Pub Date : 2026-01-01DOI: 10.1016/j.imbio.2026.153157
Jie Gao , Zhe Li , Xinyue Zhang, Wenshu Huang, Zhiyu Tian, Chuyu Xiao, Yuanyang Zhen, Fang Yu , Xuezhao Cao
Cognitive impairment is a global health problem with increasing prevalence and mortality rates. The complement system plays a key role in the underlying pathological mechanisms. To explore potential strategies for ameliorating and preventing cognitive impairment through targeted therapies involving the complement system, it is crucial to understand the relationship between the complement system and neuroinflammation, as well as its role in the development of cognitive dysfunction. In recent years, the mechanisms involving the complement system and its targeted treatments have become a major focus of research. This review provides an overview of the physiological functions of the complement system, its association with to neuroinflammation, the mechanisms by which it contributes to cognitive impairment, and the potential applications of complement inhibitors in the treatment of cognitive dysfunction.
{"title":"Advances in research on the complement system and cognitive impairment","authors":"Jie Gao , Zhe Li , Xinyue Zhang, Wenshu Huang, Zhiyu Tian, Chuyu Xiao, Yuanyang Zhen, Fang Yu , Xuezhao Cao","doi":"10.1016/j.imbio.2026.153157","DOIUrl":"10.1016/j.imbio.2026.153157","url":null,"abstract":"<div><div>Cognitive impairment is a global health problem with increasing prevalence and mortality rates. The complement system plays a key role in the underlying pathological mechanisms. To explore potential strategies for ameliorating and preventing cognitive impairment through targeted therapies involving the complement system, it is crucial to understand the relationship between the complement system and neuroinflammation, as well as its role in the development of cognitive dysfunction. In recent years, the mechanisms involving the complement system and its targeted treatments have become a major focus of research. This review provides an overview of the physiological functions of the complement system, its association with to neuroinflammation, the mechanisms by which it contributes to cognitive impairment, and the potential applications of complement inhibitors in the treatment of cognitive dysfunction.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 1","pages":"Article 153157"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973287","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 : 2026-01-01DOI: 10.1016/j.imbio.2025.153152
Haijiao Zou , Dongmei Zhou , Shaodan Fang , Han Lin , Hanzhen Xiong , Qingping Jiang , Mingxing Liu , Xiujie Sheng , Miaoxian Ou
Thin endometrium (TE), affecting 1.5 %–9.1 % of reproductive-aged women, emerges as a disturbed decidua microenvironment underpinning implantation failure and recurrent pregnancy loss. Through integrated single-cell transcriptomics with histopathology and multiplex immunofluorescence (TSA) validation, we delineated TE as a disease of coordinated repairment impairment and pro-fibrotic remodeling across stromal and immune compartments. Key findings revealed a pathological imbalance in stromal subsets, including the decrease of regenerative IGFBP3 + Stromal_1 cells and expansion of fibrogenic Stromal_2 populations, driving collagen-dominant extracellular matrix remodeling. Concurrently, immune dysfunction was unmasked. NK cells decreased and shifted from immune surveillance to a pro-inflammatory phenotype, T cells transitioned from immune regulation to extracellular matrix remodeling effectors and macrophages adopted a pro-fibrotic phenotype with lipid metabolic collapse. CellChat analysis pinpointed suppression of GZMA-PARD3 and APOE-TREM2 axes as drivers of stromal dysfunction, while the hyperactivated adhesion (LAMA3) and collagen pathways served as central mediators of the fibro-inflammatory cascade. These findings, based on single-cell RNA-seq and spatial verification, suggest therapeutic targets for restoring endometrial homeostasis in TE. These findings suggested that TE as a disease of progressive stromal-immune fibrosis dysregulation, offering novel therapeutic targets to restore endometrial repairment and microenvironmental homeostasis.
{"title":"Single-cell transcriptome reveals that immune cells inhibit the repairment of IGFBP3 + stromal cells in thin endometrium","authors":"Haijiao Zou , Dongmei Zhou , Shaodan Fang , Han Lin , Hanzhen Xiong , Qingping Jiang , Mingxing Liu , Xiujie Sheng , Miaoxian Ou","doi":"10.1016/j.imbio.2025.153152","DOIUrl":"10.1016/j.imbio.2025.153152","url":null,"abstract":"<div><div>Thin endometrium (TE), affecting 1.5 %–9.1 % of reproductive-aged women, emerges as a disturbed decidua microenvironment underpinning implantation failure and recurrent pregnancy loss. Through integrated single-cell transcriptomics with histopathology and multiplex immunofluorescence (TSA) validation, we delineated TE as a disease of coordinated repairment impairment and pro-fibrotic remodeling across stromal and immune compartments. Key findings revealed a pathological imbalance in stromal subsets, including the decrease of regenerative IGFBP3 + Stromal_1 cells and expansion of fibrogenic Stromal_2 populations, driving collagen-dominant extracellular matrix remodeling. Concurrently, immune dysfunction was unmasked. NK cells decreased and shifted from immune surveillance to a pro-inflammatory phenotype, T cells transitioned from immune regulation to extracellular matrix remodeling effectors and macrophages adopted a pro-fibrotic phenotype with lipid metabolic collapse. CellChat analysis pinpointed suppression of GZMA-PARD3 and APOE-TREM2 axes as drivers of stromal dysfunction, while the hyperactivated adhesion (LAMA3) and collagen pathways served as central mediators of the fibro-inflammatory cascade. These findings, based on single-cell RNA-seq and spatial verification, suggest therapeutic targets for restoring endometrial homeostasis in TE. These findings suggested that TE as a disease of progressive stromal-immune fibrosis dysregulation, offering novel therapeutic targets to restore endometrial repairment and microenvironmental homeostasis.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 1","pages":"Article 153152"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911098","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 : 2026-01-01DOI: 10.1016/j.imbio.2025.153150
Qing Wei , Min Wu , Yuxiang Gong , Minyu Yang , Haifeng Ni , Pingsheng Chen , Dong Wei , Xuan Shi , Bin Wang , Bicheng Liu
Background
Renal interstitial inflammation (RII) is a common pathological feature in immunoglobulin A nephropathy (IgAN) and may predict renal outcomes, but further validation is required. This study evaluated the prognostic value of RII and inflammatory cell infiltration in patients with IgAN.
