We studied plasma levels of complement system factors C1q, C2, C3, C3b, C4, C4b, C5, C5a, C9 of 84 patients with ischemic stroke within 24 h from onset of symptoms and on seventh day after admission, using Luminex immunoassay. C1q, C2, C3, C3b, C4, C4b, C5, C5a levels were significantly lower at Day 7, compared to Day 1. Patients with poor outcome (NIHSS ≥16 or death) had significantly higher C9 levels at both time points, and higher C2, C5 and C5a levels on Day 7 than the rest of the group. C2, C5, C5a and C9 correlated with final NIHSS score at both time points. Conclusions: Plasma levels of complement change dynamically within first days of the acute phase of ischemic stroke. Higher baseline C9 is associated with worse outcome in acute phase of ischemic stroke.
{"title":"Complement proteins changes in ischemic stroke patients and their relation to outcome","authors":"Radosław Opiła , Karolina Łuczkowska , Edyta Paczkowska , Przemysław Nowacki , Jarosław Peregud-Pogorzelski , Bogusław Machaliński","doi":"10.1016/j.imbio.2025.153135","DOIUrl":"10.1016/j.imbio.2025.153135","url":null,"abstract":"<div><div>We studied plasma levels of complement system factors C1q, C2, C3, C3b, C4, C4b, C5, C5a, C9 of 84 patients with ischemic stroke within 24 h from onset of symptoms and on seventh day after admission, using Luminex immunoassay. C1q, C2, C3, C3b, C4, C4b, C5, C5a levels were significantly lower at Day 7, compared to Day 1. Patients with poor outcome (NIHSS ≥16 or death) had significantly higher C9 levels at both time points, and higher C2, C5 and C5a levels on Day 7 than the rest of the group. C2, C5, C5a and C9 correlated with final NIHSS score at both time points. Conclusions: Plasma levels of complement change dynamically within first days of the acute phase of ischemic stroke. Higher baseline C9 is associated with worse outcome in acute phase of ischemic stroke.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153135"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145444744","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}
Pub Date : 2025-11-01DOI: 10.1016/j.imbio.2025.153139
Chunqiu Yang , Rui Qian , Mengtao Gong , Yizu Qin , Meijuan Zheng
Objectives
To evaluate the predictive value of NKG2A+ natural killer (NK) cells in identifying patients at risk of developing severe COVID-19 and assess the therapeutic potential of NKG2A blockade in restoring NK cell antiviral activity.
Methods
The association between NKG2A+ NK cells and clinical characteristics was assessed in Omicron-infected patients, and the diagnostic efficacy of NKG2A+ NK cell proportions was evaluated using ROC curves. Additionally, NKG2A blockade experiments were conducted in patients infected with the Wuhan strain.
Results
The proportion of NKG2A+ NK cells was significantly elevated in patients with severe COVID-19 caused by the Omicron variant, particularly among elderly individuals and those with multiple comorbidities. Integrating NKG2A+ NK cell proportions into a laboratory-based model significantly improved the predictive accuracy for severe COVID-19. Patients with NKG2A+ NK cell proportions ≥27 % exhibited lower lymphocyte counts and higher levels of NLR, D-dimer, CRP, LDH, and IL-6. Individuals within this high-NKG2A+ subgroup also had higher expression of inhibitory receptors (TIM3, TIGIT) and lower expression of activation markers (CD69, CD226, NKG2D), along with increased serum levels of TNF, IL-8, IL-10, and CCL5. Importantly, in Wuhan strain-infected patients, NKG2A blockade significantly restored NK cell activity, as shown by increased expression of activation markers NKG2D, CD69, and CD226, indicating a reversal of NK cell dysfunction.
Conclusions
NKG2A expression contributes to immunosuppression in COVID-19, with NKG2A+ NK cells serving as a diagnostic indicator of disease severity. A cut-off value of 27 % NKG2A+ NK cells may be clinically relevant for stratifying risk.
