Pub Date : 2026-02-05DOI: 10.1016/j.cyto.2026.157125
Zhi Li, Mingcai Li, Yan Li
Interleukin (IL)-41, a newly identified cytokine also categorized as an adipokine, was previously known by several names, including Metrnl, Cometin, and Subfatin. IL-41 is ubiquitously expressed throughout the body, with particularly high concentrations in the skin, mucosa, and white adipose tissue. This review consolidates current knowledge on IL-41, emphasizing its dual roles in metabolic regulation, such as glucose homeostasis and adipose tissue browning, as well as immune modulation. Evidence suggests its protective functions in various contexts, including inflammatory injuries, allergic diseases, and cardiometabolic disorders. We examine its potential signaling pathways and associations with diverse diseases, and outline unresolved questions and future research directions. The collective findings highlight the significant potential of IL-41 as a novel biomarker and therapeutic target for inflammation and immune-related diseases.
{"title":"The emerging role of interleukin-41: a novel biomarker and therapeutic target in inflammation and immune-related diseases.","authors":"Zhi Li, Mingcai Li, Yan Li","doi":"10.1016/j.cyto.2026.157125","DOIUrl":"https://doi.org/10.1016/j.cyto.2026.157125","url":null,"abstract":"<p><p>Interleukin (IL)-41, a newly identified cytokine also categorized as an adipokine, was previously known by several names, including Metrnl, Cometin, and Subfatin. IL-41 is ubiquitously expressed throughout the body, with particularly high concentrations in the skin, mucosa, and white adipose tissue. This review consolidates current knowledge on IL-41, emphasizing its dual roles in metabolic regulation, such as glucose homeostasis and adipose tissue browning, as well as immune modulation. Evidence suggests its protective functions in various contexts, including inflammatory injuries, allergic diseases, and cardiometabolic disorders. We examine its potential signaling pathways and associations with diverse diseases, and outline unresolved questions and future research directions. The collective findings highlight the significant potential of IL-41 as a novel biomarker and therapeutic target for inflammation and immune-related diseases.</p>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"200 ","pages":"157125"},"PeriodicalIF":3.7,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146130560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-03DOI: 10.1016/j.cyto.2026.157123
Ruolin Chen , Xiaoxue Jiang , Yuxi Wang , Zhiyuan Shi , Xinyi Liu , Duo Meng , Xian Jiang , Jinpeng Lv , Yan Cao
Vitiligo, a common autoimmune dermatosis, has a pathogenesis hypothesized to involve oxidative stress-induced immune-mediated melanocyte death. However, the role of oxidative stress in triggering autoimmunity during the early stages of vitiligo, along with its regulatory mechanisms and complex interactions, remains incompletely understood. Keratinocytes, as key initiating cells in vitiligo, secrete various chemokines, primarily C-X-C motif ligand 9 and 10 (CXCL9,10), under oxidative stress to recruit autoreactive immune cells targeting melanocytes. Hypoxia-inducible factor-1α (HIF-1α), a highly conserved transcription factor sensitive to oxidative stress, has been revealed to orchestrate cytokine expression and cellular immune functions. Based on this, the present study investigated the association between oxidative stress and HIF-1α in keratinocytes, and elucidated HIF-1α as a critical molecule bridging oxidative stress and autoimmunity in vitiligo. We initially observed significantly elevated HIF-1α levels in both the serum and depigmented lesions of vitiligo patients. Mechanistically, we demonstrates that HIF-1α serves as a potential biomarker associated with vitiligo progression, and through binding to the respective promoters of CXCL9 and CXCL10, regulates their expression and secretion in keratinocytes at the transcriptional level under oxidative stress, thus motivating peripheral blood mononuclear cells (PBMCs) migration to potential downstream melanocyte damage. HIF-1α activation further amplifies cellular oxidative stress damage in keratinocytes, collectively exacerbating the pathogenesis process of vitiligo. Our fundings suggest that the HIF-1α-CXCL9/10 pathway represents a promising therapeutic target for counteracting abnormal immune activation under oxidative stress in vitiligo.