Methods
This retrospective cohort study included adults with biopsy-confirmed IgAN. Renal interstitial inflammation was categorised as 0 (absent), 1 (around atrophic tubules) or 2 (beyond atrophic tubules). Interstitial CD3+, CD20+ and CD68+ cells were quantified via immunohistochemistry. The primary outcome was a composite of a ≥ 40 % decline in the estimated glomerular filtration rate or end-stage renal disease.
Results
Of the 112 participating patients, 30 (26.8 %) experienced the primary outcome. A higher RII score was associated with increased risk of progression (hazard ratio for score 2 vs 0: 4.73, 95 % confidence interval [CI]: 2.01–11.13, p = 0.001). Patients with the outcome had higher densities of interstitial CD3+, CD20+ and CD68+ cells at biopsy. Kaplan–Meier analysis showed lower renal survival in patients with higher inflammatory cell densities (p < 0.05). The RII score alone had an area under the curve of 0.804 (95 % CI: 0.715–0.894) for predicting progression, which improved to 0.865 (95 % CI: 0.779–0.951) when combined with the Oxford classification score.
Conclusion
The severity of RII is independently associated with renal prognosis in IgAN. Immunohistochemical evaluation of inflammatory cell infiltration may improve risk stratification and guide early intervention.
背景：肾间质炎症（RII）是免疫球蛋白a肾病（IgAN）的常见病理特征，可以预测肾脏预后，但需要进一步验证。本研究评估了RII和炎症细胞浸润在IgAN患者中的预后价值。方法：这项回顾性队列研究纳入了活检证实的IgAN成人。肾间质炎症分为0（无）、1（萎缩小管周围）和2（萎缩小管外）。免疫组织化学定量检测间质CD3+、CD20+和CD68+细胞。主要终点是肾小球滤过率估计下降≥40%或终末期肾病的综合指标。结果：在112例参与研究的患者中，30例（26.8%）经历了主要结局。较高的RII评分与进展风险增加相关（评分2 vs 0的风险比：4.73,95%可信区间[CI]: 2.01-11.13, p = 0.001）。结果患者活检时间质CD3+、CD20+和CD68+细胞密度较高。Kaplan-Meier分析显示，炎症细胞密度较高的患者肾脏存活率较低(p)。结论：IgAN患者RII的严重程度与肾脏预后独立相关。免疫组化评价炎症细胞浸润可改善危险分层，指导早期干预。
{"title":"Predictive value of interstitial inflammation for renal outcome in patients with immunoglobulin a nephropathy","authors":"Qing Wei , Min Wu , Yuxiang Gong , Minyu Yang , Haifeng Ni , Pingsheng Chen , Dong Wei , Xuan Shi , Bin Wang , Bicheng Liu","doi":"10.1016/j.imbio.2025.153150","DOIUrl":"10.1016/j.imbio.2025.153150","url":null,"abstract":"<div><h3>Background</h3><div>Renal interstitial inflammation (RII) is a common pathological feature in immunoglobulin A nephropathy (IgAN) and may predict renal outcomes, but further validation is required. This study evaluated the prognostic value of RII and inflammatory cell infiltration in patients with IgAN.</div></div><div><h3>Methods</h3><div>This retrospective cohort study included adults with biopsy-confirmed IgAN. Renal interstitial inflammation was categorised as 0 (absent), 1 (around atrophic tubules) or 2 (beyond atrophic tubules). Interstitial CD3<sup>+</sup>, CD20<sup>+</sup> and CD68<sup>+</sup> cells were quantified via immunohistochemistry. The primary outcome was a composite of a ≥ 40 % decline in the estimated glomerular filtration rate or end-stage renal disease.</div></div><div><h3>Results</h3><div>Of the 112 participating patients, 30 (26.8 %) experienced the primary outcome. A higher RII score was associated with increased risk of progression (hazard ratio for score 2 vs 0: 4.73, 95 % confidence interval [CI]: 2.01–11.13, <em>p</em> = 0.001). Patients with the outcome had higher densities of interstitial CD3<sup>+</sup>, CD20<sup>+</sup> and CD68<sup>+</sup> cells at biopsy. Kaplan–Meier analysis showed lower renal survival in patients with higher inflammatory cell densities (<em>p</em> < 0.05). The RII score alone had an area under the curve of 0.804 (95 % CI: 0.715–0.894) for predicting progression, which improved to 0.865 (95 % CI: 0.779–0.951) when combined with the Oxford classification score.</div></div><div><h3>Conclusion</h3><div>The severity of RII is independently associated with renal prognosis in IgAN. Immunohistochemical evaluation of inflammatory cell infiltration may improve risk stratification and guide early intervention.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 1","pages":"Article 153150"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911111","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 : 2026-01-01DOI: 10.1016/j.imbio.2026.153156
Junsheng Hou , Min Li