{"title":"Predictive value of NKG2A+ NK cell population in diagnosing severe COVID-19 patients","authors":"Chunqiu Yang , Rui Qian , Mengtao Gong , Yizu Qin , Meijuan Zheng","doi":"10.1016/j.imbio.2025.153139","DOIUrl":"10.1016/j.imbio.2025.153139","url":null,"abstract":"<div><h3>Objectives</h3><div>To evaluate the predictive value of NKG2A<sup>+</sup> natural killer (NK) cells in identifying patients at risk of developing severe COVID-19 and assess the therapeutic potential of NKG2A blockade in restoring NK cell antiviral activity.</div></div><div><h3>Methods</h3><div>The association between NKG2A<sup>+</sup> NK cells and clinical characteristics was assessed in Omicron-infected patients, and the diagnostic efficacy of NKG2A<sup>+</sup> NK cell proportions was evaluated using ROC curves. Additionally, NKG2A blockade experiments were conducted in patients infected with the Wuhan strain.</div></div><div><h3>Results</h3><div>The proportion of NKG2A<sup>+</sup> NK cells was significantly elevated in patients with severe COVID-19 caused by the Omicron variant, particularly among elderly individuals and those with multiple comorbidities. Integrating NKG2A<sup>+</sup> NK cell proportions into a laboratory-based model significantly improved the predictive accuracy for severe COVID-19. Patients with NKG2A<sup>+</sup> NK cell proportions ≥27 % exhibited lower lymphocyte counts and higher levels of NLR, D-dimer, CRP, LDH, and IL-6. Individuals within this high-NKG2A<sup>+</sup> subgroup also had higher expression of inhibitory receptors (TIM3, TIGIT) and lower expression of activation markers (CD69, CD226, NKG2D), along with increased serum levels of TNF, IL-8, IL-10, and CCL5. Importantly, in Wuhan strain-infected patients, NKG2A blockade significantly restored NK cell activity, as shown by increased expression of activation markers NKG2D, CD69, and CD226, indicating a reversal of NK cell dysfunction.</div></div><div><h3>Conclusions</h3><div>NKG2A expression contributes to immunosuppression in COVID-19, with NKG2A<sup>+</sup> NK cells serving as a diagnostic indicator of disease severity. A cut-off value of 27 % NKG2A<sup>+</sup> NK cells may be clinically relevant for stratifying risk.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153139"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145495379","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}
Background: Human BK polyomavirus (BKV) infection is a dangerous pathogenic factor in kidney transplant recipients (KTRs) due to the use of immunosuppressive drugs, which can cause damage to the transplanted kidneys after reactivation. BKV interacts with transcription factors that regulate the expression of genes involved in the immune system, which can cause kidney failure or transplant rejection due to tumorigenic antigens.
Methods: The genes mRNA expression levels of BKV, including large T antigen (LTA), small T antigen (STA), Agnoprotein, and viral structural proteins VP1, VP2, and VP3, as well as immune system transcription factors interferon regulatory factors 3 (IRF3), interferon regulatory factors 7 (IRF7), Toll-like receptor 7 (TLR7), and Toll-like receptor 8 (TLR8), were investigated using in-house Real-time PCR SYBR Green protocols.
Objective: The aim of this study was to investigate the effect of BKV reactivation on genes mRNA expression levels of viral genes and innate immune system factors including IRF3, IRF7, TLR7 and TLR8 and to determine the primary potential role of these factors during BKV pathogenesis by measuring genes mRNA expression levels in KTRs samples.
Results: The reactive group showed significant increase in the mRNA expression of viral genes. The increase in BKV replication potentially led to significantly decrease in mRNA expression levels of IRF3, IRF7, TLR7, and TLR8. In the latent group, the expression of IRF3 and IRF7 genes were significantly higher versus reactive group.
Conclusion: The results of analysis viral genes mRNA expression suggested potential role of viral genes during BKV pathogenesis. The results of this limited study showed that at the mRNA level, certain genes of the immune system can be altered and that BKV reactivation has the potential to affect these genes.
