD8⁺ T cells. However, flow cytometry analysis demonstrated no significant changes following pretreatment with GC-MSC-conditioned medium (GC-MSC-CM). Moreover, western blotting analysis demonstrated a notable reduction in phosphorylated AKT levels in co-cultured PBMCs. Collectively, our results suggest that GC-MSCs impair the anti-tumor immune response of PBMCs by elevating the PD-1 levels of CD8⁺ T cells and impairing the killing of CD8⁺ T cells. These findings provide new evidence that GC-MSCs contribute to immunosuppression within the tumor microenvironment (TME).</p>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"178 ","pages":"97-106"},"PeriodicalIF":3.2,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052452","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":"Silibinin, a PLC-β3 inhibitor, inhibits mast cell activation and alleviates OVA-induced asthma.","authors":"Tzu-Ting Chen, Juan-Cheng Yang, Guan-Yu Chen, Yun-Hao Dai, Xiang Zhang, Hong-Lin Chan, Tim Cc Lin, Yang-Chang Wu","doi":"10.1016/j.molimm.2025.01.009","DOIUrl":"https://doi.org/10.1016/j.molimm.2025.01.009","url":null,"abstract":"<p><p>The immunoglobulin E (IgE) receptor FcεRI (Fc epsilon RI) plays a crucial role in allergic reactions. Recent studies have indicated that the interaction between FcεRIβ and the downstream protein phospholipase C beta 3 (PLCβ3) leads to the production of inflammatory cytokines. The aim of this study was to develop small molecules that inhibit the protein-protein interactions between FcεRIβ and PLCβ3 to treat allergic inflammation. Additionally, PLCβ3 has emerged as a potential target protein for treating allergic inflammation. In this study, we employed a virtual screening technique to search the Taiwan Traditional Chinese Medicine Database, followed by a second screening using absorption, distribution, metabolism, excretion, and toxicity (ADMET). Among the compounds screened, silibinin exhibited the best performance, forming strong hydrogen bond interactions with residues of PLCβ3, with a binding free energy of -119.277 kcal/mol. Therefore, silibinin effectively blocked the interaction between FcεRIβ and PLCβ3. Silibinin reduced the production of allergic inflammatory cytokines, including cytokine-induced neutrophil chemoattractant 2a (CINC-2a), interleukin-2 (IL-2), cytokine-induced neutrophil chemoattractant 1 (CINC-1), interleukin 1α (IL-1α), macrophage inflammatory protein 3 alpha (MIP3α), interferon γ (IFN-γ), activin A, granulocyte macrophage colony stimulating factor (GM-CSF), intercellular adhesion molecule-1 (ICAM-1), interleukin 4 (IL-4), interleukin 13 (IL-13), Fas ligand (FasL) and tumor necrosis factor alpha (TNF-α), without inducing cytotoxicity. Furthermore, in studies of IgE-mediated allergic responses, silibinin also decreased the expression of surface IgE receptors (FcεRIs). Moreover, silibinin effectively alleviated allergen-induced asthma responses and reduced the infiltration of inflammatory immune cells into the lungs of an OVA-induced allergic airway inflammation mouse model. Taken together, these results demonstrate the potential antiallergic mechanism of silibinin both in vitro and in vivo, making it a promising candidate for the development of asthma therapeutics.</p>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"178 ","pages":"76-86"},"PeriodicalIF":3.2,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052492","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":"Immunological characteristics of peripheral T cells as prognostic markers for Camrelizumab and Apatinib combination therapy in advanced squamous non-small-cell lung cancer.","authors":"Liangliang Wu, Xiaoyu Zhi, Shengzhi Xie, Keren Li, Man Chen, Gong Li, Qiyan Wu, Shunchang Jiao, Jinliang Wang, Tianyi Liu","doi":"10.1016/j.molimm.2025.01.011","DOIUrl":"https://doi.org/10.1016/j.molimm.2025.01.011","url":null,"abstract":"<p><strong>Purpose: </strong>To determine the characteristic changes of peripheral blood T cells and identify potential biomarkers that associated with the clinical efficacy of combined immunotherapy and anti-angiogenic therapy in patients with advanced squamous non-small cell lung cancer (NSCLC).