In immunocompromised individuals, infections due to Candida albicans (C. albicans) can be life-threatening. Recognition of the insoluble β-glucan derived from the C. albicans cell wall (CaIG) by Dectin-1 in macrophages initiates an inflammatory reaction that is critical for clearing the fungal infection. However, uncontrolled inflammation may lead to septic shock. Research has established that miR-210 is strongly upregulated in THP-1-derived macrophages (THP-1 macrophages) following CaIG stimulation. MiR-210 has been implicated in the metabolic and immunological responses of macrophages in various infectious and inflammatory disease models. Nevertheless, whether miR-210 modulates Dectin-1-activated inflammation remains unclear. An in vitro inflammation model was established using CaIG-stimulated THP-1 macrophages in the current research. By using miR-210 mimic and inhibitor transfection approaches, we observed that miR-210 overexpression significantly reduced CaIG-induced IL-6 and TNF-α expression, whereas inhibition of endogenous miR-210 enhanced their production. Furthermore, by inhibiting CaIG-triggered spleen tyrosine kinase (Syk) activation and subsequent IκBα phosphorylation, miR-210 effectively prevents the accumulation of NF-κB p65 in the nucleus in THP-1 macrophages. These findings demonstrate that miR-210 participates in negative feedback to limit CaIG-triggered inflammation, primarily through downregulating the Syk-NF-κB signaling cascade. In summary, our findings reveal that miR-210 acts as a precise inflammatory modulator in macrophages, highlighting its therapeutic potential.
{"title":"MiR-210 suppresses Candida albicans-derived β-glucan-induced inflammation in THP-1-derived macrophages via the Syk-NF-κB pathway","authors":"Junsheng Hou , Min Li","doi":"10.1016/j.imbio.2026.153156","DOIUrl":"10.1016/j.imbio.2026.153156","url":null,"abstract":"<div><div>In immunocompromised individuals, infections due to <em>Candida albicans (C. albicans)</em> can be life-threatening. Recognition of the insoluble β-glucan derived from the <em>C. albicans</em> cell wall <em>(CaIG)</em> by Dectin-1 in macrophages initiates an inflammatory reaction that is critical for clearing the fungal infection. However, uncontrolled inflammation may lead to septic shock. Research has established that miR-210 is strongly upregulated in THP-1-derived macrophages (THP-1 macrophages) following <em>CaIG</em> stimulation. MiR-210 has been implicated in the metabolic and immunological responses of macrophages in various infectious and inflammatory disease models. Nevertheless, whether miR-210 modulates Dectin-1-activated inflammation remains unclear. An in vitro inflammation model was established using <em>CaIG</em>-stimulated THP-1 macrophages in the current research. By using miR-210 mimic and inhibitor transfection approaches, we observed that miR-210 overexpression significantly reduced <em>CaIG</em>-induced IL-6 and TNF-α expression, whereas inhibition of endogenous miR-210 enhanced their production. Furthermore, by inhibiting <em>CaIG</em>-triggered spleen tyrosine kinase (Syk) activation and subsequent IκBα phosphorylation, miR-210 effectively prevents the accumulation of NF-κB p65 in the nucleus in THP-1 macrophages. These findings demonstrate that miR-210 participates in negative feedback to limit <em>CaIG</em>-triggered inflammation, primarily through downregulating the Syk-NF-κB signaling cascade. In summary, our findings reveal that miR-210 acts as a precise inflammatory modulator in macrophages, highlighting its therapeutic potential.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 1","pages":"Article 153156"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973288","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 : 2026-01-01DOI: 10.1016/j.imbio.2025.153151
Borros Arneth
Background
Immunometabolism explores how immune-cell function depends on cellular energy metabolism. Recent insights demonstrate that nutrient utilization dictates activation, polarization, and tolerance.
Aims
To systematically review human studies on T-cell and macrophage metabolism, identify converging pathways, and outline translational implications for inflammation, autoimmunity, and cancer.
Methods
Following PRISMA 2020 guidelines, PubMed was searched (2015–2025) using predefined MeSH terms (“immunometabolism”, “T lymphocytes”, “macrophages”, “metabolic reprogramming”). Of 999 records, 67 met inclusion criteria (human data, peer-reviewed, quantitative endpoints). Bias was assessed with ROBIS.
Results
Effector T cells and M1 macrophages favor glycolysis for rapid ATP and pro-inflammatory signaling, whereas memory T cells and M2 macrophages rely on oxidative phosphorylation and fatty-acid oxidation for sustained energy and tolerance. mTORC1/AMPK signaling, glutaminolysis, and the kynurenine pathway integrate metabolic and immune cues. Metabolic dysregulation in obesity or tumor microenvironments skews these pathways, driving chronic inflammation or immune escape.
