Cellular immunology最新文献

{"title":"ANAPC5 mitigates acute lung injury through regulating macrophage M1/M2 polarization via the EGFR/CD24 axis","authors":"Yiqi Wang ,&nbsp;Xiuhua Zhang ,&nbsp;Jiannan Zhang ,&nbsp;Mingbo Zhao,&nbsp;Yang Chong,&nbsp;Quankuan Gu,&nbsp;Xianglin Meng,&nbsp;Mingyan Zhao","doi":"10.1016/j.cellimm.2025.105013","DOIUrl":"10.1016/j.cellimm.2025.105013","url":null,"abstract":"<div><div>Acute lung injury (ALI) is a respiratory disease induced by uncontrolled inflammatory responses in the lungs. The pathological features of ALI include alveolar structural damage and pulmonary edema, which ultimately leads to pulmonary dysfunction. ANAPC5 (Anaphase-promoting complex subunit 5) is an E3 ubiquitin ligase known for its anti-inflammatory properties. This study aims to investigate the effects of ANAPC5 on ALI and its underlying molecular mechanism. In the lung tissue of an ALI mouse model induced by lipopolysaccharide (LPS) administration, we observed downregulation of ANAPC5. Through both <em>in vivo</em> and <em>in vitro</em> experiments, we assessed the effect of ANAPC5 on lung injury by conducting pathological analysis and molecular biological detection. ANAPC5 overexpression alleviated inflammatory cell infiltration, reduced alveolar wall thickening, suppressed pulmonary inflammation, and decreased the levels of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and lung tissue of the ALI model. Moreover, ANAPC5 inhibited M1 polarization and promoted M2 polarization of macrophages both <em>in vitro</em> and <em>in vivo</em>. We also found that ANAPC5 significantly suppressed the activation and expression of the epidermal growth factor receptor (EGFR) through inducing its ubiquitination in macrophages. In LPS-induced M1 macrophages, the presence of EGFR significantly decreased CD24 expression, followed by reversing the inhibitory effects of ANAPC5 on inflammatory responses and macrophage polarization. Collectively, our findings suggest that ANAPC5 serves as a therapeutic molecular target that mitigates ALI through regulating macrophage M1/M2 polarization <em>via</em> the EGFR/CD24 axis.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"415 ","pages":"Article 105013"},"PeriodicalIF":2.9,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144865996","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":"Chloroquine treatment ameliorates experimental autoimmune encephalomyelitis by inhibiting T cell differentiation and pDC accumulation","authors":"Yonghai Li ,&nbsp;Yue Shao ,&nbsp;Xianfen Ma ,&nbsp;Yaning Li ,&nbsp;Yijia Yang ,&nbsp;Fengyuan Wang ,&nbsp;Yushan Yan ,&nbsp;Xiaoxi Hu ,&nbsp;Yujie Dai ,&nbsp;Meng Li ,&nbsp;Max Löhning ,&nbsp;Ping Shen ,&nbsp;Juntang Lin","doi":"10.1016/j.cellimm.2025.105010","DOIUrl":"10.1016/j.cellimm.2025.105010","url":null,"abstract":"<div><h3>Objectives</h3><div>Chloroquine (CQ) has been used to treat rheumatoid arthritis and systemic lupus erythematosus, but its use in multiple sclerosis (MS) is limited by side effects and insufficient efficacy. To enhance treatment outcomes, understanding CQ's therapeutic mechanisms in MS is crucial. Thus, we administered CQ to mice with experimental autoimmune encephalomyelitis (EAE) and investigated its disease-ameliorating effects and underlying cellular mechanisms.</div></div><div><h3>Methods</h3><div>CQ was applied intraperitoneally six days after EAE induction, immune responses, with a focus on inflammatory and regulatory T cells, as well as dendritic cells in blood, lymph nodes, spleen, and bone marrow were analyzed by flow cytometry.</div></div><div><h3>Results</h3><div>CQ treatment significantly reduced cumulative disease score and maximal disease score in CQ-treated group. Immunohistochemical analysis of the spinal cords confirmed the reduced demyelination after CQ treatment, which is accompanied by significantly decreased infiltration of T cells, B cells, and macrophages, and less activated microglia cells. Flow cytometry analysis of peripheral lymphoid organs revealed a significant decrease of inflammatory Th17 cells, which is associated with reduced pDC and their IFN-α expression, as well as Treg cells in CQ-treated mice. Indeed, depletion of pDC alone or simultaneously with CQ treatment significantly reduced EAE severity.</div></div><div><h3>Conclusion</h3><div>Our results demonstrated that CQ treatment inhibits the development of EAE disease on one hand by enhancing the expansion of Treg in dLN and spleen, and on the other hand by inhibiting the accumulation of pDC and their IFN-α expression in the spleen and bone marrow. This joint effort restricts the level of inflammation in peripheral and later in CNS. Furthermore, developing a pDC-targeted CQ treatment will not only increase the treatment efficiency, but also largely decrease side effects.