Yinpeng Jin , Xianming Meng , Zhiping Qian , Jun Zhao , Ying Lv , Yun Ling , Xiaohong Fan
{"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 , Xianming Meng , Zhiping Qian , Jun Zhao , Ying Lv , Yun Ling , 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":"2025-06-14","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":"Gliadin amplifies the macrophage response triggered by stressed beta cells","authors":"Tina Zenia Jørgensen , Knud Josefsen , Signe Stentoft Dissing , Karsten Buschard , Julie Christine Antvorskov , 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":"2025-06-14","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":"Macrophage heterogeneity in autoimmune diseases","authors":"Shuaiyi Li, Xiaohui Zhou, Shidi Yu, Zenghui Liu, Mingshuang Sun, Zihou Si, 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":"2025-06-13","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}
Dan Wang , Jing Zhao , Chunyan Yang , Daogang Qin , Dengna Zhu
{"title":"Aerobic exercise activates let-7e-5p through TP73-AS1 to inhibit the HMGB1/RAGE axis and alleviate asthma airway inflammation and remodeling","authors":"Dan Wang , Jing Zhao , Chunyan Yang , Daogang Qin , Dengna Zhu","doi":"10.1016/j.cellimm.2025.104990","DOIUrl":"10.1016/j.cellimm.2025.104990","url":null,"abstract":"<div><div>The rising incidence of asthma, a chronic respiratory condition, has been associated with the involvement of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in its pathogenesis. Nevertheless, there is a shortage of data pertaining to the impact of lncRNA TP73-AS1 and let-7e-5p on this disease. Therefore, we aimed to explore the possible effects of aerobic exercise (AE) on lncRNA TP73-AS1, let-7e-5p, inflammation, and high mobility group box 1 (HMGB1)/receptor for advanced glycation end products (RAGE) in asthma mouse models. HMGB1/RAGE was significantly upregulated in asthma mouse models using ovalbumin (OVA) stimulation. The overexpression of let-7e-5p, which was found to be significantly downregulated in asthma mouse models, appeared to inhibit EMT and might alleviate airway inflammation in asthmatic mice through the suppression of the HMGB1/RAGE pathway. Aerobic exercise was associated with reduced airway inflammation and remodeling in asthmatic mice, and appeared to suppress TP73-AS1 expression in asthma OVA-mouse models. Furthermore, TP73-AS1 may exacerbate airway inflammation and remodeling in OVA-induced asthmatic mice by downregulating let-7e-5p expression, which could activate the HMGB1/RAGE-NF-κB pathway. These findings suggest potential innovative approaches for asthma management, which warrant further validation.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"414 ","pages":"Article 104990"},"PeriodicalIF":3.7,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144240096","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}
Raghda Mohammed Ghorab , Hala Ahmed Talkhan , Asmaa Mohamed Abd ElGwad , Rania AbdelMoniem Radwan , Hoda Ezz Elarab Abdelwahab , Doaa Mohamed Abd El Aziz
{"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 , Hala Ahmed Talkhan , Asmaa Mohamed Abd ElGwad , Rania AbdelMoniem Radwan , Hoda Ezz Elarab Abdelwahab , 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":"2025-06-07","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}
Irfan Ahmad , Ahmed Hussein , Bhavesh Kanabar , Abhinav Kumar , T. Ramachandran , Aman Shankhyan , A. Karthikeyan , Dhirendra Nath Thatoi , Zafar Aminov , Hamed Soleimani Samarkhazan , Zahra Jafari
{"title":"“Mesenchymal stem cell-derived exosomes (MSC-exosomes) in hematology: From mechanisms to clinical breakthroughs”","authors":"Irfan Ahmad , Ahmed Hussein , Bhavesh Kanabar , Abhinav Kumar , T. Ramachandran , Aman Shankhyan , A. Karthikeyan , Dhirendra Nath Thatoi , Zafar Aminov , Hamed Soleimani Samarkhazan , 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":"2025-06-03","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}
Hye-Youn Son , Vasso Apostolopoulos , June-Key Chung , Chul-Woo Kim , Ji-Ung Park
{"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 , Vasso Apostolopoulos , June-Key Chung , Chul-Woo Kim , 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":"2025-05-30","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}
Luis Eduardo Alves Damasceno , Gabriel Alberto de Carvalho Barbosa , Tim Sparwasser , Thiago Mattar Cunha , Fernando Queiroz Cunha , José Carlos Alves-Filho
{"title":"PGC1α-mediated mitochondrial fitness promotes Treg cell differentiation","authors":"Luis Eduardo Alves Damasceno , Gabriel Alberto de Carvalho Barbosa , Tim Sparwasser , Thiago Mattar Cunha , Fernando Queiroz Cunha , 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<sub>reg</sub>) 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<sub>reg</sub> cell differentiation remains unclear. Herein, we demonstrated that PGC1α is highly expressed in T<sub>reg</sub> cells compared to other CD4 T cell populations. Using a pharmacological approach, we found that its transcriptional activation in iT<sub>reg</sub> 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<sub>reg</sub> 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<sub>reg</sub> cells as a therapeutic strategy.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"414 ","pages":"Article 104985"},"PeriodicalIF":3.7,"publicationDate":"2025-05-30","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":"Fibrinogen regulates microglial function through the JAK2/STAT3 signaling pathway","authors":"Xiaohui Li , Xiujuan Song , Fei Yi , 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":"2025-05-27","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}