Conclusions
Human immunometabolism is defined by dynamic substrate switching. Targeting glycolysis, FAO, or tryptophan metabolism offers therapeutic leverage in cancer and autoimmune disease. Future directions include single-cell and spatial metabolomics and integrative metabolic-immune modeling.
{"title":"Immunometabolism of T cells and macrophages: Human translational perspectives","authors":"Borros Arneth","doi":"10.1016/j.imbio.2025.153151","DOIUrl":"10.1016/j.imbio.2025.153151","url":null,"abstract":"<div><h3>Background</h3><div>Immunometabolism explores how immune-cell function depends on cellular energy metabolism. Recent insights demonstrate that nutrient utilization dictates activation, polarization, and tolerance.</div></div><div><h3>Aims</h3><div>To systematically review human studies on T-cell and macrophage metabolism, identify converging pathways, and outline translational implications for inflammation, autoimmunity, and cancer.</div></div><div><h3>Methods</h3><div>Following PRISMA 2020 guidelines, PubMed was searched (2015–2025) using predefined MeSH terms (“immunometabolism”, “T lymphocytes”, “macrophages”, “metabolic reprogramming”). Of 999 records, 67 met inclusion criteria (human data, peer-reviewed, quantitative endpoints). Bias was assessed with ROBIS.</div></div><div><h3>Results</h3><div>Effector T cells and M1 macrophages favor glycolysis for rapid ATP and pro-inflammatory signaling, whereas memory T cells and M2 macrophages rely on oxidative phosphorylation and fatty-acid oxidation for sustained energy and tolerance. mTORC1/AMPK signaling, glutaminolysis, and the kynurenine pathway integrate metabolic and immune cues. Metabolic dysregulation in obesity or tumor microenvironments skews these pathways, driving chronic inflammation or immune escape.</div></div><div><h3>Conclusions</h3><div>Human immunometabolism is defined by dynamic substrate switching. Targeting glycolysis, FAO, or tryptophan metabolism offers therapeutic leverage in cancer and autoimmune disease. Future directions include single-cell and spatial metabolomics and integrative metabolic-immune modeling.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 1","pages":"Article 153151"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911149","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 : 2026-01-01DOI: 10.1016/j.imbio.2025.153154
Hong Li , Xiaoliang Du , Yongze Liu, Jiawu Yang, Qinglang Dai, Yuan Liao, Feng Li
Background
Acute lung injury (ALI) is an acute lung inflammatory disease that is difficult to cure and has a poor prognosis. Macrophages play a key role in the pathogenesis of ALI, and their different phenotypes and functions affect the progression of the disease. This study aimed to explore how ZBP1 affects the progression of ALI via the regulation of macrophage inflammatory phenotype.
Methods
A RAW264.7 cell injury model and an ALI mouse model were established via LPS induction for experimental investigation. The degree of lung injury was determined by HE staining, the protein concentration in the bronchoalveolar lavage fluid (BALF), the wet/dry weight ratio of the lung tissue, and lung myeloperoxidase (MPO) activity. The levels of related proteins, genes and inflammatory factors were detected via Western blotting, RT–qPCR and ELISA. Bioinformatics prediction and dual-luciferase reporter gene assays were used to demonstrate the interaction between miR-1298-5p and ZBP1.
Results
ZBP1 was highly expressed in ALI and its expression was associated with the degree of M1 macrophage polarization. ZBP1 knockdown significantly attenuated LPS-induced pathological damage to lung tissue and reduced the lung wet/dry weight ratio, protein content in BALF, MPO activity and levels of the proinflammatory cytokines IL-1β, IL-6, and TNF-α in lung tissue. Further studies revealed that ZBP1 knockdown inhibited the activation of the NF-κB signaling pathway, thereby reducing ROS levels while increasing the mitochondrial membrane potential, ATP content and expression of the mitochondrial protein TOM20, ultimately ameliorating mitochondrial dysfunction. Mechanistically, miR-1298-5p is expressed at low levels in ALI and negatively regulates ZBP1 expression. In addition, the NF-κB activator PMA reversed the inhibitory effect of ZBP1 knockdown on M1 macrophage polarization.
Conclusion
miR-1298-5p downregulates ZBP1 expression and inhibits NF-κB signaling pathway-mediated mitochondrial dysfunction, thereby inhibiting the M1 polarization of macrophages and the progression of ALI.