</p><p><strong>Methods: </strong>We performed a comprehensive immunological assessment of peripheral blood mononuclear cell samples from advanced squamous NSCLC patients before and after combination of immunotherapy (Camrelizumab) and anti-angiogenic therapy (Apatinib) using spectral flow cytometry. Correlations between these immunological features and clinical efficacy were analyzed.</p><p><strong>Results: </strong>Our findings revealed that, following two treatment cycles, the concentration of type 1 T helper (Th1) cells in the peripheral circulation was significantly higher in the responder group than in the non-responder group, correlating with a statistically significant improvement in survival outcomes. Post-treatment, CD137 expression within Th1 cells in the responders, whereas TIM-3 expression was significantly reduced. In the validation cohort, elevated CD4⁺ CXCR3⁺ CD137⁺ cells in the peripheral blood were associated with a positive clinical reaction to the treatment and extended survival.</p><p><strong>Conclusions: </strong>Our findings suggest that peripheral blood circulating CD4⁺ CXCR3⁺ CD137⁺ cells serve as biomarkers of response to combined immunotherapy and anti-angiogenic therapy in patients with advanced squamous NSCLC, providing potential guidance for improving clinical outcomes.</p>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"178 ","pages":"87-96"},"PeriodicalIF":3.2,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052454","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":"Genetically engineered bacteria expressing IL-34 alleviate DSS-induced experimental colitis by promoting tight junction protein expression in intestinal mucosal epithelial cells.","authors":"Weijie Chen, Tongtong Zhou, Yicun Liu, Leilei Luo, Yujing Ye, Lixian Wei, Jian Chen, Zhaolian Bian","doi":"10.1016/j.molimm.2025.01.008","DOIUrl":"https://doi.org/10.1016/j.molimm.2025.01.008","url":null,"abstract":"<p><strong>Background: </strong>The intestinal mucosa of ulcerative colitis patients expresses high levels of interleukin 34, and mice lacking IL-34 have more severe DSS-induced experimental colitis. There are no studies on the effects of directly upregulating intestinal IL-34 on experimental colitis in mice.</p><p><strong>Methods: </strong>The bacteria EcN/CSF-1 and EcN/IL-34, which express CSF-1 and IL-34, respectively, were genetically engineered from Escherichia coli Nissle 1917 (EcN). Colitis mice received daily gavage of sterile PBS buffer, empty plasmid E. coli (EcN/WT), EcN/CSF-1, or EcN/IL-34. Each group of mice was assessed for body mass, clinical signs, DAI, intestinal mucosal permeability, pathological, and immunohistological changes. In vitro, NCM460 cells were treated with CSF-1 or IL-34 recombinant proteins in the presence of signaling pathway inhibitors to evaluate tight junction protein expression. Additionally, intestinal mucosal epithelial cells isolated from active UC patients were analyzed for IL-34 and tight junction protein levels.</p><p><strong>Results: </strong>DSS-induced colitis mice are protected by EcN/IL-34 gavage. Pathological results showed that EcN/IL-34 group colonic histological injury was significantly improved and tight junction protein ZO-1 and Occludin expression increased. In NCM460 cells, IL-34 also increased tight junction protein expression. More importantly, expression of IL-34 was positively correlated with the level of tight junction protein expression in epithelial cells of UC patients.</p><p><strong>Conclusion: </strong>EcN/IL-34 can directly act on damaged intestinal mucosa, up-regulate IL-34 expression, and promote tight junction protein expression in intestinal mucosal epithelial cells to alleviate experimental colitis in mice. IL-34 may be a potential therapeutic target for ulcerative colitis, and genetically engineered bacteria carrying the cytokine may offer new ideas for treating UC.