Pub Date : 2025-09-01DOI: 10.1016/j.imbio.2025.153111
Haixiang Zhang , Jingying Sun , Chunyan Guo , Cuixiang Xu , Jun Hu
Autoimmune diseases (AID) are chronic debilitating diseases characterized by excessive or prolonged autoimmune responses, which lead to the destruction of normal tissue structures and consequent clinical symptoms. AID poses a significant threat to human health, and its pathogenic mechanism remains poorly understood. Etiological studies suggest that the onset of AID primarily caused by the combined influence of environmental and genetic factors. The development of stable and effective animal models is a crucial approach and method for studying the pathogenesis of AID and for accurate prevention and treatment. This paper presents a review of the classification of immune antigens, heterophilic antigen epitopes, and the role of autoantigens in the construction of AID animal models, focusing particularly on the establishment of antigen-induced AID animal models, aiming to provide theoretical references for subsequent research on AID.
{"title":"Research progress of animal models of antigen-induced autoimmune diseases","authors":"Haixiang Zhang , Jingying Sun , Chunyan Guo , Cuixiang Xu , Jun Hu","doi":"10.1016/j.imbio.2025.153111","DOIUrl":"10.1016/j.imbio.2025.153111","url":null,"abstract":"<div><div>Autoimmune diseases (AID) are chronic debilitating diseases characterized by excessive or prolonged autoimmune responses, which lead to the destruction of normal tissue structures and consequent clinical symptoms. AID poses a significant threat to human health, and its pathogenic mechanism remains poorly understood. Etiological studies suggest that the onset of AID primarily caused by the combined influence of environmental and genetic factors. The development of stable and effective animal models is a crucial approach and method for studying the pathogenesis of AID and for accurate prevention and treatment. This paper presents a review of the classification of immune antigens, heterophilic antigen epitopes, and the role of autoantigens in the construction of AID animal models, focusing particularly on the establishment of antigen-induced AID animal models, aiming to provide theoretical references for subsequent research on AID.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 5","pages":"Article 153111"},"PeriodicalIF":2.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144926157","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 : 2025-08-29DOI: 10.1016/j.imbio.2025.153112
Jinxia Ma, Lipei Shao, Tatyana Fuksenko, Hui Liu, Chunjie Jiang, Yihua Cai, Yong Soo Kim, Kathryn Martin, Larry Moses, Nan Zhang, Anh Dinh, Robert P. Somerville, David F. Stroncek, Ping Jin
Background
Hematopoietic progenitor cells (HPCs) and mononuclear cells (MNCs) are critical components of cell-based therapies, including bone marrow transplantation and regenerative treatments. Evaluation of the characteristics of these products during collection, storage, and transport is essential for maintaining cell viability and functionality. In this study, we evaluated the functional and molecular stability of samples collected for the evaluation of fresh HPC and MNC products. The samples stored at 4 °C for up to 4 days and were evaluated using white blood cell (WBC) counts, flow cytometry, and bulk RNA sequencing (RNA-seq) across five time points.
Methods
HPC samples from seven products (June–December 2022) and MNC samples from six products (October 2022–August 2023) were analyzed on days 0 through 4 after collection. WBC counts were measured, and viability was assessed using 7-AAD staining and flow cytometry. HPC samples were stained with antibodies against CD34, CD3, CD19, CD56, CD14, CD16, CD15, and CD45, while MNC samples were stained with antibodies directed to CD3, CD4, CD8, CD19, CD56, CD14, CD16, CD15, and CD45. Total RNA was isolated from each sample and subjected to bulk RNA-seq to assess transcriptomic changes during storage.
Results
While WBC counts varied between products, no significant differences were observed across time points within individual products. Flow cytometry markers remained relatively stable over time in both HPC and MNC samples, although greater variability was observed in HPCs. A modest decrease in lymphocyte percentages was noted at later time points, primarily driven by a reduction in CD3+ cells; however, these changes were not statistically significant. Cell viability declined significantly over time within individual products and showed inter-product variability. RNA-seq analysis revealed stable gene expression profiles in MNC samples across all time points. In contrast, HPC samples exhibited notable transcriptomic changes as early as day 1 of storage at 4 °C, indicating greater molecular instability.
Conclusion
WBC counts and flow cytometry markers remain stable for up to 3 days in samples collected from fresh HPC and MNC products when stored at 4 °C, although cell viability progressively declines. However, RNA-seq data reveal early transcriptomic changes in HPC samples, suggesting that immediate evaluation of these samples is critical to preserve their molecular integrity and functionality. These findings support the feasibility of delayed phenotypic analysis but emphasize the need for prompt molecular assays in HPC-based applications.
