Cellular immunology最新文献

{"title":"Quercetin alleviates diabetic nephropathy by inhibiting M1 macrophage polarization via targeting NLRC5/NLRP3 pathway","authors":"Abudoushalamu Abudoureyimu ,&nbsp;Chen Chen ,&nbsp;Yan Hu ,&nbsp;Dilihumaer Nuermaimaiti ,&nbsp;Tao Liu","doi":"10.1016/j.cellimm.2025.104997","DOIUrl":"10.1016/j.cellimm.2025.104997","url":null,"abstract":"<div><h3>Background</h3><div>The activation imbalance of M1/M2 macrophage phenotypes is crucial in diabetic nephropathy (DN). This study aimed to explore the molecular mechanisms underlying quercetin's action against DN.</div></div><div><h3>Methods</h3><div><em>In vitro</em>, RAW 264.7 macrophages were incubated with high glucose (HG) with or without quercetin. Overexpression of NLRC5 was investigated to elucidate the mechanism. M1/M2 macrophage differentiation was assessed by flow cytometry using cell surface markers CD86 and CD206. <em>In vivo</em>, a DN mouse model was created using a high-fat diet and streptozotocin (STZ). Quercetin was administered intragastrically to DN mice at 50 mg/kg and 100 mg/kg. After euthanasia, mouse kidneys were analyzed by hematoxylin and eosin (H&amp;E), Masson's trichrome, and immunohistochemistry (IHC) staining. ELISA assay and western blot analysis were performed to determine related molecular levels.</div></div><div><h3>Results</h3><div><em>In vitro</em>, quercetin significantly reduced HG-induced expressions of CD86, iNOS, NLRC5, NLRP3, and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), while increasing HG-induced CD206, Arg-1, and IL-10 in RAW 264.7 macrophages. However, these effects of quercetin were abolished when NLRC5 was overexpressed. In DN mice, quercetin administration ameliorated renal histopathological injury and fibrosis. Notably, there was a significant reduction in expressions of NLRC5, NLRP3, Col1a1, and α-SMA, along with decreased expressions of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β).</div></div><div><h3>Conclusion</h3><div>This study showed that quercetin improves DN by inhibiting M1-type macrophages through targeting the NLRC5/NLRP3 pathway.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"414 ","pages":"Article 104997"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144470934","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}

{"title":"“Mesenchymal stem cell-derived exosomes (MSC-exosomes) in hematology: From mechanisms to clinical breakthroughs”","authors":"Irfan Ahmad ,&nbsp;Ahmed Hussein ,&nbsp;Bhavesh Kanabar ,&nbsp;Abhinav Kumar ,&nbsp;T. Ramachandran ,&nbsp;Aman Shankhyan ,&nbsp;A. Karthikeyan ,&nbsp;Dhirendra Nath Thatoi ,&nbsp;Zafar Aminov ,&nbsp;Hamed Soleimani Samarkhazan ,&nbsp;Zahra Jafari","doi":"10.1016/j.cellimm.2025.104986","DOIUrl":"10.1016/j.cellimm.2025.104986","url":null,"abstract":"<div><div>Mesenchymal stem cells (MSCs) offer promising therapy because they regulate the immune system and help repair tissues. However, challenges such as low cell survival rates, immune rejection, and ethical concerns related to their clinical use have limited their widespread application. To overcome these limitations, MSC-derived exosomes (MSC-EXOs) have emerged as an innovative and promising cell-free therapeutic strategy. MSC-EXOs are nanosized extracellular vesicles released by MSCs that carry a diverse array of bioactive molecules, including proteins, lipids, and nucleic acids. They share many benefits with MSCs, including immune regulation, anti-inflammatory effects, and tissue repair. MSC-EXOs demonstrate therapeutic potential by modulating the tumor microenvironment, suppressing tumor growth, and enhancing the efficacy of conventional therapies. They can specifically target cells, deliver therapeutic agents, and induce apoptosis in cancer cells. Additionally, MSC-EXOs can modulate the immune response, promote hematopoietic recovery, and alleviate treatment-related side effects. While MSC-EXOs present a promising therapeutic approach, several challenges remain, including the standardization of isolation and characterization methods, understanding their mechanisms of action, and ensuring both safety and efficacy. Despite these challenges, the future of MSC-EXO-based therapies in hematology is promising. Continued research efforts are essential to unravel the intricate biology of exosomes, identify novel biomarkers, and develop innovative therapeutic strategies. By harnessing the power of MSC-EXOs, we can revolutionize the treatment of hematological diseases and improve patient outcomes.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"414 ","pages":"Article 104986"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144240103","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}