</p>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"178 ","pages":"64-75"},"PeriodicalIF":3.2,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047358","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":"Screening for immunodominant epitopes of SARS-CoV-2 based on CD8⁺ T cell responses from individuals with HLA-A homozygous alleles.","authors":"Rui He, Lingxin Meng, Yuting Sun, Jingsong Wang, Shufeng Wang, Yueping Liu, Lei Fei, Zhongfang Wang, Qinggao Zhang, Yuzhang Wu, Yongwen Chen, Bo Diao","doi":"10.1016/j.molimm.2025.01.010","DOIUrl":"https://doi.org/10.1016/j.molimm.2025.01.010","url":null,"abstract":"<p><strong>Purpose: </strong>SARS-CoV-2-specific CD8⁺ cytotoxic T lymphocytes (CTLs) are crucial in viral clearance, disease progression, and reinfection control. However, numerous SARS-CoV-2 immunodominant CTL epitopes theoretically are still unidentified due to the genetic polymorphism of human leukocyte antigen class I (HLA-I) molecules.</p><p><strong>Methods: </strong>The CTL epitopes of SARS-CoV-2 were predicted by the epitope affinity and immunogenicity prediction platforms: the NetMHCpan and the PromPPD. Individuals with HLA-A homozygous alleles were screened from 252 COVID-19 vaccinees, including the Ad5-nCoV vaccine (CanSino, n = 183) and the CoronaVac inactivated vaccine (Sinovac, n = 69) using MiSeqDx™ generation sequencing, and their PBMCs were further stimulated by the predicted peptides to screen the immunodominant epitopes according to the secretion of IFN-γ from CD8⁺ T cells. Peptide-MHC tetramers were constructed and used to detect the frequency of antigen specific CTLs in vivo.</p><p><strong>Results: </strong>Individuals with HLA-A homozygous alleles including HLA-A*01 (n = 1), -A*02 (n = 9), - A*03 and -A*11 (n = 12), and -A*24 (n = 7) supertypes were selected. Twelve immunodominant CTL epitopes for these HLA-A allotypes were finally screened based on the frequency of IFN-γ⁺CD8⁺ T cells in homozygous individuals. The SARS-CoV-2 specific CTLs from Omicron variant infected patients were successfully evaluated by these novel peptide-HLA tetramers.</p><p><strong>Conclusion: </strong>A set of immunodominant CTL epitopes of SARS-CoV-2 was identified, and the antigen-specific CD8⁺ T cells in viral infected patients or COVID-19 vaccinees could be rapidly detected by a mixture of the peptide-MHC tetramers.</p>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"178 ","pages":"52-63"},"PeriodicalIF":3.2,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047359","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":"Muscle fiber types switched during the development of experimental autoimmune myasthenia gravis via the PI3K/Akt signaling pathway.","authors":"Xinrong Li, Xiuhua Yao, Wei Zhao, Bo Wei, Ran Zhang, Geng Yan, Mingyu Ma, Zhenhai Wang, Xijun Liu, Yumei Liu, Guangyou Wang, Hulun Li, Qingfei Kong, Jinghua Wang, Lili Mu","doi":"10.1016/j.molimm.2025.01.006","DOIUrl":"https://doi.org/10.1016/j.molimm.2025.01.006","url":null,"abstract":"<p><p>As one of the largest organs of our human body, skeletal muscle has good research prospects in myasthenia gravis (MG), the symptoms of which include systemic skeletal muscle weakness. Skeletal muscle is composed of two types of muscle fibers. Different fiber subtypes can be converted into each other; however, the underlying mechanism is not yet clear. In this paper, we firstly established an experimental autoimmune myasthenia gravis (EAMG) rat model and found that the skeletal muscle fibers of the EAMG group were atrophied, with a change in the proportion of fiber subtypes, which switched from type IIa to type I in the EAMG group at the peak stage, as verified by histological and molecular analyses. Second-generation sequencing results predicted that the PI3K-Akt signaling pathway might be involved in the switch, and the mRNA expression levels of the PI3K-Akt pathway-related genesNr4a1, IL2rb, Col1A1 and Ddit4 were significantly different. In conclusion, this study indicates that the switch of muscle fiber subtypes in MG via the PI3K-Akt signaling pathway may be a potential target for the treatment of MG-related skeletal muscle atrophy in the future.</p>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"178 ","pages":"41-51"},"PeriodicalIF":3.2,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008720","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":"Identification and characterization of the Cul t 1 as major allergen from biting midge Culicoides tainanus.","authors":"Shuncai Bao, Guangpeng Li, Xue Lu, Tengfei Lu, Xiaohui Hou","doi":"10.1016/j.molimm.2025.01.004","DOIUrl":"https://doi.org/10.1016/j.molimm.2025.01.004","url":null,"abstract":"<p><strong>Background: </strong>Midges are widely distributed globally. They can transmit numerous serious diseases as well as trigger an allergic reaction in the host. Their saliva contains a variety of proteins that act as sensitizers to stimulate the host's immune response, leading to IgE-mediated allergic symptoms.