{"title":"Stability testing of HPCs and MNCs from apheresis products","authors":"Jinxia Ma, Lipei Shao, Tatyana Fuksenko, Hui Liu, Chunjie Jiang, Yihua Cai, Yong Soo Kim, Kathryn Martin, Larry Moses, Nan Zhang, Anh Dinh, Robert P. Somerville, David F. Stroncek, Ping Jin","doi":"10.1016/j.imbio.2025.153112","DOIUrl":"10.1016/j.imbio.2025.153112","url":null,"abstract":"<div><h3>Background</h3><div>Hematopoietic progenitor cells (HPCs) and mononuclear cells (MNCs) are critical components of cell-based therapies, including bone marrow transplantation and regenerative treatments. Evaluation of the characteristics of these products during collection, storage, and transport is essential for maintaining cell viability and functionality. In this study, we evaluated the functional and molecular stability of samples collected for the evaluation of fresh HPC and MNC products. The samples stored at 4 °C for up to 4 days and were evaluated using white blood cell (WBC) counts, flow cytometry, and bulk RNA sequencing (RNA-seq) across five time points.</div></div><div><h3>Methods</h3><div>HPC samples from seven products (June–December 2022) and MNC samples from six products (October 2022–August 2023) were analyzed on days 0 through 4 after collection. WBC counts were measured, and viability was assessed using 7-AAD staining and flow cytometry. HPC samples were stained with antibodies against CD34, CD3, CD19, CD56, CD14, CD16, CD15, and CD45, while MNC samples were stained with antibodies directed to CD3, CD4, CD8, CD19, CD56, CD14, CD16, CD15, and CD45. Total RNA was isolated from each sample and subjected to bulk RNA-seq to assess transcriptomic changes during storage.</div></div><div><h3>Results</h3><div>While WBC counts varied between products, no significant differences were observed across time points within individual products. Flow cytometry markers remained relatively stable over time in both HPC and MNC samples, although greater variability was observed in HPCs. A modest decrease in lymphocyte percentages was noted at later time points, primarily driven by a reduction in CD3+ cells; however, these changes were not statistically significant. Cell viability declined significantly over time within individual products and showed inter-product variability. RNA-seq analysis revealed stable gene expression profiles in MNC samples across all time points. In contrast, HPC samples exhibited notable transcriptomic changes as early as day 1 of storage at 4 °C, indicating greater molecular instability.</div></div><div><h3>Conclusion</h3><div>WBC counts and flow cytometry markers remain stable for up to 3 days in samples collected from fresh HPC and MNC products when stored at 4 °C, although cell viability progressively declines. However, RNA-seq data reveal early transcriptomic changes in HPC samples, suggesting that immediate evaluation of these samples is critical to preserve their molecular integrity and functionality. These findings support the feasibility of delayed phenotypic analysis but emphasize the need for prompt molecular assays in HPC-based applications.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153112"},"PeriodicalIF":2.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005236","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 : 2025-08-21DOI: 10.1016/j.imbio.2025.153109
Yueming Liang , Danqi Sun , Qizhi Xu , Xiaofan Mao , Minjing Li , XingLin Gao , Sifei Yu
Background
The increasing interest in the roles of B cells, particularly regulatory B cells, within the tumor microenvironment has become prominent, though their immunological characteristics in malignant pleural effusions (PE) remain poorly elucidated.
Methods
Flow cytometry was performed in 143 pleural effusion and peripheral blood samples from patients in order to analyze the proportions of PB-derived B and T cells, and to assess surface markers and cytokines, such as IFN-γ and IL-10. Moreover, we compared clinical role of CD24+CD27+ B cell populations.
Results
B cell populations were significantly higher in PE from lung adenocarcinoma (LUAD) than tuberculosis (TB). Compared to PB from patients, the proportion of CD24+CD27+ B cells was markedly elevated in LUAD-PE and exhibited reduced levels of CD38, CD5, CD71, PD-1, and PD-L1, as well as an upregulation of IL-10 and CD39. PD-1 and PD-L1 were largely found to be upregulated within the CD27+CD38+ B cell subset despite declining proportions overall. Re-interpretations illustrated significant relationships between CD24+CD27+ B cells and clinical measurements.
Conclusions
This study highlights the heterogenic phenotypes and functions of various B cell subsets in LUAD-PE, with specific attention to CD24+CD27+ B cells as potential diagnostic markers and the need for further studies investigating their immunoregulatory functions to unveil new immunotherapeutic strategies in lung cancer.