{"title":"Measuring mRNA expression level of viral genes, IRF3/7 and TLR7/8 during BK polyomavirus infection in kidney transplant recipients","authors":"Amin Zahmatkesh , Ramin Yaghobi , Ilnaz Sahragard , Afsoon Afshari , Seyed Younes Hosseini , Mohammad Kargar","doi":"10.1016/j.imbio.2025.153146","DOIUrl":"10.1016/j.imbio.2025.153146","url":null,"abstract":"<div><div><strong>Background</strong>: Human BK polyomavirus (BKV) infection is a dangerous pathogenic factor in kidney transplant recipients (KTRs) due to the use of immunosuppressive drugs, which can cause damage to the transplanted kidneys after reactivation. BKV interacts with transcription factors that regulate the expression of genes involved in the immune system, which can cause kidney failure or transplant rejection due to tumorigenic antigens.</div><div><strong>Methods</strong>: The genes mRNA expression levels of BKV, including large T antigen (LTA), small T antigen (STA), Agnoprotein, and viral structural proteins VP1, VP2, and VP3, as well as immune system transcription factors interferon regulatory factors 3 (IRF3), interferon regulatory factors 7 (IRF7), Toll-like receptor 7 (TLR7), and Toll-like receptor 8 (TLR8), were investigated using in-house Real-time PCR SYBR Green protocols.</div><div><strong>Objective</strong>: The aim of this study was to investigate the effect of BKV reactivation on genes mRNA expression levels of viral genes and innate immune system factors including IRF3, IRF7, TLR7 and TLR8 and to determine the primary potential role of these factors during BKV pathogenesis by measuring genes mRNA expression levels in KTRs samples.</div><div><strong>Results</strong>: The reactive group showed significant increase in the mRNA expression of viral genes. The increase in BKV replication potentially led to significantly decrease in mRNA expression levels of IRF3, IRF7, TLR7, and TLR8. In the latent group, the expression of IRF3 and IRF7 genes were significantly higher versus reactive group.</div><div><strong>Conclusion</strong>: The results of analysis viral genes mRNA expression suggested potential role of viral genes during BKV pathogenesis. The results of this limited study showed that at the mRNA level, certain genes of the immune system can be altered and that BKV reactivation has the potential to affect these genes.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153146"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677503","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}
Pub Date : 2025-11-01DOI: 10.1016/j.imbio.2025.153142
Evelyn Maciel de Oliveira , Camila Carvalho , Natalia Fonseca do Rosário , Carla Rodrigues , Iris Braga da Silva , Alice Ramos , Fabiana Rabe Carvalho , Pedro Barbosa , Fernanda G. De Felice , Mauro Jorge Cabral-Castro , Jocemir Ronaldo Lugon , Thalia Medeiros , Andrea Alice Silva
Introduction: We investigated circulating and urinary inflammatory mediators and extracellular vesicles (EVs) in association with clinical and laboratory findings during the post-COVID-19 (coronavirus disease 2019) period. Methods: A cross-sectional study was conducted with individuals with history of COVID-19 stratified according to the presence of post-COVID condition (PCC) and hospitalization during the acute phase. Circulating and urinary levels of 27 inflammatory mediators were quantified by multiplex assays. EVs were isolated by differential centrifugation and assessed by nanoscale flow cytometry, nanoparticle tracking analysis, and transmission electron microscopy. Results: We included 78 participants (55 ± 14.6 years-old, 79.5 % females), of whom 56 (71.8 %) had PCC. Of these, 18 (32 %) required hospitalization during COVID-19. No differences between groups were observed regarding plasma EVs, but hospitalized PCC patients presented lower levels of circulant interleukin (IL)-9 (p = 0.03), higher monocyte-to-lymphocyte ratio (p = 0.03), prothrombin time (p = 0.02), and lactate dehydrogenase (p = 0.01). In addition, higher levels of total urinary EVs (uEVs, p = 0.006) and uIL-4 (p = 0.01), chemokine (CC motif) ligand (CCL)-2 (p = 0.02), CCL-11 (p = 0.002), and granulocyte-macrophage colony-stimulating factor (p = 0.04) were observed in the same group. Likewise, individuals infected before vaccination presented higher total uEVs (p = 0.003) and urinary CCL-11 (p = 0.01), and multiple episodes of COVID-19 were associated with higher urinary interferon-γ (p = 0.04) and IL-1Ra (p = 0.03). Conclusion: Our results may suggest a possible remnant renal inflammatory process in PCC patients who had moderate-to-severe acute COVID-19.