</p><p><strong>Material and method: </strong>In the present study, we constructed a mouse sensitization model with the thorax extract of the Culicoides tainanus, and evaluated the sensitization model by behavior and specific antibody expression. SDS-PAGE/western blot was used to detect the binding proteins by IgE antibody in the thorax extract of the C. tainanus. The objective band was cut for mass spectrometry to preliminarily clarify the potential allergen. The pET21a-Cul t 1 recombinant expression vector was constructed and the target protein was purified by Ni affinity chromatography. The sensitizing effect of the sensitizer was verified in vitro and in vivo.</p><p><strong>Results: </strong>Immunoblot analysis revealed that a 66 kDa protein (Cul t 1) from the chest extracts of C. tainanus could bind to serum IgE of sensitized mice. Cul t 1 was further identified by fragmentation, mass spectrometry and bioinformatics as maltase, an enzyme involved in sugar digestion. In vivo validation of the Cul t 1-mouse sensitization model showed that the scratching behavior of the Cul t 1 sensitized group was significantly higher than that of the control group according to behavioral evaluation. The results of HE staining of the skin of the injected area showed that Cul t 1 sensitized group was found to have a large number of inflammatory cell infiltration and increased fibrosis in the dermis. The ELISA detection of IgE showed that the Cul t 1 sensitized group was significantly elevated from the beginning of the 28th day onwards, and the expression level of IgE had a tendency to slow down with the prolongation of the sensitization time. The ELISA assay showed that the expression level of IgG1 increased significantly in the Cul t 1 group on day 42, while the results of the specific antibody IgG2a showed that there was no significant difference in both the Cul t 1 sensitized group and the control group. The results suggest that the immune response induced by Cul t 1 sensitized mice may be shifted toward a Th2 type immune response.</p><p><strong>Conclusions: </strong>In this study, we identified the sensitizer of the C. tainanus, named Cul t 1. We successfully constructed the recombinant expression vector pET21a-Cul t 1, purified the Cul t 1 sensitizer by affinity chromatography, and verified the sensitizing effect of Cul t 1 in mice. The results laid a practicable foundation for the subsequent immune therapy of midge bites and bite control.</p>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"178 ","pages":"32-40"},"PeriodicalIF":3.2,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008718","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":"TRIM44 alleviates renal ischemia-reperfusion injury by inhibiting pyroptosis through the NLRP3 pathway.","authors":"Jinzhuo Ning, Jinrun Wang, Xuan Sun, Haoyong Li, Fan Cheng","doi":"10.1016/j.molimm.2025.01.003","DOIUrl":"https://doi.org/10.1016/j.molimm.2025.01.003","url":null,"abstract":"<p><strong>Background: </strong>Renal ischemia-reperfusion injury (IRI) is a prevailing manifestation of acute kidney injury (AKI) with limited treatment options. TRIM44 has emerged as a possible target for treatment due to its regulatory function in inflammatory pathways.</p><p><strong>Methods: </strong>In vivo and in vitro models were employed to ascertain the TRIM44 impact on renal IRI. In vivo, we induced IRI in mice and assessed histological changes, oxidative stress markers, and pyroptosis-related proteins. In vitro, we subjected renal cells to hypoxia/reoxygenation (H/R) and manipulated TRIM44 expression to evaluate its effects on cell viability and pyroptosis.