{"title":"Zinc finger protein 217 contributes to natural killer cell dysfunction in murine colorectal cancer","authors":"Yibing Yu ,&nbsp;Huanbin Yang ,&nbsp;Hao Wang ,&nbsp;Fei Xiao","doi":"10.1016/j.cellimm.2025.104971","DOIUrl":"10.1016/j.cellimm.2025.104971","url":null,"abstract":"<div><div>Immune cells play active roles in the surveillance and control of colorectal cancer (CRC) progression. Natural killer (NK) cells are powerful anti-tumor effector cells but their regulatory mechanisms in the CRC tissues have not been thoroughly elucidated. In this research using a murine inflammatory colorectal cancer model, we characterized the phenotype and function of NK cells. We found signs of NK cell dysfunction in CRC tissues, including up-regulation of exhaustion markers, down-regulation of activating receptors, deficiencies in degranulation and cytokine expression, and weak cytolytic effect. Interestingly, zinc finger protein 217 (ZNF217), a transcription repressor, was significantly up-regulated in CRC-associated NK cells. <em>In vitro</em> assays revealed that ZNF217 knockdown promoted NK cell cytolytic activity, implying that ZNF217 is an inhibitory factor of NK cell function. Adoptive transfer assays indicated that ZNF217 knockdown also resulted in enhancement of NK cell function <em>in vivo</em> and subsequently suppressed CRC development. Furthermore, hypoxia rather than exhaustion up-regulated ZNF217 expression in NK cells. ZNF217 knockdown promoted NK cell resistance to hypoxia-mediated NK cell dysfunction. Therefore, we discovered a novel regulatory factor of NK cell dysfunction during CRC development.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"413 ","pages":"Article 104971"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071331","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}

{"title":"METTL3 facilitates osteoblast differentiation and bone regeneration via m6A-dependent maturation of pri-miR-324-5p","authors":"Jing Xiao ,&nbsp;Zhiyuan Xu ,&nbsp;Zhiwei Deng ,&nbsp;Juntong Xie ,&nbsp;Yiyan Qiu","doi":"10.1016/j.cellimm.2025.104974","DOIUrl":"10.1016/j.cellimm.2025.104974","url":null,"abstract":"<div><h3>Background</h3><div>Osteoblast differentiation is essential for fracture healing and bone regeneration. miR-324-5p has been implicated in osteoporosis, but its precise role in osteogenic differentiation remains unclear. We investigated the function and regulatory mechanisms of miR-324-5p in bone marrow mesenchymal stem cells (BMSCs).</div></div><div><h3>Methods</h3><div>RT-qPCR was used to assess miR-324-5p expression during osteogenic differentiation of BMSCs. ALP, Alizarin Red S (ARS), Oil Red O, and TRAP staining were performed to evaluate osteoblast, adipocyte, and osteoclast differentiation. Rat femoral fracture and calvarial bone defect models were established to assess in vivo bone regeneration. Methylated RNA immunoprecipitation (MeRIP) and luciferase reporter assays were used to investigate METTL3-mediated m6A modification of pri-miR-324-5p and its regulation of ELAVL1.</div></div><div><h3>Results</h3><div>miR-324-5p expression increased during osteogenic differentiation, and ALP and ARS staining confirmed enhanced osteoblast activity and mineralization following miR-324-5p overexpression. Meanwhile, Oil Red O staining showed reduced adipogenic differentiation, and TRAP staining demonstrated suppressed osteoclast formation. In vivo, miR-324-5p promoted bone healing, bone mass, and bone regeneration. Mechanistically, METTL3-mediated m6A modification facilitated pri-miR-324-5p maturation, positively regulating its expression. Additionally, miR-324-5p directly targeted ELAVL1, and ELAVL1 overexpression reversed the osteogenic effects of miR-324-5p.</div></div><div><h3>Conclusion</h3><div>The METTL3/miR-324-5p/ELAVL1 axis plays a crucial role in osteogenic differentiation and bone regeneration, providing new insights into m6A modification-driven osteogenesis.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"413 ","pages":"Article 104974"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144107557","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}