{"title":"Higher levels of urinary extracellular vesicles and immune mediators are related to acute infection severity during the post-COVID period","authors":"Evelyn Maciel de Oliveira , Camila Carvalho , Natalia Fonseca do Rosário , Carla Rodrigues , Iris Braga da Silva , Alice Ramos , Fabiana Rabe Carvalho , Pedro Barbosa , Fernanda G. De Felice , Mauro Jorge Cabral-Castro , Jocemir Ronaldo Lugon , Thalia Medeiros , Andrea Alice Silva","doi":"10.1016/j.imbio.2025.153142","DOIUrl":"10.1016/j.imbio.2025.153142","url":null,"abstract":"<div><div><strong>Introduction:</strong> We investigated circulating and urinary inflammatory mediators and extracellular vesicles (EVs) in association with clinical and laboratory findings during the post-COVID-19 (coronavirus disease 2019) period. <strong>Methods:</strong> A cross-sectional study was conducted with individuals with history of COVID-19 stratified according to the presence of post-COVID condition (PCC) and hospitalization during the acute phase. Circulating and urinary levels of 27 inflammatory mediators were quantified by multiplex assays. EVs were isolated by differential centrifugation and assessed by nanoscale flow cytometry, nanoparticle tracking analysis, and transmission electron microscopy. <strong>Results:</strong> We included 78 participants (55 ± 14.6 years-old, 79.5 % females), of whom 56 (71.8 %) had PCC. Of these, 18 (32 %) required hospitalization during COVID-19. No differences between groups were observed regarding plasma EVs, but hospitalized PCC patients presented lower levels of circulant interleukin (IL)-9 (<em>p</em> = 0.03), higher monocyte-to-lymphocyte ratio (p = 0.03), prothrombin time (<em>p</em> = 0.02), and lactate dehydrogenase (<em>p</em> = 0.01). In addition, higher levels of total urinary EVs (uEVs, <em>p</em> = 0.006) and uIL-4 (p = 0.01), chemokine (C<img>C motif) ligand (CCL)-2 (p = 0.02), CCL-11 (<em>p</em> = 0.002), and granulocyte-macrophage colony-stimulating factor (<em>p</em> = 0.04) were observed in the same group. Likewise, individuals infected before vaccination presented higher total uEVs (<em>p</em> = 0.003) and urinary CCL-11 (<em>p</em> = 0.01), and multiple episodes of COVID-19 were associated with higher urinary interferon-γ (<em>p</em> = 0.04) and IL-1Ra (<em>p</em> = 0.03). <strong>Conclusion:</strong> Our results may suggest a possible remnant renal inflammatory process in PCC patients who had moderate-to-severe acute COVID-19.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153142"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145614741","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}
Pub Date : 2025-11-01DOI: 10.1016/j.imbio.2025.153120
Dalei Sun , Shu Ouyang , Xiaoxuan Xu , Jingjing Yan , Heqian Wang , Chenkai Lan , Wubin Ouyang , Liangjun Zhong , Jun Lin
{"title":"Corrigendum to “UMI-77 targets MCL-1 to activate mitophagy and ameliorate periodontitis in mice” [Immunobiology 230(5) (2025) 153108]","authors":"Dalei Sun , Shu Ouyang , Xiaoxuan Xu , Jingjing Yan , Heqian Wang , Chenkai Lan , Wubin Ouyang , Liangjun Zhong , Jun Lin","doi":"10.1016/j.imbio.2025.153120","DOIUrl":"10.1016/j.imbio.2025.153120","url":null,"abstract":"","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153120"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137317","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}
Pub Date : 2025-11-01DOI: 10.1016/j.imbio.2025.153140
Tomoaki Kamiya , Yuki Miyasaka , Hangsoo Kim , Sosuke Fukui , Masatoshi Inoue , Masatoshi Ishigami , Yasuhiro Suzuki , Shoichi Maruyama , Tamio Ohno , Timothy R. Hughes , B. Paul Morgan , Masashi Mizuno
Background
Malaria is an important and serious parasite-induced disease associated with severe anemia and multiple organ failure (MOF) that can be lethal in humans. We explored the contribution of the terminal pathway of complement in a mouse model of malaria-induced lethal MOF following infection with Plasmodium (P.) bergei.