{"title":"Increase CD24+CD27+ B cells within pleural effusions derived from lung adenocarcinoma presents enhanced potential for clinical utility","authors":"Yueming Liang , Danqi Sun , Qizhi Xu , Xiaofan Mao , Minjing Li , XingLin Gao , Sifei Yu","doi":"10.1016/j.imbio.2025.153109","DOIUrl":"10.1016/j.imbio.2025.153109","url":null,"abstract":"<div><h3>Background</h3><div>The increasing interest in the roles of B cells, particularly regulatory B cells, within the tumor microenvironment has become prominent, though their immunological characteristics in malignant pleural effusions (PE) remain poorly elucidated.</div></div><div><h3>Methods</h3><div>Flow cytometry was performed in 143 pleural effusion and peripheral blood samples from patients in order to analyze the proportions of<!--> <!-->PB-derived B and T cells, and to assess surface markers and cytokines, such as IFN-γ and IL-10. Moreover, we compared clinical role of CD24<sup>+</sup>CD27<sup>+</sup> <!-->B cell populations.</div></div><div><h3>Results</h3><div>B cell populations were significantly higher in PE from lung adenocarcinoma (LUAD)<!--> <!-->than tuberculosis (TB). Compared to PB from patients, the proportion of CD24<sup>+</sup>CD27<sup>+</sup> B cells was markedly elevated in LUAD-PE and exhibited reduced levels of CD38, CD5, CD71,<!--> <!-->PD-1, and PD-L1, as well as an upregulation of IL-10 and CD39. PD-1 and PD-L1 were<!--> <!-->largely found to be upregulated within the CD27<sup>+</sup>CD38<sup>+</sup> B cell subset despite declining proportions overall. <em>Re</em>-interpretations illustrated significant relationships<!--> <!-->between CD24<sup>+</sup>CD27<sup>+</sup> B cells and clinical measurements.</div></div><div><h3>Conclusions</h3><div>This study highlights the heterogenic<!--> <!-->phenotypes and functions of various B cell subsets in LUAD-PE, with specific attention to CD24<sup>+</sup>CD27<sup>+</sup> B cells as potential diagnostic markers and the need for further studies investigating their immunoregulatory functions to unveil new immunotherapeutic strategies in lung cancer.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 5","pages":"Article 153109"},"PeriodicalIF":2.3,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144904225","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 : 2025-08-16DOI: 10.1016/j.imbio.2025.153108
Dalei Sun , Shu Ouyang , Xiaoxuan Xu , Jingjing Yan , Heqian Wang , Chenkai Lan , Wubin Ouyang , Liangjun Zhong , Jun Lin
<div><h3>Objective</h3><div>To investigate the therapeutic and ameliorative effects of the Myeloid Cell Leukemia 1 protein (MCL-1) inhibitor UMI-77 on experimental murine periodontitis via mitophagy activation, with a focus on comparing administration routes (local/intraperitoneal) and doses (high/low/combined).</div></div><div><h3>Methods</h3><div>A ligature-induced periodontitis model was established in 54 male C57BL/6 J mice, randomized into 9 groups (<em>n</em> = 6 per group): normal control (Group Aa), periodontitis model (Group Ab), positive control (Group Ac, local minocycline), local PBS control (Group Ad), intraperitoneal PBS control (Group Ae), local high-dose UMI-77 (Group Ba, 2 mg/kg), local low-dose UMI-77 (Group Bb, 1 mg/kg), intraperitoneal UMI-77 (Group Ca, 2 mg/kg), and combined intraperitoneal UMI-77 + local minocycline (Group Cb, 2 mg/kg + standard minocycline regimen). Outcomes included periodontal bleeding on probing (BOP), alveolar bone resorption via micro-CT, histopathological analysis (HE/methylene blue staining), MCL-1 expression (Western blot), autolysosome detection (transmission electron microscopy, TEM), and systemic organ safety (HE staining).</div></div><div><h3>Results</h3><div>All UMI-77 treatment groups exhibited significant amelioration of periodontal inflammation and bone resorption compared to the model group (Ab, <em>p</em> < 0.0001). Local high-dose UMI-77 (Group Ba) demonstrated the most potent efficacy, reducing BOP by 76 % (0.67 ± 0.5 vs. Ab: 2.8 ± 0.4, <em>p</em> < 0.001) and cementoenamel junction–alveolar bone crest distance by 48.7 % (0.20 ± 0.04 mm vs. Ab: 0.41 ± 0.05 mm, <em>p</em> < 0.0001), outperforming the positive control (Group Ac, BOP: 2.17 ± 0.4, <em>p</em> < 0.001). Histological analysis showed reduced inflammatory cell infiltration and organized periodontal fibers in Group Ba. Western blot confirmed downregulation of MCL-1 expression to near-normal levels in Group Ba, while TEM detected autolysosomes in both Group Ba and Group Ca, indicating mitophagy activation. Systemic safety assessments revealed only mild grade 1 cardiac septal thickening in Group Ba and transient splenic lymphocyte elevation in Group Ca, with no severe organ toxicity.</div></div><div><h3>Conclusion</h3><div>UMI-77 exerts significant therapeutic and ameliorative effects against periodontitis in mice, with local high-dose administration (Group Ba) demonstrating optimal efficacy. Intraperitoneal UMI-77 combined with local minocycline (Group Cb) achieved comparable outcomes to high-dose local UMI-77, highlighting potential combinatorial strategies. These findings establish UMI-77 as a promising agent for periodontitis treatment via MCL-1-targeted mitophagy activation.</div></div><div><h3>Clinical significance</h3><div>UMI-77, especially with local high-dose administration, offers a new, potentially effective and safe approach for periodontitis treatment, holding great promise for clinical translation.</div></