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"415 ","pages":"Article 105010"},"PeriodicalIF":3.7,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144679089","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":"Enhancing the antitumor activity of CD19/BCMA CAR-T cells in vitro with a PD1IL7R chimeric switch receptor","authors":"Kai Yan,&nbsp;Zhongdang Xiao","doi":"10.1016/j.cellimm.2025.105001","DOIUrl":"10.1016/j.cellimm.2025.105001","url":null,"abstract":"<div><div>Chimeric antigen receptor (CAR)-T cell therapy has revolutionized the treatment of hematologic malignancies, but its long-term efficacy is hindered by antigen escape, T-cell exhaustion, and the immunosuppressive tumor microenvironment (TME). Programmed death ligand 1 (PD-L1) expression in the TME inhibits CAR-T cell function, limiting persistence and cytotoxic capacity. To address this, we engineered CD19/BCMA-targeted CAR-T cells co-expressing a PD1IL7R chimeric switch receptor (CSR). This novel receptor converts PD-L1-mediated inhibitory signals into IL7R-driven pro-survival and proliferative pathways, enhancing CAR-T cell expansion, persistence, and cytotoxicity in a PD-L1–dependent but antigen-specific manner. In vitro, CD19/BCMA-PD1IL7R CAR-T cells exhibit improved central memory T-cell formation, increased cytokine secretion, and superior antitumor activity compared to conventional CAR-T cells. Notably, these functional enhancements were evident even at low levels of PD-L1 expression on target cells, and no off-target effects were observed. Our findings suggest that incorporating the PD1-IL7R switch receptor into CAR-T cells effectively overcomes PD-L1–mediated immunosuppression, enhancing both their persistence and antitumor efficacy. This approach offers a versatile strategy for improving CAR-T therapy in the treatment of both hematologic and solid tumors.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"415 ","pages":"Article 105001"},"PeriodicalIF":3.7,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144614817","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":"Identification of Epstein-Barr virus nuclear antigen 1 (EBNA1)-specific T-cell receptors: implications for immunotherapy targeting EBV-associated malignancies","authors":"Ying Liu ,&nbsp;Yaqi Pan ,&nbsp;Huirong Ding ,&nbsp;Wei He ,&nbsp;Huanyu Chen ,&nbsp;Zhe Hu ,&nbsp;Zheming Lu ,&nbsp;Yang Ke","doi":"10.1016/j.cellimm.2025.105002","DOIUrl":"10.1016/j.cellimm.2025.105002","url":null,"abstract":"<div><h3>Background</h3><div>Epstein-Barr virus nuclear antigen (EBNA1) is uniquely expressed across all three EBV latency types, making it an ideal target for TCR-engineered T-cell therapy against EBV-associated malignancies. However, preparation of EBNA1-specific TCR-T cells, particularly for EBV latency I type, remains exploratory.</div></div><div><h3>Methods</h3><div>EBNA1-specific T cells were stimulated using autologous dendritic cells (DCs) pulsed with peptides synthesized from the complete sequence (except the glycine-alanine repeat region) of the EBNA1 of EBV strain B95–8. For pre-stimulated and post-stimulated T cells, candidate EBNA1-specific TCRs with significantly increased frequencies were identified using high-throughput single-cell TCR V(D) J sequencing. The functionality of EBNA1-specific TCR-engineered T cells was assessed <em>in vitro</em> against lymphoblastoid cell lines (LCLs) and EBNA1 peptide-pulsed DCs.</div></div><div><h3>Results</h3><div>EBNA1-specific T cells were successfully expanded. Candidate EBNA1-specific TCRs were isolated, corresponding TCR gene sequences were constructed and introduced into peripheral blood T cells. Engineered T cells expressing EBNA1-specific TCR demonstrated specific recognition of EBNA1 presented by autologous LCLs and DCs <em>in vitro</em>.</div></div><div><h3>Conclusions</h3><div>This study establishes the feasibility of expanding functional EBNA1-specific TCR-T cells, providing a foundation for adoptive cell therapy targeting all EBV-associated malignancies, including latency I.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"415 ","pages":"Article 105002"},"PeriodicalIF":2.9,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144757208","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":"Sfrp2-deficient colonic fibroblasts drive mucosal inflammation and epithelial injury in ulcerative colitis","authors":"Mengyuan Zhu ,&nbsp;Zhanqiu Diao ,&nbsp;Lei Hu ,&nbsp;Zhipeng Fan","doi":"10.1016/j.cellimm.2025.105003","DOIUrl":"10.1016/j.cellimm.2025.105003","url":null,"abstract":"<div><div>Ulcerative colitis (UC) is a chronic inflammatory disorder targeting the colon, which remains clinically challenging due to limited targeted therapies. Although intestinal fibroblasts have emerged as critical regulators of mucosal immunity and tissue repair, their molecular mechanisms in UC