{"title":"Oxidative stress activates HIF-1α to mediate the secretion of CXCL9 and CXCL10 in keratinocytes and trigger the abnormal immune response in vitiligo","authors":"Ruolin Chen , Xiaoxue Jiang , Yuxi Wang , Zhiyuan Shi , Xinyi Liu , Duo Meng , Xian Jiang , Jinpeng Lv , Yan Cao","doi":"10.1016/j.cyto.2026.157123","DOIUrl":"10.1016/j.cyto.2026.157123","url":null,"abstract":"<div><div>Vitiligo, a common autoimmune dermatosis, has a pathogenesis hypothesized to involve oxidative stress-induced immune-mediated melanocyte death. However, the role of oxidative stress in triggering autoimmunity during the early stages of vitiligo, along with its regulatory mechanisms and complex interactions, remains incompletely understood. Keratinocytes, as key initiating cells in vitiligo, secrete various chemokines, primarily C-X-C motif ligand 9 and 10 (CXCL9,10), under oxidative stress to recruit autoreactive immune cells targeting melanocytes. Hypoxia-inducible factor-1α (HIF-1α), a highly conserved transcription factor sensitive to oxidative stress, has been revealed to orchestrate cytokine expression and cellular immune functions. Based on this, the present study investigated the association between oxidative stress and HIF-1α in keratinocytes, and elucidated HIF-1α as a critical molecule bridging oxidative stress and autoimmunity in vitiligo. We initially observed significantly elevated HIF-1α levels in both the serum and depigmented lesions of vitiligo patients. Mechanistically, we demonstrates that HIF-1α serves as a potential biomarker associated with vitiligo progression, and through binding to the respective promoters of CXCL9 and CXCL10, regulates their expression and secretion in keratinocytes at the transcriptional level under oxidative stress, thus motivating peripheral blood mononuclear cells (PBMCs) migration to potential downstream melanocyte damage. HIF-1α activation further amplifies cellular oxidative stress damage in keratinocytes, collectively exacerbating the pathogenesis process of vitiligo. Our fundings suggest that the HIF-1α-CXCL9/10 pathway represents a promising therapeutic target for counteracting abnormal immune activation under oxidative stress in vitiligo.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"200 ","pages":"Article 157123"},"PeriodicalIF":3.7,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-27DOI: 10.1016/j.cyto.2026.157121
Aya A. Abd Elghany , Mostafa M. Kamel Eyada , Shymaa A. Maher , Noha M. Abd El-Fadeal , Lina M. Atef
Background
Alopecia areata (AA) is a common autoimmune disease which causes non-scarring patches of hair loss and has a 2% lifetime risk. Its chronic, recurrent nature makes treatment difficult. Potential roles of the JAK/STAT pathway, long non-coding RNAs (lncRNAs), & microRNAs (miRNAs) are highlighted by recent discoveries on the pathophysiology of alopecia areata (AA).
Method
This case-control study aimed to assess the role of lncRNA H19, miR-29a, and the JAK2/STAT3 pathway in alopecia areata (AA). We enrolled 29 patients and 30 healthy controls, collected venous blood from all participants, and quantified the expression of the target genes using real-time PCR.
Results
Both miR-29a and lncRNA H19 expression were found to be statistically significantly higher in alopecia areata (AA) patients than in the controls (p < 0.05). However, analysis revealed no significant change in the expression of either JAK2 or STAT3 in patients compared to controls.
Conclusion
This study identifies elevated levels of miR-29a and lncRNA H19 in the blood of alopecia areata patients, suggesting their potential role in disease pathophysiology. In contrast, the absence of significant change in JAK2/STAT3 mRNA points to a mechanism independent of transcriptional upregulation for this pathway. To validate these findings, larger, multi-center studies are needed to confirm these peripheral biomarkers in lesional scalp tissue and define the functional lncRNA H19/miR-29a mechanism.