{"title":"Investigating the effect of neuro-immune communication on immune responses in health and disease: Exploring immunological disorders","authors":"Fatemeh Hesampour ,&nbsp;Charles N. Bernstein ,&nbsp;Jean-Eric Ghia","doi":"10.1016/j.cellimm.2025.104963","DOIUrl":"10.1016/j.cellimm.2025.104963","url":null,"abstract":"<div><div>Recent recognition of the intricate nervous-immune system interplay has prompted research into the specific cellular components involved in these interactions. Emerging evidence suggests that immune and neural cells collaborate within distinct units and act in concert to regulate tissue function and provide protection. These specialized neuro-immune cell units have been identified in diverse body tissues, ranging from lymphoid organs to the bone marrow and mucosal barriers. Their significance has become increasingly apparent as they are recognized as pivotal regulators influencing a broad spectrum of physiological and pathological processes. This recognition extends to critical roles in hematopoiesis, organ function, inflammatory responses, and intricate tissue repair processes. This review explores the bidirectional communication between the nervous and immune systems. The focus is on understanding the profound impact of this communication on immune cells within key anatomical sites, such as the bone marrow, gastrointestinal tract, and lymphoid organs. By examining these interactions, this review aims to shed light on how this intricate network operates under normal and pathological conditions, offering insights into the mechanisms underlying health and disease.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"413 ","pages":"Article 104963"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144069956","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}

{"title":"Progress of exosomes in regulating tumor metastasis by remodeling the pre-metastatic immune microenvironment","authors":"Jiangning Xiang,&nbsp;Lin Yao,&nbsp;Shan Wang,&nbsp;Lei Zhao,&nbsp;Jing Yu","doi":"10.1016/j.cellimm.2025.104960","DOIUrl":"10.1016/j.cellimm.2025.104960","url":null,"abstract":"<div><div>Exosomes play an important role in the metastatic microenvironment, acting as a transmission belt that facilitates intercellular communication. By delivering proteins, nucleic acids, and other substances in the exosomes, they can change the function of the receptor target cells, change the microenvironment of the metastatic site, and promote the colonization of the tumor cells, thus promoting cancer metastasis. The interaction between tumor cells and the surrounding microenvironment is complex, with exosomes serving as key facilitators of crosstalk between the primary tumor microenvironment and the pre-metastasis microenvironment. Despite many current studies to explore exosomes, we still do not have a detailed understanding of the role and mechanism of exosomes in the pre-metastatic immune microenvironment, and there are many challenges in the clinical application of exosomes. In this paper, we summarize the role of exosomes in regulating the pre-metastatic immune microenvironment and its mechanism, focusing on how exosomes regulate the function of immune cells in the pre-metastatic microenvironment to promote tumor metastasis. In addition, the potential application of exosomes in tumor immunotherapy and strategies for targeting exosomes are discussed. This will contribute to the immunotherapy of cancer metastasis and promote the clinical application of exosomes.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"413 ","pages":"Article 104960"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942679","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}