pathogenesis are poorly defined. Here, we investigate the functional role of secreted frizzled-related protein 2 (SFRP2, a Wnt signaling modulator) knockdown fibroblasts in immune homeostasis and the severity of UC using <em>Sfrp2</em>^{<em>flox/flox</em>}; <em>Col1a2</em>-Cre mice (fibroblast-specific knockout). In the dextran sulfate sodium (DSS)-induced colitis model, we found SFRP2 in fibroblasts have negative correlation with the severity of UC. That <em>Sfrp2</em>^{<em>Col1a2</em>} CKO mice exhibited exacerbated colitis symptoms and accelerated inflammatory progression, and showed increased ratio of Th17 cells and decreased ratio of Treg cells. These findings revealed that <em>Sfrp2</em> in fibroblasts plays a crucial role in protecting against inflammatory responses and T-cell immune dysregulation. Therefore, <em>Sfrp2</em> may serve as a potential therapeutic target for UC treatment.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"415 ","pages":"Article 105003"},"PeriodicalIF":3.7,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144653934","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":"Acetyl-CoA subcellular compartmentalization regulates T cell adaptation","authors":"Annefien Tiggeler ,&nbsp;Paul J. Coffer","doi":"10.1016/j.cellimm.2025.105000","DOIUrl":"10.1016/j.cellimm.2025.105000","url":null,"abstract":"<div><div>Upon activation, naïve T cells undergo rapid proliferation and differentiation, giving rise to clonally expanded populations specifically tailored for an effective immune response. To meet the heightened bioenergetic and biosynthetic demands associated with activation, T cells adapt and reprogram both their metabolism and transcriptome. Beyond this, T cells are also able to dynamically adapt to fluctuations in the microenvironmental nutrient levels. While the adaptability of T cells is a well-established hallmark of their functionality, the molecular mechanisms by which metabolic responses underpin this flexibility remain incompletely defined. Acetyl-CoA, with its role as a central metabolite in mitochondrial ATP production, and a substrate for nuclear histone acetylation reactions, emerges as a key player in a metabolic-epigenetic axis. Recent evidence indicates that enzymes responsible for generating acetyl-CoA can translocate to the nucleus, supporting sub-cellular local acetyl-CoA production. Here, we explore the impact of acetyl-CoA metabolism on T cell functionality within different subcellular compartments and highlight the potential for intervention in acetyl-CoA metabolic pathways in T cell-driven autoimmune diseases and cancers.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"414 ","pages":"Article 105000"},"PeriodicalIF":3.7,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144563117","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":"Functional avidity enhancement of a T-cell receptor targeting the KRASG12D cancer neoantigen","authors":"Feiyang Luo ,&nbsp;Qiwen Yao ,&nbsp;Yanan Hao ,&nbsp;Meiying Shen ,&nbsp;Tong Chen ,&nbsp;Ruixin Wu ,&nbsp;Tingting Li ,&nbsp;Xiaojian Han ,&nbsp;Aishun Jin","doi":"10.1016/j.cellimm.2025.104999","DOIUrl":"10.1016/j.cellimm.2025.104999","url":null,"abstract":"<div><div>Engineered T cell receptors (TCRs) targeting neoantigens represent a transformative approach in cancer immunotherapy, yet their clinical potential is limited by low natural TCR avidity and the risk of off-target toxicity from over-engineered TCRs with excessive high-affinity. Here, we developed a TCR engineering platform to enhance the functional avidity of a TCR targeting the KRAS G12D mutation (KRAS^G12D) while avoiding reactivity to the wild-type (WT) peptide. We separately constructed CDR3α- and CDR3β-focused TCR libraries derived from an HLA-A*11:01-restricted KRAS^G12D-specific TCR and screened them using alternating positive and negative selection: KRAS^G12D-pulsed antigen-presenting cells (APCs) drove functional avidity, while KRAS^WT-pulsed APCs eliminated cross-reactive clones. From these libraries, we identified CDR3α variants with modest avidity gains and reduced off-target reactivity, and CDR3β variants with significant avidity enhancement and potent tumor cytotoxicity, albeit with variable cross-reactivity profiles. This strategy enables precision engineering of neoantigen-specific TCRs, balancing therapeutic efficacy and safety for adoptive transfer TCR-T therapy.