{"title":"Molecular crosstalk between lncRNA H19, miR-29a, and JAK2/STAT3 signaling in alopecia areata: a preliminary study","authors":"Aya A. Abd Elghany , Mostafa M. Kamel Eyada , Shymaa A. Maher , Noha M. Abd El-Fadeal , Lina M. Atef","doi":"10.1016/j.cyto.2026.157121","DOIUrl":"10.1016/j.cyto.2026.157121","url":null,"abstract":"<div><h3>Background</h3><div>Alopecia areata (AA) is a common autoimmune disease which causes non-scarring patches of hair loss and has a 2% lifetime risk. Its chronic, recurrent nature makes treatment difficult. Potential roles of the JAK/STAT pathway, long non-coding RNAs (lncRNAs), & microRNAs (miRNAs) are highlighted by recent discoveries on the pathophysiology of alopecia areata (AA).</div></div><div><h3>Method</h3><div>This case-control study aimed to assess the role of lncRNA H19, miR-29a, and the JAK2/STAT3 pathway in alopecia areata (AA). We enrolled 29 patients and 30 healthy controls, collected venous blood from all participants, and quantified the expression of the target genes using real-time PCR.</div></div><div><h3>Results</h3><div>Both miR-29a and lncRNA H19 expression were found to be statistically significantly higher in alopecia areata (AA) patients than in the controls (<em>p</em> < 0.05). However, analysis revealed no significant change in the expression of either JAK2 or STAT3 in patients compared to controls.</div></div><div><h3>Conclusion</h3><div>This study identifies elevated levels of miR-29a and lncRNA H19 in the blood of alopecia areata patients, suggesting their potential role in disease pathophysiology. In contrast, the absence of significant change in JAK2/STAT3 mRNA points to a mechanism independent of transcriptional upregulation for this pathway. To validate these findings, larger, multi-center studies are needed to confirm these peripheral biomarkers in lesional scalp tissue and define the functional lncRNA H19/miR-29a mechanism.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"199 ","pages":"Article 157121"},"PeriodicalIF":3.7,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-22DOI: 10.1016/j.cyto.2026.157120
Mengzhu Liu , Nan Jiang , Shiqi Song , Qiang Xu, Ling Wang, Fenglei Wang, Xiaomei Wan, Xiaoyan Sun, Chengye Che
Purpose
This study was designed to systematically investigate the therapeutic efficacy and mechanistic underpinnings of the natural plant-derived anthraquinone glycoside, sennoside A (SA), in fungal keratitis.
Methods
We rigorously assessed the safety and therapeutic efficacy of SA in primary peripheral blood neutrophils, THP-1 macrophages, and mouse corneas. Safety was evaluated using CCK-8 viability assays and corneal fluorescein sodium staining. Therapeutic outcomes and immune responses were determined through clinical scoring, hematoxylin–eosin (H&E) staining, immunofluorescence (IF), myeloperoxidase (MPO) activity assays, and flow cytometry. Anti-inflammatory mechanisms were investigated by quantifying caspase-1 and GSDMD protein expression, together with downstream IL-1β and IL-18 mRNA and protein levels, using quantitative real-time PCR (qRT-PCR), Western blotting, and IF. Meanwhile, we explored the translational potential of combining SA with the antifungal agent natamycin.
Results
SA (100 μg/mL) showed no toxicity to cells, corneas, or organs. It significantly reduced corneal clouding, swelling, and clinical severity scores in infected mice. Treatment also decreased the recruitment of pathogenic immune cells (neutrophils/macrophages) and shifted macrophages toward a repair-promoting phenotype. SA inhibited the caspase-1/GSDMD inflammatory pathway, leading to reduced levels of key inflammatory cytokines (IL-1β, IL-18). When combined with natamycin, SA provided better protection than either treatment alone.
Conclusion
SA effectively mitigated fungal keratitis-induced damage by suppressing harmful inflammation and modulating immune responses. Its synergistic action with existing antifungal therapies underscores its promising clinical potential.
