Cellular immunology最新文献

{"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":"2025-08-01","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":"Efficacy and safety of interferon alpha-2b aerosol therapy for patients infected with the SARS-CoV-2 omicron variant: A randomized controlled single-blind study","authors":"Yinpeng Jin ,&nbsp;Xianming Meng ,&nbsp;Zhiping Qian ,&nbsp;Jun Zhao ,&nbsp;Ying Lv ,&nbsp;Yun Ling ,&nbsp;Xiaohong Fan","doi":"10.1016/j.cellimm.2025.104992","DOIUrl":"10.1016/j.cellimm.2025.104992","url":null,"abstract":"<div><div>The efficacy of Type I interferon (IFN) in treating COVID-19 has remained controversial. In this study, we conducted a randomized, single-blind clinical trial to evaluate the efficacy of recombinant human interferon alpha 2b (IFN-alpha2b) in treating COVID-19 patients during the Omicron outbreak in Shanghai in 2022. The study cohort included 505 patients, classified as asymptomatic, mild, or moderate based on clinical symptoms. The cohort was divided into an experimental group, which received a 7-day course of nebulized inhalation of IFN-alpha2b, and a control group, which received an identical treatment course using physiological saline in place of IFN-alpha2b. Effectiveness and safety were assessed by measuring the length of hospital stay, improvement in clinical symptoms, and occurrence of adverse events. While there were no significant differences in overall hospital stay or symptom improvement between the two groups, IFN-alpha2b treatment was associated with a significantly shorter hospitalization time in the asymptomatic subgroup. Multivariate Cox regression analysis identified IFN nebulization therapy as a positive predictor of discharge within 12 days, alongside the white blood cell count at admission, and the IL-4 level at admission as a potential negative predictor. Regarding safety, there was no significant difference in the incidence of adverse reactions between the two groups during treatment. Collectively, our study suggests that Type I IFN, when administered via nebulized inhalation, may offer benefits specifically for the asymptomatic subgroup among COVID-19 patients, indicating selective efficacy.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"414 ","pages":"Article 104992"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144364751","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":"2025-08-01","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}

{"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":"2025-08-01","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":"Gliadin amplifies the macrophage response triggered by stressed beta cells","authors":"Tina Zenia Jørgensen ,&nbsp;Knud Josefsen ,&nbsp;Signe Stentoft Dissing ,&nbsp;Karsten Buschard ,&nbsp;Julie Christine Antvorskov ,&nbsp;Jesper Larsen","doi":"10.1016/j.cellimm.2025.104989","DOIUrl":"10.1016/j.cellimm.2025.104989","url":null,"abstract":"<div><div>In humans, a gluten-free diet can slow disease progression and improve clinical outcome in newly diagnosed type 1 diabetes patients. In NOD mice, the incidence of autoimmune diabetes is influenced by both beta cell activity and gluten. Here, we demonstrate that metabolically stressed pancreatic cell lines (MIN6, beta TC3, and alpha TC3) effectively activated macrophage RAW 264.7 cells. Gliadin further enhanced this response in MIN6 cells but had no such effect on beta TC3 or alpha TC3 cells. Additionally, gliadin directly stimulated MIN6 cells, affecting pathways related to cellular activation, stress responses, and immune regulation. These findings provide insights into the in vivo benefits of a gluten-free diet in type 1 diabetes development by highlighting the roles of cellular stress and gliadin in disease progression.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"414 ","pages":"Article 104989"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144280705","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":"Fibrinogen regulates microglial function through the JAK2/STAT3 signaling pathway","authors":"Xiaohui Li ,&nbsp;Xiujuan Song ,&nbsp;Fei Yi ,&nbsp;Huiqing Hou","doi":"10.1016/j.cellimm.2025.104976","DOIUrl":"10.1016/j.cellimm.2025.104976","url":null,"abstract":"<div><h3>Background</h3><div>Neuroinflammation, a defining feature of numerous neurological disorders, arises predominantly from activating immune cells such as microglia, which play a critical role in maintaining homeostasis within the central nervous system. Microglial activation and polarization exhibit a dual nature, mediating both neuroprotective and neurotoxic effects. Fibrinogen, as a potent pro-inflammatory mediator, interacts with microglia and is implicated in the progression of various neurological conditions. This study investigates the effects of fibrinogen and the exogenous STAT3 inhibitor cryptotanshinone on primary microglial function.