{"title":"UMI-77 targets MCL-1 to activate mitophagy and ameliorate periodontitis in mice","authors":"Dalei Sun , Shu Ouyang , Xiaoxuan Xu , Jingjing Yan , Heqian Wang , Chenkai Lan , Wubin Ouyang , Liangjun Zhong , Jun Lin","doi":"10.1016/j.imbio.2025.153108","DOIUrl":"10.1016/j.imbio.2025.153108","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the therapeutic and ameliorative effects of the Myeloid Cell Leukemia 1 protein (MCL-1) inhibitor UMI-77 on experimental murine periodontitis via mitophagy activation, with a focus on comparing administration routes (local/intraperitoneal) and doses (high/low/combined).</div></div><div><h3>Methods</h3><div>A ligature-induced periodontitis model was established in 54 male C57BL/6 J mice, randomized into 9 groups (<em>n</em> = 6 per group): normal control (Group Aa), periodontitis model (Group Ab), positive control (Group Ac, local minocycline), local PBS control (Group Ad), intraperitoneal PBS control (Group Ae), local high-dose UMI-77 (Group Ba, 2 mg/kg), local low-dose UMI-77 (Group Bb, 1 mg/kg), intraperitoneal UMI-77 (Group Ca, 2 mg/kg), and combined intraperitoneal UMI-77 + local minocycline (Group Cb, 2 mg/kg + standard minocycline regimen). Outcomes included periodontal bleeding on probing (BOP), alveolar bone resorption via micro-CT, histopathological analysis (HE/methylene blue staining), MCL-1 expression (Western blot), autolysosome detection (transmission electron microscopy, TEM), and systemic organ safety (HE staining).</div></div><div><h3>Results</h3><div>All UMI-77 treatment groups exhibited significant amelioration of periodontal inflammation and bone resorption compared to the model group (Ab, <em>p</em> < 0.0001). Local high-dose UMI-77 (Group Ba) demonstrated the most potent efficacy, reducing BOP by 76 % (0.67 ± 0.5 vs. Ab: 2.8 ± 0.4, <em>p</em> < 0.001) and cementoenamel junction–alveolar bone crest distance by 48.7 % (0.20 ± 0.04 mm vs. Ab: 0.41 ± 0.05 mm, <em>p</em> < 0.0001), outperforming the positive control (Group Ac, BOP: 2.17 ± 0.4, <em>p</em> < 0.001). Histological analysis showed reduced inflammatory cell infiltration and organized periodontal fibers in Group Ba. Western blot confirmed downregulation of MCL-1 expression to near-normal levels in Group Ba, while TEM detected autolysosomes in both Group Ba and Group Ca, indicating mitophagy activation. Systemic safety assessments revealed only mild grade 1 cardiac septal thickening in Group Ba and transient splenic lymphocyte elevation in Group Ca, with no severe organ toxicity.</div></div><div><h3>Conclusion</h3><div>UMI-77 exerts significant therapeutic and ameliorative effects against periodontitis in mice, with local high-dose administration (Group Ba) demonstrating optimal efficacy. Intraperitoneal UMI-77 combined with local minocycline (Group Cb) achieved comparable outcomes to high-dose local UMI-77, highlighting potential combinatorial strategies. These findings establish UMI-77 as a promising agent for periodontitis treatment via MCL-1-targeted mitophagy activation.</div></div><div><h3>Clinical significance</h3><div>UMI-77, especially with local high-dose administration, offers a new, potentially effective and safe approach for periodontitis treatment, holding great promise for clinical translation.</div></","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 5","pages":"Article 153108"},"PeriodicalIF":2.3,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144890277","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 abnormal quantity and dysfunction of immune cells in patients with multiple myeloma impede anti-tumour immunity and prompt the occurrence and development of disease. It has been reported that CD38+ NK cells are involved in immune regulation.
Methods
Peripheral blood (PB) samples were collected from healthy volunteers (HV) and newly diagnosed multiple myeloma (NDMM) patients. The proportions of CD38+ NK cells and CD38+CD16+ NK cells were measured. Moreover, CD38+ NK cells separated from PB were co-cultured with RPMI-8226 assess their impact on myeloma cell apoptosis and proliferation. Similar co-culture experiments were also initiated with naive CD4+ T cells from HV to ascertain the influence of CD38+ NK cells on regulatory T cells (Tregs) differentiation.
Results
The percentages of CD38+ NK and CD38+CD16+ NK cells in the PB of NDMM patients were markedly decrease than that in HV. The apoptosis rate of RPMI-8226 was slightly increased following co-culture with CD38+ NK cells from NDMM samples, as opposed to those from HV samples. CD38+ NK cells from NDMM or HV had similar inhibitory effect on MM cell proliferation. Furthermore, CD38+ NK cells from NDMM fostered CD4+ T cell differentiation to Tregs more than those from HV.
Conclusion
In MM, the proportion and function of CD38+ NK cells undergo changes, which may be related to the formation of the immunosuppressive microenvironment.