{"title":"ZBP1 aggravates acute lung injury in mice by promoting the macrophage inflammatory phenotype","authors":"Hong Li , Xiaoliang Du , Yongze Liu, Jiawu Yang, Qinglang Dai, Yuan Liao, Feng Li","doi":"10.1016/j.imbio.2025.153154","DOIUrl":"10.1016/j.imbio.2025.153154","url":null,"abstract":"<div><h3>Background</h3><div>Acute lung injury (ALI) is an acute lung inflammatory disease that is difficult to cure and has a poor prognosis. Macrophages play a key role in the pathogenesis of ALI, and their different phenotypes and functions affect the progression of the disease. This study aimed to explore how ZBP1 affects the progression of ALI via the regulation of macrophage inflammatory phenotype.</div></div><div><h3>Methods</h3><div>A RAW264.7 cell injury model and an ALI mouse model were established via LPS induction for experimental investigation. The degree of lung injury was determined by HE staining, the protein concentration in the bronchoalveolar lavage fluid (BALF), the wet/dry weight ratio of the lung tissue, and lung myeloperoxidase (MPO) activity. The levels of related proteins, genes and inflammatory factors were detected via Western blotting, RT–qPCR and ELISA. Bioinformatics prediction and dual-luciferase reporter gene assays were used to demonstrate the interaction between miR-1298-5p and ZBP1.</div></div><div><h3>Results</h3><div>ZBP1 was highly expressed in ALI and its expression was associated with the degree of M1 macrophage polarization. ZBP1 knockdown significantly attenuated LPS-induced pathological damage to lung tissue and reduced the lung wet/dry weight ratio, protein content in BALF, MPO activity and levels of the proinflammatory cytokines IL-1β, IL-6, and TNF-α in lung tissue. Further studies revealed that ZBP1 knockdown inhibited the activation of the NF-κB signaling pathway, thereby reducing ROS levels while increasing the mitochondrial membrane potential, ATP content and expression of the mitochondrial protein TOM20, ultimately ameliorating mitochondrial dysfunction. Mechanistically, miR-1298-5p is expressed at low levels in ALI and negatively regulates ZBP1 expression. In addition, the NF-κB activator PMA reversed the inhibitory effect of ZBP1 knockdown on M1 macrophage polarization.</div></div><div><h3>Conclusion</h3><div>miR-1298-5p downregulates ZBP1 expression and inhibits NF-κB signaling pathway-mediated mitochondrial dysfunction, thereby inhibiting the M1 polarization of macrophages and the progression of ALI.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 1","pages":"Article 153154"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911144","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 : 2026-01-01DOI: 10.1016/j.imbio.2026.153155
Juanfeng Lao , Manman Zhu , Liangjian Kuang , Changliang Luo , Zhongyuan Lin , Qiongying Ling , Yulin Yuan , Yongjian Wu , Liuyang Shu
Programmed death-1 (PD-1) immune checkpoint inhibition has transformed the therapeutic landscape of non-small cell lung cancer (NSCLC), while a proportion of NSCLC cases exhibited primary or acquired resistance, reflecting the imperative to elucidate resistance mechanisms and identify synergistic immunomodulatory targets. In this context, strategies that augment the functional competence of effector T cells represent an important direction for improving immunotherapeutic efficacy. This study sought to characterize the immunological role of signaling lymphocytic activation molecule family member 7 (SLAMF7) in modulating T cell–mediated responses in non-small cell lung cancer (NSCLC). Peripheral T cells from NSCLC cases exhibited an escalated SLAMF7 expression level relative to healthy controls. Furthermore, this upregulation was more pronounced in patients who demonstrated clinical responsiveness to anti-PD-1 therapy. Moreover, SLAMF7 expression level demonstrated a positive link with both T cell abundance and the frequencies of cytokine-secreting T cell subsets. Mechanistic insights derived from a murine lung carcinoma model confirmed these outcomes. SLAMF7-deficient mice exhibited impaired anti-tumor immunity, as evidenced by accelerated tumor progression and attenuated effector cytokines production. Conversely, therapeutic co-engagement of SLAMF7 via recombinant SLAMF7 (rm-SLAMF7) plus PD-1 blockade significantly amplified anti-tumor responses, characterized by enhanced T cell expansion, activation, and cytotoxic potential. Consequently, these outcomes suggested that targeting SLAMF7 may offer a strategy to enhance PD-1-directed immunotherapy in NSCLC.
{"title":"SLAMF7 improves the efficacy of PD-1 immunotherapy by enhancing T cell response in non-small cell lung cancer","authors":"Juanfeng Lao , Manman Zhu , Liangjian Kuang , Changliang Luo , Zhongyuan Lin , Qiongying Ling , Yulin Yuan , Yongjian Wu , Liuyang Shu","doi":"10.1016/j.imbio.2026.153155","DOIUrl":"10.1016/j.imbio.2026.153155","url":null,"abstract":"<div><div>Programmed death-1 (PD-1) immune checkpoint inhibition has transformed the therapeutic landscape of non-small cell lung cancer (NSCLC), while a proportion of NSCLC cases exhibited primary or acquired resistance, reflecting the imperative to elucidate resistance mechanisms and identify synergistic immunomodulatory targets. In this context, strategies that augment the functional competence of effector T cells represent an important direction for improving immunotherapeutic efficacy. This study sought to characterize the immunological role of signaling lymphocytic activation molecule family member 7 (SLAMF7) in modulating T cell–mediated responses in non-small cell lung cancer (NSCLC). Peripheral T cells from NSCLC cases exhibited an escalated SLAMF7 expression level relative to healthy controls. Furthermore, this upregulation was more pronounced in patients who demonstrated clinical responsiveness to anti-PD-1 therapy. Moreover, SLAMF7 expression level demonstrated a positive link with both T cell abundance and the frequencies of cytokine-secreting T cell subsets. Mechanistic insights derived from a murine lung carcinoma model confirmed these outcomes. SLAMF7-deficient mice exhibited impaired anti-tumor immunity, as evidenced by accelerated tumor progression and attenuated effector cytokines production. Conversely, therapeutic co-engagement of SLAMF7 via recombinant SLAMF7 (rm-SLAMF7) plus PD-1 blockade significantly amplified anti-tumor responses, characterized by enhanced T cell expansion, activation, and cytotoxic potential. Consequently, these outcomes suggested that targeting SLAMF7 may offer a strategy to enhance PD-1-directed immunotherapy in NSCLC.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 1","pages":"Article 153155"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973289","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 : 2025-12-26DOI: 10.1016/j.imbio.2025.153153
Paula X. Losada , Juan Antonio Villatoro-García , Julio Jaramillo , Lina Serrato , Karen Álvarez , Daniel Rodriguez , Juan Camilo Diaz , Ricardo Pineda , Pedro Carmona-Saez , Mauricio Rojas , Gloria Vásquez
Objective
Lupus Nephritis (LN) is a common and serious complication in patients with Systemic Lupus Erythematosus (SLE), an immune complex-mediated disease. Extracellular Vesicles (EVs) can carry autoantigens recognized by circulating antibodies, forming immune complexes (ICs) that may deposit in the kidney and be detected by inflammatory cells like monocytes in LN class III/IV. The SLAN marker identifies a subset of non-classical monocytes considered highly inflammatory and migratory. However, the interactions between these blood components in the context of LN remain incompletely understood. We aimed to analyze the transcriptional profiles of circulating SLAN+/− monocytes from LN patients and assess the influence of patient-derived EVs on SLAN− monocyte gene expression.