</div></div><div><h3>Methods</h3><div>Primary microglial cells were isolated from neonatal C57BL/6 mice and subsequently treated with fibrinogen and the STAT3 inhibitor cryptotanshinone. Inflammatory marker expression was quantified by quantitative polymerase chain reaction, while protein levels of JAK2 and STAT3 were determined using immunofluorescence and Western blot analysis.</div></div><div><h3>Results</h3><div>Fibrinogen exposure upregulated STAT3 and JAK2 phosphorylation in primary microglial cells. Cryptotanshinone treatment effectively attenuated STAT3 phosphorylation while concurrently downregulating JAK2 activation. Furthermore, fibrinogen significantly enhanced the release of pro-inflammatory cytokines, such as IL-6 and IL-1β, while the transcription levels of TGF-β remained unchanged.</div></div><div><h3>Conclusions</h3><div>This study demonstrates that fibrinogen stimulates the production of pro-inflammatory cytokines in primary microglial cells by activating the JAK2/STAT3 signaling pathway. These findings provide mechanistic insights into fibrinogen-induced neuroinflammation and suggest potential therapeutic targets for neurological diseases.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"414 ","pages":"Article 104976"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204243","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":"MEX3A activates the JAK-STAT pathway to suppress NK cell cytotoxicity and accelerate lung adenocarcinoma progression","authors":"Jigui Peng ,&nbsp;Haiqiang Yan ,&nbsp;Wang Zhou ,&nbsp;Hui Chen ,&nbsp;Tao Xu ,&nbsp;Changjin He","doi":"10.1016/j.cellimm.2025.104994","DOIUrl":"10.1016/j.cellimm.2025.104994","url":null,"abstract":"<div><h3>Background</h3><div>Therapeutic potential of natural killer (NK) cells is recognized in treating lung adenocarcinoma (LUAD), but impairment of NK cell functions in various cancers weakens anti-tumor capabilities. Uncovering molecular mechanisms is imperative for fortifying NK cells against degradation and for enhancing their cancer-inhibiting functions.</div></div><div><h3>Methods</h3><div>TCGA-LUAD database complemented by qRT-PCR presented MEX3A expression in LUAD. TIMER was employed to explore relationship between MEX3A levels and NK cell infiltration. In the co-culture system of LUAD and activated NK92 cells, CytoTox 96® assay was applied to gauge NK cell cytotoxicity. ELISA was used to quantify IFN-γ, Perforin, and Granzyme B in the supernatant. Flow cytometry assessed LUAD cell apoptosis. Single-gene enrichment analysis of MEX3A was performed with KEGG database. Western blot examined protein expression in JAK-STAT signaling. In vivo studies validated the role of MEX3A expression on tumorigenesis.</div></div><div><h3>Results</h3><div>MEX3A was upregulated in LUAD tissue and cells, negatively linked to NK cell infiltration levels. Gene set enrichment analysis pointed to influences of MEX3A expression on dynamics of JAK-STAT signaling. MEX3A overexpression in LUAD cells impaired NK cell cytotoxicity and cell apoptosis, and these effects were reversible by a JAK pathway inhibitor. Mouse studies illustrated that LUAD progression was curbed by MEX3A suppression, alongside an enhanced presence of NK cells within tumor microenvironment.</div></div><div><h3>Conclusion</h3><div>To synthesize our results, this study identified that MEX3A in LUAD promoted malignancy of the disease by enhancing JAK-STAT signaling, which in turn inhibited cytotoxic capabilities of NK cells, thus providing novel insights for LUAD immunotherapy.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"414 ","pages":"Article 104994"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144307342","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":"PGC1α-mediated mitochondrial fitness promotes Treg cell differentiation","authors":"Luis Eduardo Alves Damasceno ,&nbsp;Gabriel Alberto de Carvalho Barbosa ,&nbsp;Tim Sparwasser ,&nbsp;Thiago Mattar Cunha ,&nbsp;Fernando Queiroz Cunha ,&nbsp;José Carlos Alves-Filho","doi":"10.1016/j.cellimm.2025.104985","DOIUrl":"10.1016/j.cellimm.2025.104985","url":null,"abstract":"<div><div>Regulatory T (T_reg) cells play a critical role in the maintenance of immune tolerance to self-antigens and suppression of excessive immune responses. They employ a distinct metabolic profile from other CD4 T cell subsets to support their differentiation and suppressive function, which is characterized by enhanced mitochondrial metabolism. Although PGC1α is considered a master regulator of mitochondrial biogenesis and function, its role in T_reg cell differentiation remains unclear. Herein, we demonstrated that PGC1α is highly expressed in T_reg cells compared to other CD4 T cell populations. Using a pharmacological approach, we found that its transcriptional activation in iT_reg cells enhanced mitochondrial fitness, characterized by increased expression of mitochondrial genes, mitochondrial mass, and metabolic activity. Moreover, PGC1α activation enhanced both mouse and human iT_reg cell differentiation, while its inhibition reduced this process. Therefore, our findings shed light on the potential role of PGC1α as a pharmacological target when manipulating T_reg cells as a therapeutic strategy.