{"title":"Proportional and functional anomalies of CD38+ NK Cells:A new mechanism for impaired anti-tumour immunity in multiple myeloma?","authors":"Huixian Chen , Kehua Fang , Jinbao Zong , Xiaotian Chang","doi":"10.1016/j.imbio.2025.153107","DOIUrl":"10.1016/j.imbio.2025.153107","url":null,"abstract":"<div><h3>Background</h3><div>The abnormal quantity and dysfunction of immune cells in patients with multiple myeloma impede anti-tumour immunity and prompt the occurrence and development of disease. It has been reported that CD38<sup>+</sup> NK cells are involved in immune regulation.</div></div><div><h3>Methods</h3><div>Peripheral blood (PB) samples were collected from healthy volunteers (HV) and newly diagnosed multiple myeloma (NDMM) patients. The proportions of CD38<sup>+</sup> NK cells and CD38<sup>+</sup>CD16<sup>+</sup> NK cells were measured. Moreover, CD38<sup>+</sup> NK cells separated from PB were co-cultured with RPMI-8226 assess their impact on myeloma cell apoptosis and proliferation. Similar co-culture experiments were also initiated with naive CD4<sup>+</sup> T cells from HV to ascertain the influence of CD38<sup>+</sup> NK cells on regulatory T cells (Tregs) differentiation.</div></div><div><h3>Results</h3><div>The percentages of CD38<sup>+</sup> NK and CD38<sup>+</sup>CD16<sup>+</sup> NK cells in the PB of NDMM patients were markedly decrease than that in HV. The apoptosis rate of RPMI-8226 was slightly increased following co-culture with CD38<sup>+</sup> NK cells from NDMM samples, as opposed to those from HV samples. CD38<sup>+</sup> NK cells from NDMM or HV had similar inhibitory effect on MM cell proliferation. Furthermore, CD38<sup>+</sup> NK cells from NDMM fostered CD4<sup>+</sup> T cell differentiation to Tregs more than those from HV.</div></div><div><h3>Conclusion</h3><div>In MM, the proportion and function of CD38<sup>+</sup> NK cells undergo changes, which may be related to the formation of the immunosuppressive microenvironment.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 5","pages":"Article 153107"},"PeriodicalIF":2.3,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144865011","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 : 2025-08-08DOI: 10.1016/j.imbio.2025.153106
Huirong Huang , Wei Xu , Sidong Xiong
Cecal appendix is a unique niche for commensal bacteria, and has been considered the primary site for immunoglobulin A production. Yet its immune function in anti-infection immunity has not been fully understood. In order to elucidate whether cecal patch (CeP), the murine version of appendix, would influence the immune response induced by Mycobacterium tuberculosis (M. tb) and the vaccine effect of Bacillus Calmette-Guérin (BCG), BALB/c mice at 4 weeks of age received appendectomy or sham operation and recovered for 2 weeks before intranasal infection with 2 × 107 CFU Mycobacterium tuberculosis H37Ra. Appendectomy of mice led to a reduction in lung macrophage numbers 7 days post infection (p. i.), and aggravated lung immunohistopathology 4 weeks p. i.. Appendectomized mice vaccinated with 5 × 106 CFU BCG exhibited attenuated BCG-specific serum IgG, reduced lung/splenic IFN-γ+ T response, and weakened T proliferation and cytotoxicity, and eventually worsened lung pathology compared to sham operated mice. Mechanistically, we found that appendectomized mice at a young age (4 weeks) had an attenuated maturation of mesenteric lymph node (MLN) conventional dendritic cells (cDCs), which accounted for the impaired systemic IFN-γ+ T response and cytotoxicity against M. tb. Our data suggest that intact appendix maintain intestinal DC maturation and systemic Th1 induction against M. tb and has an assistant role in increasing immune efficiency of BCG vaccine.
{"title":"Prior appendectomy attenuates the immune protective efficacy of BCG vaccination against Mycobacterium tuberculosis infection","authors":"Huirong Huang , Wei Xu , Sidong Xiong","doi":"10.1016/j.imbio.2025.153106","DOIUrl":"10.1016/j.imbio.2025.153106","url":null,"abstract":"<div><div>Cecal appendix is a unique niche for commensal bacteria, and has been considered the primary site for immunoglobulin A production. Yet its immune function in anti-infection immunity has not been fully understood. In order to elucidate whether cecal patch (CeP), the murine version of appendix, would influence the immune response induced by <em>Mycobacterium tuberculosis</em> (<em>M. tb</em>) and the vaccine effect of Bacillus Calmette-Guérin (BCG), BALB/c mice at 4 weeks of age received appendectomy or sham operation and recovered for 2 weeks before intranasal infection with 2 × 10<sup>7</sup> CFU <em>Mycobacterium tuberculosis</em> H37Ra. Appendectomy of mice led to a reduction in lung macrophage numbers 7 days post infection (p. i.), and aggravated lung immunohistopathology 4 weeks p. i.. Appendectomized mice vaccinated with 5 × 10<sup>6</sup> CFU BCG exhibited attenuated BCG-specific serum IgG, reduced lung/splenic IFN-γ<sup>+</sup> T response, and weakened T proliferation and cytotoxicity, and eventually worsened lung pathology compared to sham operated mice. Mechanistically, we found that appendectomized mice at a young age (4 weeks) had an attenuated maturation of mesenteric lymph node (MLN) conventional dendritic cells (cDCs), which accounted for the impaired systemic IFN-γ<sup>+</sup> T response and cytotoxicity against <em>M. tb</em>. Our data suggest that intact appendix maintain intestinal DC maturation and systemic Th1 induction against <em>M. tb</em> and has an assistant role in increasing immune efficiency of BCG vaccine.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 5","pages":"Article 153106"},"PeriodicalIF":2.3,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144852223","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 elimination of rubella in Iran, achieved in 2019, represents a significant public health success. A limited number of studies have investigated rubella IgG seropositivity levels in Iran across different populations over the last two decades. This study evaluated rubella vaccination coverage and immunity status among Iranian children born between 2016 and 2021, before and during the COVID-19 pandemic.