Methods
We compared organ damage and survival between C57BL/6 J mice deficient in the terminal pathway component C6 (C6def) and wild type C57BL/6 J mice (WT) after intraperitoneal injection of 106P. bergei-parasitized erythrocytes. We measured survival, relevant blood parameters, assessed severity of injury and complement activation in relevant organs.
Results
All WT mice died between 7 and 13 days after exposure to the parasite challenge; in contrast, C6def mice showed prolonged survival with 80 % alive at day 20, although all then died by day 26. Parasite load and anemia at day 7 were similar in C6def and WT mice. Liver and lung injuries, fibrosis and organ complement deposition assessed at day 7 post-infection were significantly milder in C6def mice compared to WT. Blood platelet count at day 7 post-infection was markedly reduced in WT but not in C6def mice; in contrast, white cell count was increased and hemoglobin levels decreased to similar degrees in WT and C6def mice post-infection. Albumin levels were reduced, significantly more in WT, while blood markers of liver injury were increased, significantly more in WT. Serum levels of complement activation product, C5a, and IL6 were increased in both groups, the latter significantly higher in WT versus C6def mice.
Conclusion
We show that complement terminal pathway activation exacerbates organ injuries and thrombocytopenia associated with P. bergei infection, contributing to rapid progression to death in the model. Inhibition of terminal pathway activation in human malarial infections using available drugs might slow progression to organ failure, extending the window of opportunity for the effective use of anti-malarial medicines.
{"title":"Absence of complement terminal pathway activity in C6-deficient mice prolongs survival in a mouse model of severe malarial infection","authors":"Tomoaki Kamiya , Yuki Miyasaka , Hangsoo Kim , Sosuke Fukui , Masatoshi Inoue , Masatoshi Ishigami , Yasuhiro Suzuki , Shoichi Maruyama , Tamio Ohno , Timothy R. Hughes , B. Paul Morgan , Masashi Mizuno","doi":"10.1016/j.imbio.2025.153140","DOIUrl":"10.1016/j.imbio.2025.153140","url":null,"abstract":"<div><h3>Background</h3><div>Malaria is an important and serious parasite-induced disease associated with severe anemia and multiple organ failure (MOF) that can be lethal in humans. We explored the contribution of the terminal pathway of complement in a mouse model of malaria-induced lethal MOF following infection with <em>Plasmodium</em> (<em>P.</em>) <em>bergei</em>.</div></div><div><h3>Methods</h3><div>We compared organ damage and survival between C57BL/6 J mice deficient in the terminal pathway component C6 (C6def) and wild type C57BL/6 J mice (WT) after intraperitoneal injection of 10<sup>6</sup> <em>P. bergei</em>-parasitized erythrocytes. We measured survival, relevant blood parameters, assessed severity of injury and complement activation in relevant organs.</div></div><div><h3>Results</h3><div>All WT mice died between 7 and 13 days after exposure to the parasite challenge; in contrast, C6def mice showed prolonged survival with 80 % alive at day 20, although all then died by day 26. Parasite load and anemia at day 7 were similar in C6def and WT mice. Liver and lung injuries, fibrosis and organ complement deposition assessed at day 7 post-infection were significantly milder in C6def mice compared to WT. Blood platelet count at day 7 post-infection was markedly reduced in WT but not in C6def mice; in contrast, white cell count was increased and hemoglobin levels decreased to similar degrees in WT and C6def mice post-infection. Albumin levels were reduced, significantly more in WT, while blood markers of liver injury were increased, significantly more in WT. Serum levels of complement activation product, C5a, and IL6 were increased in both groups, the latter significantly higher in WT <em>versus</em> C6def mice.</div></div><div><h3>Conclusion</h3><div>We show that complement terminal pathway activation exacerbates organ injuries and thrombocytopenia associated with <em>P. bergei</em> infection, contributing to rapid progression to death in the model. Inhibition of terminal pathway activation in human malarial infections using available drugs might slow progression to organ failure, extending the window of opportunity for the effective use of anti-malarial medicines.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153140"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145540639","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}