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"414 ","pages":"Article 104999"},"PeriodicalIF":3.7,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144502062","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":"M6A methyltransferase ZC3H13-mediated downregulation of GPX4 mRNA stability inhibits the progression of kidney renal clear cell carcinoma (KIRC)","authors":"Dongli Ruan ,&nbsp;Rui Huang ,&nbsp;Huilong Wang ,&nbsp;Kepu Liu ,&nbsp;Yi Huang ,&nbsp;Zhibin Li","doi":"10.1016/j.cellimm.2025.104998","DOIUrl":"10.1016/j.cellimm.2025.104998","url":null,"abstract":"<div><h3>Background</h3><div>Kidney renal clear cell carcinoma (KIRC) is one of the fatal genitourinary diseases and accounts for most malignant kidney tumors. Previous studies have indicated that RNA modification N6-methyladenosine zinc-finger CCCH-type containing 13 (ZC3H13) plays a vital regulatory role in KIRC. However, the biological role and mechanism of ZC3H13 in KIRC are poorly defined.</div></div><div><h3>Methods</h3><div>TIMER, ENCORI, and UALCAN databases were used to analyze the expression feature and prognostic significance of ZC3H13. ZC3H13 and Glutathione Peroxidase 4 (GPX4) mRNA level and protein level were determined using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. Cell proliferation and apoptosis were measured using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU), and flow cytometry. A xenograft model analyzed the effects of ZC3H13 on tumor growth <em>in vivo</em>. Superoxide dismutase (SOD) activity, Glutathione (GSH) level, and Reactive oxygen species (ROS) were determined using special assay kits. Adenosine triphosphate (ATP) level was detected using kit. Mitochondrial membrane potential changes were analyzed using flow cytometry.</div></div><div><h3>Results</h3><div>ZC3H13 was decreased, and GPX4 was increased in KIRC tissues and cells. Moreover, overexpressing ZC3H13 hindered KIRC cell proliferation, promoted apoptosis, oxidative stress, and disrupted mitochondrial function <em>in vitro</em>, as well as blocked tumor growth <em>in vivo</em>. At the molecular level, ZC3H13 could decrease the stability and expression of GPX4 mRNA <em>via</em> m6A methylation.</div></div><div><h3>Conclusion</h3><div>ZC3H13 destabilizes GPX4 mRNA in an m6A-dependent manner, thereby repressing KIRC cell proliferation, expediting apoptosis, oxidative stress, and impairing mitochondrial function, which provided a promising therapeutic target for KIRC.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"414 ","pages":"Article 104998"},"PeriodicalIF":3.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144490247","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":"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":"2025-06-17","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":"Curcumin mitigates systemic lupus erythematosus by suppressing double-negative T cells through cell apoptosis","authors":"Min Xu ,&nbsp;Xiaoliu Li ,&nbsp;Cheng Bao ,&nbsp;Yue Zhang ,&nbsp;Jinghan Yang ,&nbsp;Yang Hang ,&nbsp;Lingyun Sun ,&nbsp;Hongwei Chen","doi":"10.1016/j.cellimm.2025.104996","DOIUrl":"10.1016/j.cellimm.2025.104996","url":null,"abstract":"<div><h3>Objective</h3><div>Curcumin extracted from the rhizome of <em>Curcuma longa</em> has anti-inflammatory, antioxidant and antitumour properties. In previous studies, curcumin has been reported to have therapeutic effects on systemic lupus erythematosus (SLE), in which the upregulation of double-negative T (DNT) cells was detected. Therefore, the purpose of this study is to explore the role of curcumin in the remission of SLE by regulating DNT cell homeostasis.</div></div><div><h3>Methods</h3><div>Two established murine models of lupus, MRL/<em>lpr</em> mice and R848-induced mice, were administered with 50 mg/kg curcumin to evaluate its therapeutic effects. Flow cytometry was used to detect the proportions of DNT cells, Treg cells and Th cells in mouse tissues. H&amp;E staining and immunofluorescence were used to assess inflammatory cell infiltration and immune complex deposition in the kidney. Enzyme-linked immunosorbent assay <strong>(</strong>ELISA) and real-time quantitative PCR (RT-qPCR) were used to detect the expression of inflammatory factors. RNA sequencing was used to identify differentially expressed genes and explore regulatory mechanisms, and western blot was used to detect protein expression.</div></div><div><h3>Results</h3><div>Our results suggest that the accumulation of DNT cells is closely associated with lupus pathogenesis and development in both mouse models, whereas curcumin treatment can improve lupus serological and immunological profiles, and regulate T-cell homeostasis, especially DNT cells. Further studies demonstrated that curcumin promoted DNT cell apoptosis to eventually decrease the accumulation of DNT cells.</div></div><div><h3>Conclusion</h3><div>Curcumin can improve lupus serological and immunological profiles as well as renal pathology by suppressing DNT cells, and may be a potential candidate for the treatment of SLE.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"414 ","pages":"Article 104996"},"PeriodicalIF":3.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144297665","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}