Methods
SLAN+/− monocytes were isolated from female LN patients, and controls were matched by similar age. Plasma-derived EVs from LN patients were co-incubated with SLAN-monocytes from controls. Next-generation RNA sequencing was employed to evaluate gene expression profiles and changes induced by EVs, followed by bioinformatic analysis to identify differential gene expression and functional pathways.
Results
Monocytes from LN patients exhibited an inflammatory profile characterized by elevated interferon response genes. The SLAN+ fraction displayed biological processes relevant to renal pathology, including cellular stress response, differentiation, and migration pathways. EVs elicited an inflammatory response with differentiation potential in non-SLAN monocytes.
Conclusions
These findings suggest that EVs transport antigenic molecules and induce transcriptional changes in monocytes toward inflammatory and migratory states, implicating them in LN pathogenesis and highlighting their potential as therapeutic targets.
{"title":"Unraveling SLAN+/− monocytes transcriptomics in lupus and extracellular vesicles effects","authors":"Paula X. Losada , Juan Antonio Villatoro-García , Julio Jaramillo , Lina Serrato , Karen Álvarez , Daniel Rodriguez , Juan Camilo Diaz , Ricardo Pineda , Pedro Carmona-Saez , Mauricio Rojas , Gloria Vásquez","doi":"10.1016/j.imbio.2025.153153","DOIUrl":"10.1016/j.imbio.2025.153153","url":null,"abstract":"<div><h3>Objective</h3><div>Lupus Nephritis (LN) is a common and serious complication in patients with Systemic Lupus Erythematosus (SLE), an immune complex-mediated disease. Extracellular Vesicles (EVs) can carry autoantigens recognized by circulating antibodies, forming immune complexes (ICs) that may deposit in the kidney and be detected by inflammatory cells like monocytes in LN class III/IV. The SLAN marker identifies a subset of non-classical monocytes considered highly inflammatory and migratory. However, the interactions between these blood components in the context of LN remain incompletely understood. We aimed to analyze the transcriptional profiles of circulating SLAN+/− monocytes from LN patients and assess the influence of patient-derived EVs on SLAN− monocyte gene expression.</div></div><div><h3>Methods</h3><div>SLAN+/− monocytes were isolated from female LN patients, and controls were matched by similar age. Plasma-derived EVs from LN patients were co-incubated with SLAN-monocytes from controls. Next-generation RNA sequencing was employed to evaluate gene expression profiles and changes induced by EVs, followed by bioinformatic analysis to identify differential gene expression and functional pathways.</div></div><div><h3>Results</h3><div>Monocytes from LN patients exhibited an inflammatory profile characterized by elevated interferon response genes. The SLAN+ fraction displayed biological processes relevant to renal pathology, including cellular stress response, differentiation, and migration pathways. EVs elicited an inflammatory response with differentiation potential in non-SLAN monocytes.</div></div><div><h3>Conclusions</h3><div>These findings suggest that EVs transport antigenic molecules and induce transcriptional changes in monocytes toward inflammatory and migratory states, implicating them in LN pathogenesis and highlighting their potential as therapeutic targets.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 2","pages":"Article 153153"},"PeriodicalIF":2.3,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976249","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 : 2025-12-19DOI: 10.1016/j.imbio.2025.153149
Barbara E Rolfe, John D Lee, Trent M Woodruff
This Immunobiology special issue commemorates the 30th International Complement Workshop, held for the first time in Australia. Reflecting the global reach of complement research, the Workshop brought together delegates from 24 countries and showcased a diverse range of topics including: Structural insight into complement function; Mechanisms of activation and regulation; Cell-autonomous and intracellular complement; Novel and non-canonical roles; Complement in infection and disease; and Biomarkers, diagnostics and therapeutics. In addition to invited reviews and an original research article, this issue includes all accepted abstracts from the Workshop. Together, these contributions provide a compelling snapshot of a rapidly evolving field, one that continues to expand in scope and deepen mechanistic understanding. They highlight the dynamic, interdisciplinary and collaborative nature of complement research, and set the stage for future discoveries that will translate into clinical benefit.