The ability of Natural Killer (NK) cells, to generate memory-like responses against viruses including – HIV, opened up possibility of their application as immune therapy. We attempted to generate memory-like NK cells from HIV exposed and unexposed primary NK cells. The PBMCs of HIV uninfected and infected individuals (LTNPs, ART experienced and with progressive disease) were preactivated with cytokine cocktail (CC) of IL12, IL 15 and IL 18 with or without HIV-1 Env C or only IL 15 and restimulated with CC + HIV-1 Env C after seven days' rest. The CD56+ NK cells from the cultures were assessed for IFN-γ, TNF-α, and perforin secretion and expression of CD107a using multiparametric flow cytometry. Higher functionality was observed in case of pre-activation with CC with or without HIV-1 Env C as compared to only Il 15 across study groups. However, the functionality of the generated memory -like NK cells was significantly higher in case of LTNPs and the ART experienced individuals only. Low frequency of functional NK cells generated from HIV unexposed NK cells indicate probable specificity to HIV. The memory-like NK cells from ART experienced individuals generated after CC and CC+ HIV-1C preactivation showed good proliferating ability and also an ability to lyse the allogenic HIV infected CD4+ T cells. This work highlighted that HIV specific memory-like NK cells can be generated from the NK cells of HIV infected individuals with robust immune status after pre-activation with cytokine cocktail with or without HIV-1C. Although preliminary, these findings suggest that memory-like NK cells could have potential for use in immunotherapy aimed at clearing viral reservoirs.
{"title":"Anti-retroviral treatment of HIV infected individuals improves the ex vivo generation of memory-like NK cells","authors":"Kalavati Lalsare MSc, Shubhangi Bichare MSc, Sheetal Mulay MSc, Rajani D. Bagul MSW, Suvarna Sane M.Phil, Madhuri Thakar PhD","doi":"10.1016/j.imbio.2025.153127","DOIUrl":"10.1016/j.imbio.2025.153127","url":null,"abstract":"<div><div>The ability of Natural Killer (NK) cells, to generate memory-like responses against viruses including – HIV, opened up possibility of their application as immune therapy. We attempted to generate memory-like NK cells from HIV exposed and unexposed primary NK cells. The PBMCs of HIV uninfected and infected individuals (LTNPs, ART experienced and with progressive disease) were preactivated with cytokine cocktail (CC) of IL12, IL 15 and IL 18 with or without HIV-1 Env C or only IL 15 and restimulated with CC + HIV-1 Env C after seven days' rest. The CD56+ NK cells from the cultures were assessed for IFN-γ, TNF-α, and perforin secretion and expression of CD107a using multiparametric flow cytometry. Higher functionality was observed in case of pre-activation with CC with or without HIV-1 Env C as compared to only Il 15 across study groups. However, the functionality of the generated memory -like NK cells was significantly higher in case of LTNPs and the ART experienced individuals only. Low frequency of functional NK cells generated from HIV unexposed NK cells indicate probable specificity to HIV. The memory-like NK cells from ART experienced individuals generated after CC and CC+ HIV-1C preactivation showed good proliferating ability and also an ability to lyse the allogenic HIV infected CD4+ T cells. This work highlighted that HIV specific memory-like NK cells can be generated from the NK cells of HIV infected individuals with robust immune status after pre-activation with cytokine cocktail with or without HIV-1C. Although preliminary, these findings suggest that memory-like NK cells could have potential for use in immunotherapy aimed at clearing viral reservoirs.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153127"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145408872","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}
Colorectal cancer (CRC) requires effective preventive measures due to its high prevalence, mortality rate, and impact on patients' lives. Therefore, this study aimed to assess the immunomodulatory effects of α-tocopherol (α-TOC) within the tumor microenvironment (TME) of CRC using a co-culture model.