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"414 ","pages":"Article 104985"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144212781","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":"A novel approach to hematopoietic stem cell transplantation: The effect of CMV infection and HLA genotypes on chimerism status in Egyptian patients","authors":"Raghda Mohammed Ghorab ,&nbsp;Hala Ahmed Talkhan ,&nbsp;Asmaa Mohamed Abd ElGwad ,&nbsp;Rania AbdelMoniem Radwan ,&nbsp;Hoda Ezz Elarab Abdelwahab ,&nbsp;Doaa Mohamed Abd El Aziz","doi":"10.1016/j.cellimm.2025.104991","DOIUrl":"10.1016/j.cellimm.2025.104991","url":null,"abstract":"<div><div>Several studies have investigated the association between HLA alleles and cytomegalovirus (CMV) infection following hematopoietic stem cell transplantation (HSCT). It was found that many HLA alleles were associated with increased rate of CMV infection, while others had a protective effect against infection. However, to our knowledge no studies have investigated the effect of this relation on chimerism status post transplantation. Previous results concluded that CMV reactivation or infection increases conversion from mixed chimerism toward complete chimerism (CC) as a consequence of concomitant activation of immune system. Our aim is to study the association of CMV and certain HLA alleles and their effect on chimerism status post transplantation and identify other factors affecting chimerism status. 165 patients who underwent allogeneic HSCT for different hematological indications were studied. Both recipients (R) and donors (D) underwent serological testing for CMV-specific IgG and IgM, HLA typing, and chimerism analysis. CMV infection or reactivation was assessed in recipients through weekly monitoring of CMV DNA. Patients were followed up for 100 days where chimerism analysis was performed at 28, 60, 90, and 100 days post-transplantation. Eighty-five patients were positive for CMV by PCR post transplantation while eighty patients were CMV negative. Acute graft versus host disease (aGvHD) was significantly increased in CMV positive patients. Multivariate analysis (MVA) has indicated that HLA-A*2, HLA-B*14, HLA-B*41, HLA-DRB1*04 and HLA-DRB1*13, as well as a diagnosis of myelodysplastic syndrome and bone marrow aplasia, significantly increased the risk for CMV positivity post transplantation. HLA-DRB1*11 positivity was associated with a higher rate of aGvHD. CMV infection/reactivation as indicated by positive CMV PCR post-transplant was associated with a faster rate of conversion toward CC, and this effect was independent of the implemented conditioning regimen or the presence of aGvHD. Additionally, D+/R- transplant setting was significantly associated with early CC. On MVA, CMV reactivation was associated with acceleration of conversion toward CC, while HLA-A*33, HLA-DRB1*13, HLA-DRB1*15 and D−/R+ transplant setting were factors associated with delayed CC. In conclusion, CMV infection/reactivation and D+/R- transplant setting were associated with earlier conversion toward CC. Chronic GvHD and early chimerism were associated with better overall survival (OS), while advanced recipient age and HLA-DRB1*01 were associated with lower OS.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"414 ","pages":"Article 104991"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144280704","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":"Macrophage heterogeneity in autoimmune diseases","authors":"Shuaiyi Li,&nbsp;Xiaohui Zhou,&nbsp;Shidi Yu,&nbsp;Zenghui Liu,&nbsp;Mingshuang Sun,&nbsp;Zihou Si,&nbsp;Wei Zhu","doi":"10.1016/j.cellimm.2025.104993","DOIUrl":"10.1016/j.cellimm.2025.104993","url":null,"abstract":"<div><div>The pathogenesis of autoimmune diseases (AIDs) is complex and their etiology remains unclear, with multiple cell types involved in the disease progression. Macrophages, as a crucial immune cell population in AIDs, play a pivotal role in maintaining immune homeostasis. In traditional research, macrophages are frequently oversimplified into the M1 and M2 polarized subtypes. The advent of single-cell RNA sequencing (scRNA-seq) technology has significantly advanced high-throughput research in the life sciences, enabling in-depth investigations at the cellular and molecular levels. This technology has revealed the significant heterogeneity of macrophages, further enhancing our understanding of their development, phenotypic diversity, and functional plasticity. Additionally, it provides a novel perspective for exploring the molecular mechanisms underlying various diseases. In this review, we comprehensively explore the heterogeneity of macrophages across different AIDs, and summarize potential therapeutic targets for macrophage-directed interventions, aiming to provide valuable theoretical insights and novel research directions to advance precision therapy and related studies in AIDs.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"414 ","pages":"Article 104993"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144280814","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}