{"title":"Preface to the special issue for the 30th International Complement Workshop Brisbane 2025.","authors":"Barbara E Rolfe, John D Lee, Trent M Woodruff","doi":"10.1016/j.imbio.2025.153149","DOIUrl":"https://doi.org/10.1016/j.imbio.2025.153149","url":null,"abstract":"<p><p>This Immunobiology special issue commemorates the 30th International Complement Workshop, held for the first time in Australia. Reflecting the global reach of complement research, the Workshop brought together delegates from 24 countries and showcased a diverse range of topics including: Structural insight into complement function; Mechanisms of activation and regulation; Cell-autonomous and intracellular complement; Novel and non-canonical roles; Complement in infection and disease; and Biomarkers, diagnostics and therapeutics. In addition to invited reviews and an original research article, this issue includes all accepted abstracts from the Workshop. Together, these contributions provide a compelling snapshot of a rapidly evolving field, one that continues to expand in scope and deepen mechanistic understanding. They highlight the dynamic, interdisciplinary and collaborative nature of complement research, and set the stage for future discoveries that will translate into clinical benefit.</p>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":" ","pages":"153149"},"PeriodicalIF":2.3,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827669","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 : 2025-12-03DOI: 10.1016/j.imbio.2025.153147
Ke Luo, Tianhuang Liu
<div><h3>Background</h3><div>Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) represents a serious clinical condition characterized by acute deterioration of liver function in patients with chronic liver disease. Prompt and precise prognostic assessment is key to guiding therapy and improving clinical outcomes.</div></div><div><h3>Objective</h3><div>To investigate the clinical value of combined assessment of inflammatory biomarkers and liver reserve function indicators in predicting the 12-week prognosis of patients with HBV-ACLF.</div></div><div><h3>Methods</h3><div>We analyzed clinical data from 150 HBV-ACLF patients admitted between July 2022 and December 2024. Patients were followed for 12 weeks and categorized into survival or death groups. Baseline data included inflammatory biomarkers [Neutrophil count (NEUT), Lymphocyte count (LYM), Monocyte count (MON), Platelet count (PLT), Procalcitonin (PCT)] and liver function indicators [Albumin (ALB), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Total bilirubin (TBIL), International normalized ratio (INR)]. Pearson correlation analysis was performed for statistically significant indicators. The construction of the combined prediction model for 12-week prognosis of HBV-ACLF was performed using multivariate logistic regression analysis. The application value of combining inflammatory biomarkers with liver reserve function indicators in the 12-week prognostic assessment of HBV-ACLF was evaluated using ROC curve analysis. <em>P</em>-value <0.05 was considered statistically significant.</div></div><div><h3>Results</h3><div>Among the 150 patients with HBV-ACLF, 102 survived and 48 died. Compared to the survival group, patients in the death group were significantly older (<em>P</em> = 0.032) and included a lower proportion of males (<em>P</em> = 0.001). Among the laboratory indicators, the death group had significantly elevated NEUT, TBIL, INR, and PCT levels (<em>P</em> < 0.05), while LYM, PLT, and ALB levels were significantly decreased (<em>P</em> < 0.05). Pearson correlation analysis revealed that age (<em>r</em> = 0.175, <em>P</em> = 0.032), NEUT (<em>r</em> = 0.184, <em>P</em> = 0.024), TBIL (<em>r</em> = 0.272, <em>P</em> = 0.001), and PCT (<em>r</em> = 0.161, <em>P</em> = 0.049) were positively correlated with prognosis, while gender (<em>r</em> = −0.272, <em>P</em> = 0.001), LYM (<em>r</em> = −0.188, <em>P</em> = 0.021), PLT (<em>r</em> = −0.189, <em>P</em> = 0.021), and ALB (<em>r</em> = −0.197, <em>P</em> = 0.015) were negatively correlated. ROC curve analysis revealed that the AUCs for predicting the 12-week prognosis using NEUT, LYM, PLT, ALB, TBIL, and PCT alone were 0.615, 0.696, 0.616, 0.620, 0.671, and 0.608, respectively. When combined, the AUC significantly increased to 0.817 (<em>P</em> < 0.001), with a sensitivity of 79.17 % and a specificity of 76.47 %, indicating that combined indicators can more accurately predict the prognosis of