Methods
To characterize the biological effects of vitamin E, apoptosis assays, scratch tests, and real-time PCR were performed to investigate the direct effect of α-TOC (2.2, 22, and 220 μM) on the viability, migration, and pathway mechanisms of the SW480 CRC cell line. PBMCs (peripheral blood mononuclear cells) were co-cultured with the SW480 to assess the effects within the TME and then treated with α-TOC. We evaluated the effect of α-TOC on the viability of PBMC and the co-culture of PBMC+SW480 using an MTT assay. Additionally, we performed ELISA and flow cytometry to assess the effect of α-TOC on the secretion of IFN-γ and the population of immunomodulatory cells such as MDSCs and Treg cells, respectively.
Results
Our findings revealed that α-TOC significantly induced apoptosis in SW480 cells and promoted the proliferation of PBMCs (P < 0.05). In the co-culture group (PBMC+SW480), α-TOC stimulated PBMC proliferation, increased IFN-γ secretion, and reduced the population of MDSCs (P < 0.05). However, α-TOC did not significantly affect the Treg population.
Conclusion
These results suggest that, in addition to its direct anti-tumor effects, α-TOC also shows immunomodulatory properties in the context of colon cancer in an in vitro model.
{"title":"The anti-tumor and immunomodulatory effect of α-tocopherol on tumor microenvironment in an in vitro model of colon cancer","authors":"Tahereh Azari , Fatemeh Sadeghi , Kosar Malekpour , Farzad Nasri , Elahe Safari","doi":"10.1016/j.imbio.2025.153138","DOIUrl":"10.1016/j.imbio.2025.153138","url":null,"abstract":"<div><h3>Background</h3><div>Colorectal cancer (CRC) requires effective preventive measures due to its high prevalence, mortality rate, and impact on patients' lives. Therefore, this study aimed to assess the immunomodulatory effects of α-tocopherol (α-TOC) within the tumor microenvironment (TME) of CRC using a co-culture model.</div></div><div><h3>Methods</h3><div>To characterize the biological effects of vitamin E, apoptosis assays, scratch tests, and real-time PCR were performed to investigate the direct effect of α-TOC (2.2, 22, and 220 μM) on the viability, migration, and pathway mechanisms of the SW480 CRC cell line. PBMCs (peripheral blood mononuclear cells) were co-cultured with the SW480 to assess the effects within the TME and then treated with α-TOC. We evaluated the effect of α-TOC on the viability of PBMC and the co-culture of PBMC+SW480 using an MTT assay. Additionally, we performed ELISA and flow cytometry to assess the effect of α-TOC on the secretion of IFN-γ and the population of immunomodulatory cells such as MDSCs and Treg cells, respectively.</div></div><div><h3>Results</h3><div>Our findings revealed that α-TOC significantly induced apoptosis in SW480 cells and promoted the proliferation of PBMCs (<em>P</em> < 0.05). In the co-culture group (PBMC+SW480), α-TOC stimulated PBMC proliferation, increased IFN-γ secretion, and reduced the population of MDSCs (<em>P</em> < 0.05). However, α-TOC did not significantly affect the Treg population<strong>.</strong></div></div><div><h3>Conclusion</h3><div>These results suggest that, in addition to its direct anti-tumor effects, α-TOC also shows immunomodulatory properties in the context of colon cancer in an <em>in vitro</em> model.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153138"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145512641","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}
Pub Date : 2025-11-01DOI: 10.1016/j.imbio.2025.153137
Ping Jiang , Daxi Ma , Youji Jia , Honghong Ma , Yajuan Guo , Juhua Zhang , Wei Yan , Xiaobing Xi
Objective
This study aims to investigate the role of the WNT5A signaling pathway in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) and uncover the impact of WNT5A on cellular function and signal transduction through proteomic and phosphoproteomic analyses.