Methods
Using ELISA, 722 serum samples from children negative for measles and rubella IgM antibodies were analyzed for rubella-specific IgG. Samples were divided into two groups: Group A (born 2016–2018, pre-pandemic) and Group B (born 2019–2021, during the pandemic). Vaccination status was obtained from parental reports.
Results
Overall rubella IgG seropositivity was 75.3 %, with Group B showing significantly higher immunity (82.4 %) than Group A (68.6 %) (p < 0.001). Parental reports indicated MMR vaccination coverage of 95.7 % overall, with Group B coverage (98.9 %) significantly exceeding Group A (92.7 %) (p < 0.001). No significant gender differences were observed. Regional vaccination coverage varied, but rubella IgG positivity was consistent across provinces.
Conclusions
Despite maintaining high MMR vaccination coverage, the overall rubella immunity level in Iranian children in this pilot study remained below the WHO's recommended herd immunity threshold, posing a potential risk for rubella re-emergence. This finding underscored the ongoing surveillance and targeted immunization efforts to sustain rubella elimination in Iran.
{"title":"Serological assessment of rubella immunity in Iranian children post 2019 elimination: A pilot study","authors":"Tasnim Jamalvandi , Akram Sadat Ahmadi , Somayeh Shatizadeh Malekshahi , Maryam Tatari , Azadeh Shadab , Vahid Salimi , Nazanin-Zahra Shafiei-Jandaghi , Talat Mokhtari-Azad","doi":"10.1016/j.imbio.2025.153105","DOIUrl":"10.1016/j.imbio.2025.153105","url":null,"abstract":"<div><h3>Background and aim</h3><div>The elimination of rubella in Iran, achieved in 2019, represents a significant public health success. A limited number of studies have investigated rubella IgG seropositivity levels in Iran across different populations over the last two decades. This study evaluated rubella vaccination coverage and immunity status among Iranian children born between 2016 and 2021, before and during the COVID-19 pandemic.</div></div><div><h3>Methods</h3><div>Using ELISA, 722 serum samples from children negative for measles and rubella IgM antibodies were analyzed for rubella-specific IgG. Samples were divided into two groups: Group A (born 2016–2018, pre-pandemic) and Group B (born 2019–2021, during the pandemic). Vaccination status was obtained from parental reports.</div></div><div><h3>Results</h3><div>Overall rubella IgG seropositivity was 75.3 %, with Group B showing significantly higher immunity (82.4 %) than Group A (68.6 %) (<em>p</em> < 0.001). Parental reports indicated MMR vaccination coverage of 95.7 % overall, with Group B coverage (98.9 %) significantly exceeding Group A (92.7 %) (p < 0.001). No significant gender differences were observed. Regional vaccination coverage varied, but rubella IgG positivity was consistent across provinces.</div></div><div><h3>Conclusions</h3><div>Despite maintaining high MMR vaccination coverage, the overall rubella immunity level in Iranian children in this pilot study remained below the WHO's recommended herd immunity threshold, posing a potential risk for rubella re-emergence. This finding underscored the ongoing surveillance and targeted immunization efforts to sustain rubella elimination in Iran.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 5","pages":"Article 153105"},"PeriodicalIF":2.3,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144827635","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 : 2025-07-01DOI: 10.1016/j.imbio.2025.153102
Yunyun Du , Zhenfeng Fan , Lijiao Li , Yong Xue , Shixiang Zhao
Background
The treatment and prognosis for TP53-mutant acute leukemia (AL) are notably unfavorable. Tumor-derived exosomes are participating in tumorigenesis and immunomodulation. Our objective was to characterize the exosome-mediated immune landscape in TP53-mutant AL.
Methods
Four TP53 AL cell lines were selected for study. RT-qPCR and western blot were used to determine the PD-L1 and TP53. AL exosomes (AL-exos) were co-cultured with PBMC. Flow cytometry was used to determine immune cell and PD-1 expression. Transmission electron microscopy and western blot determination of MOLM-13 and Kasumi-1 exosome surface markers HSP70, CD9, CD63, and CD81. Subsequently, miRNA sequencing was performed.