{"title":"Apelin-13 enhances neurofunctional recovery and suppresses neuroinflammation via the SIRT1/NF-κB axis in ischemic stroke","authors":"Zhe Peng ,&nbsp;Dewen Ru ,&nbsp;Guangpeng Leng ,&nbsp;Jinghua Peng ,&nbsp;Meng Zhang ,&nbsp;Bin Cai","doi":"10.1016/j.cellimm.2025.104958","DOIUrl":"10.1016/j.cellimm.2025.104958","url":null,"abstract":"<div><h3>Background</h3><div>Ischemic stroke is a major cause of mortality and disability, with neuroinflammation driving secondary brain injury. Microglial activation contributes to neuronal apoptosis, BBB disruption, and prolonged neurological deficits. Apelin-13, an endogenous peptide, has demonstrated neuroprotective potential, but its precise mechanisms remain unclear. This study investigates how Apelin-13 modulates neuroinflammation and the molecular pathways involved in ischemic stroke.</div></div><div><h3>Methods</h3><div>Mice underwent middle cerebral artery occlusion-reperfusion (MCAO/R) to model ischemic stroke, followed by Apelin-13 administration. Neurological function was assessed using Garcia scoring, adhesive removal, rotarod, and grid-walking tests. Infarct volume was quantified via TTC staining, and MRI evaluated cerebral edema. Immunofluorescence staining and Western blotting were used to assess neuronal apoptosis and BBB integrity. Microglial activation and polarization were analyzed via Iba1 co-immunostaining with CD16 (pro-inflammatory) and Arg1 (anti-inflammatory) markers. In vitro, primary microglia and BV2 cells were exposed to oxygen-glucose deprivation (OGD) to mimic ischemia, and Apelin-13's effects on inflammatory signaling were examined. The role of the SIRT1/NF-κB axis was evaluated using the SIRT1 inhibitor EX-527.</div></div><div><h3>Results</h3><div>Apelin-13 significantly improved post-stroke neurological function, reduced infarct volume, and alleviated cerebral edema. It preserved BBB integrity by reducing vascular leakage and albumin extravasation and suppressed neuronal apoptosis by downregulating cleaved caspase-3. Apelin-13 also mitigated neuroinflammation by decreasing microglial activation and shifting polarization toward an anti-inflammatory phenotype, as evidenced by reduced CD16+ and increased Arg1+ microglia. In vitro, Apelin-13 suppressed OGD-induced pro-inflammatory cytokine release while promoting anti-inflammatory responses. Mechanistically, Apelin-13 upregulated SIRT1, inhibiting NF-κB signaling and reducing inflammatory mediator expression. SIRT1 inhibition with EX-527 reversed these effects, restoring NF-κB activation and pro-inflammatory microglial polarization.</div></div><div><h3>Conclusions</h3><div>Apelin-13 exerts neuroprotective effects in ischemic stroke by preserving BBB integrity, reducing neuronal apoptosis, and suppressing neuroinflammation. These effects are mediated through SIRT1 activation and NF-κB inhibition. Targeting the Apelin-13/SIRT1/NF-κB axis may offer a promising therapeutic strategy for mitigating neuroinflammation and improving stroke recovery.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"413 ","pages":"Article 104958"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144069955","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}

{"title":"Modular activation of macrophage-like cells by beta-2-microglobulin via mitochondria and the cGAS-STING pathway","authors":"Josefine Kofoed Corneliussen ,&nbsp;Helena Borland Madsen ,&nbsp;Nadia Thaulov Zelander ,&nbsp;Mogens Holst Nissen ,&nbsp;Claus Desler","doi":"10.1016/j.cellimm.2025.104962","DOIUrl":"10.1016/j.cellimm.2025.104962","url":null,"abstract":"<div><div>Beta-2-microglobulin (β2m) is a component of the major histocompatibility complex class I. β2m is released into cellular fluids in response to various stimuli, including pro-inflammatory cytokines. Elevated β2m levels have been found associated with autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and Crohn's disease, as well as in various hematological cancers and viral infections. Despite an established correlation between immune activation of especially monocytes and macrophages, and circulating β2m levels, the causative relationship remains unclear. Here, we investigate the effects of exogenous β2m and a complement C1s cleaved form, dK58β2m, on two murine macrophage-like cell lines J774 and RAW. We demonstrate that β2m, and to a greater extent dK58β2m, can affect mitochondrial activity. Furthermore, the presence of IFN-γ amplifies the effect, causing altered bioenergetics, and increased production of mitochondrial reactive oxygen species and nitric oxide. In addition, we found activation of the cGAS-STING pathway by β2m and dK58β2m in the presence of IFN-γ. Only dK58β2m in combination with IFN-γ caused apoptosis and cell death. Our findings highlight the modular nature of a β2m-induced macrophage response, potentiated by dK58β2m and IFN-γ, and provide information on the underlying mechanisms responsible for the immune activation properties of β2m.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"413 ","pages":"Article 104962"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143922628","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}

{"title":"Tribute to Mike Cancro – Former editor-in-chief at Cellular Immunology","authors":"Simon Fillatreau ,&nbsp;Yi Hao","doi":"10.1016/j.cellimm.2025.104973","DOIUrl":"10.1016/j.cellimm.2025.104973","url":null,"abstract":"","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"413 ","pages":"Article 104973"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144221263","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}

{"title":"Retraction notice to \"Protective efficacy of a plasmid DNA vaccine against transgene-specific tumors by Th1 cellular immune responses after intradermal injection\" [Cell. Immunol. 329 (2018) 17–26]","authors":"Hye-Youn Son ,&nbsp;Vasso Apostolopoulos ,&nbsp;June-Key Chung ,&nbsp;Chul-Woo Kim ,&nbsp;Ji-Ung Park","doi":"10.1016/j.cellimm.2025.104975","DOIUrl":"10.1016/j.cellimm.2025.104975","url":null,"abstract":"","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"413 ","pages":"Article 104975"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186607","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}