Methods
MH7A cells were treated with recombinant WNT5A (rhWNT5A), and differential expression proteins (DEPs) and phosphoproteins (DEPPs) were identified through proteomic and phosphoproteomic analyses. Data were further analyzed via volcano plots, heatmaps, enrichment analysis, and protein-protein interaction (PPI) networks to identify key biological processes and signaling pathways regulated by WNT5A.
Results
Significant changes in the expression of numerous DEPs and DEPPs were observed following rhWNT5A treatment, including proteins closely related to lipid metabolism, cell migration, inflammation, and cell proliferation. PPI network analysis revealed that key regulatory proteins, such as HNRNPA1, RANBP2, BCLAF1, NPM1, and SMARCA4, occupy central positions in the network. Enrichment analysis indicated that WNT5A influences essential signaling pathways, such as AMPK, mTOR, VEGFA-VEGFR2, Notch, and endoplasmic reticulum stress, regulating cellular energy metabolism, inflammatory response, and cytoskeletal remodeling. Kinase activity analysis identified significant changes in kinases such as CDK1, CSNK2A1, EEF2K, AURKA, and AURKB, which were further integrated into the kinase-substrate regulatory network.
Conclusion
This study demonstrates that WNT5A significantly influences the biological functions and inflammatory responses of RA-FLS by regulating key biological processes and signaling pathways. The integrated proteomic and phosphoproteomic analyses provide insights into the potential mechanisms and regulatory networks of WNT5A in RA, suggesting its application as a potential therapeutic target.
{"title":"The Role of WNT5A-mediated proteomic and phosphoproteomic regulatory networks in rheumatoid arthritis","authors":"Ping Jiang , Daxi Ma , Youji Jia , Honghong Ma , Yajuan Guo , Juhua Zhang , Wei Yan , Xiaobing Xi","doi":"10.1016/j.imbio.2025.153137","DOIUrl":"10.1016/j.imbio.2025.153137","url":null,"abstract":"<div><h3>Objective</h3><div>This study aims to investigate the role of the <em>WNT5A</em> signaling pathway in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) and uncover the impact of <em>WNT5A</em> on cellular function and signal transduction through proteomic and phosphoproteomic analyses.</div></div><div><h3>Methods</h3><div>MH7A cells were treated with recombinant <em>WNT5A</em> (rhWNT5A), and differential expression proteins (DEPs) and phosphoproteins (DEPPs) were identified through proteomic and phosphoproteomic analyses. Data were further analyzed via volcano plots, heatmaps, enrichment analysis, and protein-protein interaction (PPI) networks to identify key biological processes and signaling pathways regulated by <em>WNT5A.</em></div></div><div><h3>Results</h3><div>Significant changes in the expression of numerous DEPs and DEPPs were observed following rhWNT5A treatment, including proteins closely related to lipid metabolism, cell migration, inflammation, and cell proliferation. PPI network analysis revealed that key regulatory proteins, such as <em>HNRNPA1</em>, <em>RANBP2</em>, <em>BCLAF1</em>, <em>NPM1</em>, and <em>SMARCA4</em>, occupy central positions in the network. Enrichment analysis indicated that <em>WNT5A</em> influences essential signaling pathways, such as <em>AMPK</em>, <em>mTOR</em>, <em>VEGFA-VEGFR2</em>, Notch, and endoplasmic reticulum stress, regulating cellular energy metabolism, inflammatory response, and cytoskeletal remodeling. Kinase activity analysis identified significant changes in kinases such as <em>CDK1</em>, <em>CSNK2A1</em>, <em>EEF2K</em>, <em>AURKA</em>, and <em>AURKB</em>, which were further integrated into the kinase-substrate regulatory network.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that <em>WNT5A</em> significantly influences the biological functions and inflammatory responses of RA-FLS by regulating key biological processes and signaling pathways. The integrated proteomic and phosphoproteomic analyses provide insights into the potential mechanisms and regulatory networks of <em>WNT5A</em> in RA, suggesting its application as a potential therapeutic target.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153137"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145516874","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}
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