Results
In TP53 AL cell lines, PD-L1 protein, and mRNA expression increased sequentially in MOLM-13, Kasumi-1, Molt-4, and KG-1 cells. Notably, MOLM-13 and Kasumi-1 exhibited the highest TP53 expression. Flow cytometry results indicated that Kasumi-1-exosomes had a more pronounced effect on immune cells, resulting in a significant reduction in CD8+ T cell populations and a notable increase in Tregs. Notably, its PD-1 expression was significantly elevated. miRNA analysis showed that the DEGs were primarily enriched in signaling transduction and endocytosis pathways.
Conclusion
Kasumi-1-exos promote DNA damage and PD-L1 enrichment through clathrin-mediated plasma membrane fusion, which ultimately leads to AL immune escape characterized primarily by decreased CD8+ T cell expression and increased Treg expression.
{"title":"Kasumi-1 exosome plays a major T-cell immune evasion role in TP53-type acute leukemia","authors":"Yunyun Du , Zhenfeng Fan , Lijiao Li , Yong Xue , Shixiang Zhao","doi":"10.1016/j.imbio.2025.153102","DOIUrl":"10.1016/j.imbio.2025.153102","url":null,"abstract":"<div><h3>Background</h3><div>The treatment and prognosis for TP53-mutant acute leukemia (AL) are notably unfavorable. Tumor-derived exosomes are participating in tumorigenesis and immunomodulation. Our objective was to characterize the exosome-mediated immune landscape in TP53-mutant AL.</div></div><div><h3>Methods</h3><div>Four TP53 AL cell lines were selected for study. RT-qPCR and western blot were used to determine the PD-L1 and TP53. AL exosomes (AL-exos) were co-cultured with PBMC. Flow cytometry was used to determine immune cell and PD-1 expression. Transmission electron microscopy and western blot determination of MOLM-13 and Kasumi-1 exosome surface markers HSP70, CD9, CD63, and CD81. Subsequently, miRNA sequencing was performed.</div></div><div><h3>Results</h3><div>In TP53 AL cell lines, PD-L1 protein, and mRNA expression increased sequentially in MOLM-13, Kasumi-1, Molt-4, and KG-1 cells. Notably, MOLM-13 and Kasumi-1 exhibited the highest TP53 expression. Flow cytometry results indicated that Kasumi-1-exosomes had a more pronounced effect on immune cells, resulting in a significant reduction in CD8<sup>+</sup> T cell populations and a notable increase in Tregs. Notably, its PD-1 expression was significantly elevated. miRNA analysis showed that the DEGs were primarily enriched in signaling transduction and endocytosis pathways.</div></div><div><h3>Conclusion</h3><div>Kasumi-1-exos promote DNA damage and PD-L1 enrichment through clathrin-mediated plasma membrane fusion, which ultimately leads to AL immune escape characterized primarily by decreased CD8<sup>+</sup> T cell expression and increased Treg expression.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 4","pages":"Article 153102"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144656501","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 : 2025-07-01DOI: 10.1016/j.imbio.2025.153100
Jenny N. Fung , Ruben Pio
The complement system is a critical component of the immune system, playing a significant role in pathogen defense and immune regulation. In cancer, it has a complex and dual role, either aiding in immune surveillance or contributing to tumor progression and immune evasion, depending on the specific context. While genetic and epigenetic regulation of complement-related genes has been studied in various diseases, its influence on cancer remains underexplored. This review focuses on how genetic variants in complement pathway genes may modulate cancer susceptibility, progression, and treatment outcomes. Genome-wide association studies (GWAS) have identified several key single nucleotide polymorphisms (SNPs) linked to complement genes, such as C3, C7, CFHR4 and ITGB2, which could influence immune responses and cancer development. Additionally, epigenetic modifications, such as DNA methylation, have been shown to regulate the expression of complement genes in cancer, adding further complexity to our understanding of their role in tumor immunity. Challenges remain in translating genetic and epigenetic insights into therapeutic strategies. The complex nature of cancer, tissue-specific complement regulation, and the difficulty in identifying reliable biomarkers complicate the development of targeted complement-based therapies for precision medicine. Therefore, future research combining genetic, genomic, and epigenomic data, along with functional genomics and proteomics, is needed to elucidate the potential roles of regulatory variants of complement genes in cancer. In addition to mechanistic studies, this information can be used to guide personalized treatment strategies for cancer patients.