</p><p><strong>Results: </strong>IRI significantly increased inflammation, oxidative stress, and pyroptosis in both animal and cell models, evidenced by elevated cleaved caspase-1, GSDMD-N, and IL-1β/-18 levels. IRI conditions experienced a mitigated TRIM44 expression. Overexpression of TRIM44 in renal cells reduced pyroptosis, as shown by decreased levels of pyroptosis-related proteins and inflammatory cytokines and improved cell viability. Mechanistically, TRIM44 inhibited the NLRP3 inflammasome, as evidenced with reduced NLRP3 and cleaved caspase-1 levels upon TRIM44 overexpression and NLRP3 inhibition. In vivo, intravenous administration of TRIM44-expressing adenovirus post-IRI ameliorated renal damage, as reported with mitigated serum creatinine and blood urea nitrogen levels.</p><p><strong>Conclusion: </strong>TRIM44 protects against renal IRI by inhibiting pyroptosis via the NLRP3 pathway, suggesting its potential to be targeted therapeutically for treating AKI.</p>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"178 ","pages":"20-31"},"PeriodicalIF":3.2,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008722","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":"Esophageal squamous cell carcinoma derived sEV-PDL1 exhausts CD8⁺T cells to promote immunosuppression.","authors":"Zijie Li, Xiaokuan Zhang, Yuying Qi, Zhiyu Wang","doi":"10.1016/j.molimm.2025.01.001","DOIUrl":"https://doi.org/10.1016/j.molimm.2025.01.001","url":null,"abstract":"<p><p>Esophageal squamous cell carcinoma (ESCC) is a common malignancy. Programmed death ligand 1 of small extracellular vesicles (sEV-PDL1) induce immune evasion and enhance tumor progression. However, the role of ESCC derived sEV-PDL1 in modulating CD8⁺T cell remains unclear. sEVs were isolated through differential centrifugation. CD8⁺T cells were isolated, stimulated and cultured with sEVs to evaluate the proportions, phenotypes, and functions by flow cytometry. Lentivirus infection and Crisper-Cas9 were used to constructed stable transgenic cell lines: Eca109-PDL1^kd and mEC25-PDL1^ko. The proportions of CD8⁺T cells in ESCC patients was lower than healthy donors (HD). Furthermore, a negative correlation between sEV-PDL1 and CD8⁺T cell was observed. sEV-PDL1 induced CD8⁺T cell exhaustion by reducing the expression levels of Ki67, Granzyme B (GrzmB), and interferon-γ (IFN-γ) both in vitro and in vivo. However, anti-PDL1 reversed the result. Our findings reveal that targeting sEV-PDL1 to rejuvenate CD8⁺T cell functions is one of the mechnisms a promising therapeutic strategy for ESCC.</p>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"178 ","pages":"12-19"},"PeriodicalIF":3.2,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971520","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":"LincR-PPP2R5C regulates the PP2A signaling pathway in the macrophage-myofibroblast transition in a mouse model of epidural fibrosis.","authors":"Jinpeng Sun, Mohan Shi, Rui Mei, Youpeng Zhao, Yue Huang, Zeyuan Song, Feng Hua, Mingshun Zhang, Jun Liu","doi":"10.1016/j.molimm.2024.12.006","DOIUrl":"10.1016/j.molimm.2024.12.006","url":null,"abstract":"<p><p>Low back pain after spine surgery is a major complication due to excessive epidural fibrosis, which compresses the lumbar nerve. Macrophage-myofibroblast transition (MMT) promoted epidural fibrosis in a mouse laminectomy model. Previously, we demonstrated that LincR-PPP2R5C regulated CD4 + T-cell differentiation. Here, we aimed to explore the roles and mechanisms of LincR-PPP2R5C in macrophages in epidural fibrosis. In M2 macrophages, the level of LincR-PPP2R5C was significantly decreased. Upon overexpression, LincR-PPP2R5C induced M1-macrophage polarization and reduced MMT. In contrast, LincR-PPP2R5C deficiency promoted M2-macrophage polarization and increased MMT. Mechanistically, LincR-PPP2R5C modulated the expression of α-SMA in macrophages via the PP2A signaling pathway. In vivo, LincR-PPP2R5C deficiency aggravated epidural fibrosis by enhancing MMT in a mouse model of laminectomy, and this effect was abolished in mice with macrophage depletion. Our study shed light on the effects of LincR-PPP2R5C on macrophage differentiation and MMT in epidural fibrosis.</p>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"177 ","pages":"85-95"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896202","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}