背景：乙型肝炎病毒相关的急性慢性肝衰竭（HBV-ACLF）是一种以慢性肝病患者肝功能急性恶化为特征的严重临床疾病。及时准确的预后评估是指导治疗和改善临床结果的关键。目的探讨炎症生物标志物与肝脏储备功能指标联合评估在预测HBV-ACLF患者12周预后中的临床价值。方法分析2022年7月至2024年12月收治的150例HBV-ACLF患者的临床资料。随访12周，分为生存组和死亡组。基线数据包括炎症生物标志物[中性粒细胞计数（NEUT）、淋巴细胞计数（LYM）、单核细胞计数（MON）、血小板计数（PLT）、降钙素原（PCT）]和肝功能指标[白蛋白（ALB）、丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、总胆红素（TBIL）、国际标准化比值（INR）]。对有统计学意义的指标进行Pearson相关分析。采用多因素logistic回归分析构建HBV-ACLF 12周预后联合预测模型。采用ROC曲线分析评价炎症生物标志物联合肝储备功能指标在HBV-ACLF患者12周预后评估中的应用价值。p值<；0.05认为有统计学意义。结果150例HBV-ACLF患者中，102例存活，48例死亡。与生存组相比，死亡组患者年龄明显增大（P = 0.032），男性比例较低（P = 0.001）。实验室指标中，死亡组NEUT、TBIL、INR、PCT水平显著升高（P < 0.05）， LYM、PLT、ALB水平显著降低（P < 0.05）。Pearson相关分析显示，年龄（r = 0.175, P = 0.032）、NEUT （r = 0.184, P = 0.024）、TBIL （r = 0.272, P = 0.001）、PCT （r = 0.161, P = 0.049）与预后呈正相关，性别（r = - 0.272, P = 0.001）、LYM （r = - 0.188, P = 0.021）、PLT （r = - 0.189, P = 0.021）、ALB （r = - 0.197, P = 0.015）与预后呈负相关。ROC曲线分析显示，单独使用NEUT、LYM、PLT、ALB、TBIL、PCT预测12周预后的auc分别为0.615、0.696、0.616、0.620、0.671、0.608。联合使用时，AUC显著增加至0.817 (P < 0.001)，敏感性为79.17%，特异性为76.47%，说明联合使用指标能更准确地预测HBV-ACLF患者的预后。结论联合评估炎症生物标志物和肝脏储备功能指标可以更全面、准确地评估HBV-ACLF患者的病情严重程度，对预测其12周预后具有重要的临床价值。
{"title":"The clinical value of combined assessment of inflammatory biomarkers and liver reserve function in predicting the 12-week prognosis of HBV-ACLF","authors":"Ke Luo, Tianhuang Liu","doi":"10.1016/j.imbio.2025.153147","DOIUrl":"10.1016/j.imbio.2025.153147","url":null,"abstract":"<div><h3>Background</h3><div>Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) represents a serious clinical condition characterized by acute deterioration of liver function in patients with chronic liver disease. Prompt and precise prognostic assessment is key to guiding therapy and improving clinical outcomes.</div></div><div><h3>Objective</h3><div>To investigate the clinical value of combined assessment of inflammatory biomarkers and liver reserve function indicators in predicting the 12-week prognosis of patients with HBV-ACLF.</div></div><div><h3>Methods</h3><div>We analyzed clinical data from 150 HBV-ACLF patients admitted between July 2022 and December 2024. Patients were followed for 12 weeks and categorized into survival or death groups. Baseline data included inflammatory biomarkers [Neutrophil count (NEUT), Lymphocyte count (LYM), Monocyte count (MON), Platelet count (PLT), Procalcitonin (PCT)] and liver function indicators [Albumin (ALB), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Total bilirubin (TBIL), International normalized ratio (INR)]. Pearson correlation analysis was performed for statistically significant indicators. The construction of the combined prediction model for 12-week prognosis of HBV-ACLF was performed using multivariate logistic regression analysis. The application value of combining inflammatory biomarkers with liver reserve function indicators in the 12-week prognostic assessment of HBV-ACLF was evaluated using ROC curve analysis. <em>P</em>-value <0.05 was considered statistically significant.</div></div><div><h3>Results</h3><div>Among the 150 patients with HBV-ACLF, 102 survived and 48 died. Compared to the survival group, patients in the death group were significantly older (<em>P</em> = 0.032) and included a lower proportion of males (<em>P</em> = 0.001). Among the laboratory indicators, the death group had significantly elevated NEUT, TBIL, INR, and PCT levels (<em>P</em> < 0.05), while LYM, PLT, and ALB levels were significantly decreased (<em>P</em> < 0.05). Pearson correlation analysis revealed that age (<em>r</em> = 0.175, <em>P</em> = 0.032), NEUT (<em>r</em> = 0.184, <em>P</em> = 0.024), TBIL (<em>r</em> = 0.272, <em>P</em> = 0.001), and PCT (<em>r</em> = 0.161, <em>P</em> = 0.049) were positively correlated with prognosis, while gender (<em>r</em> = −0.272, <em>P</em> = 0.001), LYM (<em>r</em> = −0.188, <em>P</em> = 0.021), PLT (<em>r</em> = −0.189, <em>P</em> = 0.021), and ALB (<em>r</em> = −0.197, <em>P</em> = 0.015) were negatively correlated. ROC curve analysis revealed that the AUCs for predicting the 12-week prognosis using NEUT, LYM, PLT, ALB, TBIL, and PCT alone were 0.615, 0.696, 0.616, 0.620, 0.671, and 0.608, respectively. When combined, the AUC significantly increased to 0.817 (<em>P</em> < 0.001), with a sensitivity of 79.17 % and a specificity of 76.47 %, indicating that combined indicators can more accurately predict the prognosis of","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 1","pages":"Article 153147"},"PeriodicalIF":2.3,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145712235","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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