{"title":"Genetic variants in complement-related genes: potential implications for cancer risk and progression","authors":"Jenny N. Fung , Ruben Pio","doi":"10.1016/j.imbio.2025.153100","DOIUrl":"10.1016/j.imbio.2025.153100","url":null,"abstract":"<div><div>The complement system is a critical component of the immune system, playing a significant role in pathogen defense and immune regulation. In cancer, it has a complex and dual role, either aiding in immune surveillance or contributing to tumor progression and immune evasion, depending on the specific context. While genetic and epigenetic regulation of complement-related genes has been studied in various diseases, its influence on cancer remains underexplored. This review focuses on how genetic variants in complement pathway genes may modulate cancer susceptibility, progression, and treatment outcomes. Genome-wide association studies (GWAS) have identified several key single nucleotide polymorphisms (SNPs) linked to complement genes, such as <em>C3, C7, CFHR4</em> and <em>ITGB2</em>, which could influence immune responses and cancer development. Additionally, epigenetic modifications, such as DNA methylation, have been shown to regulate the expression of complement genes in cancer, adding further complexity to our understanding of their role in tumor immunity. Challenges remain in translating genetic and epigenetic insights into therapeutic strategies. The complex nature of cancer, tissue-specific complement regulation, and the difficulty in identifying reliable biomarkers complicate the development of targeted complement-based therapies for precision medicine. Therefore, future research combining genetic, genomic, and epigenomic data, along with functional genomics and proteomics, is needed to elucidate the potential roles of regulatory variants of complement genes in cancer. In addition to mechanistic studies, this information can be used to guide personalized treatment strategies for cancer patients.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 4","pages":"Article 153100"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144662457","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 : 2025-07-01DOI: 10.1016/j.imbio.2025.153101
Ying Li , Wei Jia , Jiayang Huang , Jian Liu
Background
Studies have shown that serum microRNA detection holds significant potential in improving the diagnostic accuracy of mycoplasma pneumoniae pneumonia (MPP).
Aims
To investigate the expression and clinical value of miR-98-5p in children with Mycoplasma pneumoniae (MP) infection complicated with diarrhea.
Methods
A total of 122 children diagnosed with MPP were selected as study subjects, and 80 healthy children were selected as controls. Real-time quantitative PCR (RT-qPCR) was used to detect the expression of miR-98-5p. Receiver operating characteristic (ROC) curve was used to determine the diagnostic value of miR-98-5p. The risk factors for MPP with diarrhea were analyzed by means of a logistic regression model. THP-1 cell models with miR-98-5p overexpression and knockdown were established to investigate the potential mechanisms of miR-98-5p in MP infection.
Results
Serum miR-98-5p expression is decreased among children having MPP, and it has a negative correlation with the logMP-DNA level. The miR-98-5p level in children with MPP accompanied by diarrhea is lower compared to that in children with MPP alone. miR-98-5p demonstrates promising diagnostic potential for MPP complicated with diarrhea, and serves as a risk factor for diarrhea in MP-infected children. TargetScan database prediction showed that potential target genes of miR-98-5p, including Synaptotagmin 1 (SYT1) and Tribbles pseudokinase 1(TRIB1), are both associated with digestive system injury induced by MP infection.
Conclusions
The expression of serum miR-98-5p is decreased in children with MPP complicated by diarrhea, and it may become a diagnostic biomarker.
{"title":"Clinical significance of serum miR-98-5p in children with Mycoplasma pneumoniae infection complicated with digestive system damage","authors":"Ying Li , Wei Jia , Jiayang Huang , Jian Liu","doi":"10.1016/j.imbio.2025.153101","DOIUrl":"10.1016/j.imbio.2025.153101","url":null,"abstract":"<div><h3>Background</h3><div>Studies have shown that serum microRNA detection holds significant potential in improving the diagnostic accuracy of <em>mycoplasma pneumoniae</em> pneumonia (MPP).</div></div><div><h3>Aims</h3><div>To investigate the expression and clinical value of miR-98-5p in children with <em>Mycoplasma pneumoniae</em> (MP) infection complicated with diarrhea.</div></div><div><h3>Methods</h3><div>A total of 122 children diagnosed with MPP were selected as study subjects, and 80 healthy children were selected as controls. Real-time quantitative PCR (RT-qPCR) was used to detect the expression of miR-98-5p. Receiver operating characteristic (ROC) curve was used to determine the diagnostic value of miR-98-5p. The risk factors for MPP with diarrhea were analyzed by means of a logistic regression model. THP-1 cell models with miR-98-5p overexpression and knockdown were established to investigate the potential mechanisms of miR-98-5p in MP infection.</div></div><div><h3>Results</h3><div>Serum miR-98-5p expression is decreased among children having MPP, and it has a negative correlation with the logMP-DNA level. The miR-98-5p level in children with MPP accompanied by diarrhea is lower compared to that in children with MPP alone. miR-98-5p demonstrates promising diagnostic potential for MPP complicated with diarrhea, and serves as a risk factor for diarrhea in MP-infected children. TargetScan database prediction showed that potential target genes of miR-98-5p, including Synaptotagmin 1 (SYT1) and Tribbles pseudokinase 1(TRIB1), are both associated with digestive system injury induced by MP infection.</div></div><div><h3>Conclusions</h3><div>The expression of serum miR-98-5p is decreased in children with MPP complicated by diarrhea, and it may become a diagnostic biomarker.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 4","pages":"Article 153101"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144702743","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}