目的系统研究天然植物源蒽醌苷sennoside A （SA）对真菌性角膜炎的治疗作用及其机制基础。方法严格评估SA对原代外周血中性粒细胞、THP-1巨噬细胞和小鼠角膜的安全性和治疗效果。采用CCK-8活力测定和角膜荧光素钠染色评估安全性。通过临床评分、苏木精-伊红（H&；E）染色、免疫荧光（IF）、髓过氧化物酶（MPO）活性测定和流式细胞术来确定治疗结果和免疫反应。通过定量实时荧光定量PCR （qRT-PCR）、Western blotting和IF检测caspase-1和GSDMD蛋白表达以及下游IL-1β和IL-18 mRNA和蛋白水平，研究抗炎机制。同时，我们探索了SA与抗真菌药物纳他霉素联用的翻译潜力。结果sa （100 μg/mL）对细胞、角膜、脏器均无毒性。它显著降低了感染小鼠的角膜混浊、肿胀和临床严重程度评分。治疗还减少了致病性免疫细胞（中性粒细胞/巨噬细胞）的募集，并将巨噬细胞转向促进修复的表型。SA抑制caspase-1/GSDMD炎症通路，导致关键炎症细胞因子（IL-1β, IL-18）水平降低。当与纳他霉素联合时，SA比单独治疗提供更好的保护。结论sa可通过抑制有害炎症和调节免疫反应，有效减轻真菌性角膜炎的损害。它与现有抗真菌疗法的协同作用强调了其良好的临床潜力。
{"title":"Sennoside A alleviates fungal keratitis by modulating inflammation and immune responses through the caspase-1/GSDMD pathway","authors":"Mengzhu Liu , Nan Jiang , Shiqi Song , Qiang Xu, Ling Wang, Fenglei Wang, Xiaomei Wan, Xiaoyan Sun, Chengye Che","doi":"10.1016/j.cyto.2026.157120","DOIUrl":"10.1016/j.cyto.2026.157120","url":null,"abstract":"<div><h3>Purpose</h3><div>This study was designed to systematically investigate the therapeutic efficacy and mechanistic underpinnings of the natural plant-derived anthraquinone glycoside, sennoside A (SA), in fungal keratitis.</div></div><div><h3>Methods</h3><div>We rigorously assessed the safety and therapeutic efficacy of SA in primary peripheral blood neutrophils, THP-1 macrophages, and mouse corneas. Safety was evaluated using CCK-8 viability assays and corneal fluorescein sodium staining. Therapeutic outcomes and immune responses were determined through clinical scoring, hematoxylin–eosin (H&E) staining, immunofluorescence (IF), myeloperoxidase (MPO) activity assays, and flow cytometry. Anti-inflammatory mechanisms were investigated by quantifying caspase-1 and GSDMD protein expression, together with downstream IL-1β and IL-18 mRNA and protein levels, using quantitative real-time PCR (qRT-PCR), Western blotting, and IF. Meanwhile, we explored the translational potential of combining SA with the antifungal agent natamycin.</div></div><div><h3>Results</h3><div>SA (100 μg/mL) showed no toxicity to cells, corneas, or organs. It significantly reduced corneal clouding, swelling, and clinical severity scores in infected mice. Treatment also decreased the recruitment of pathogenic immune cells (neutrophils/macrophages) and shifted macrophages toward a repair-promoting phenotype. SA inhibited the caspase-1/GSDMD inflammatory pathway, leading to reduced levels of key inflammatory cytokines (IL-1β, IL-18). When combined with natamycin, SA provided better protection than either treatment alone.</div></div><div><h3>Conclusion</h3><div>SA effectively mitigated fungal keratitis-induced damage by suppressing harmful inflammation and modulating immune responses. Its synergistic action with existing antifungal therapies underscores its promising clinical potential.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"199 ","pages":"Article 157120"},"PeriodicalIF":3.7,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-20DOI: 10.1016/j.cyto.2026.157119
Isabela Valim Sarmento , Julia Sthefany Zordan Nunes , Bruna Caetano Pimenta , Carlos Henrique Dettmann Fantecelle de Castro , Suwellen Sardinha Dias de Azevedo , Célio Geraldo Freire-de-Lima , Debora Decote Ricardo de Lima , Isabela Ribeiro Rodrigues , Anna Clara Gregório Có , Jaqueline Pegoretti Goulart , Eric Arrivabene Tavares , Edson Delatorre , Rodrigo Ribeiro Rodrigues , Luciana Polaco Covre , Daniel Cláudio Oliveira Gomes
Oropouche virus (OROV), a member of the Peribunyaviridae family, is an emerging arthropod-borne virus that has recently expanded across Brazilian states, establishing new transmission hotspots beyond the Amazon Basin. OROV infection causes an acute febrile illness with symptoms similar to those of other arboviruses. However, recent reports of fatal cases and vertical transmission leading to congenital anomalies have highlighted OROV as an emerging public health concern. In this study, we conducted an in-depth analysis of cytokine networks during acute Oropouche fever in patients with confirmed OROV infection. Using commercial cytokine panels, we quantified circulating inflammatory cytokines and chemokines and evaluated their correlations with viral load (inferred from cycle threshold values). OROV-infected patients exhibited a distinctive cytokine profile, with significant elevations in pro-inflammatory mediators including IL-18, monocyte chemoattractant protein-1, and tendency to increase IFN-α2, whereas IL-33 and TNF-α were reduced compared with healthy controls. Network analysis revealed tightly interconnected cytokines interactions during disease progression. Notably, inflammatory mediator levels did not correlate with viral load, indicating that systemic cytokine responses operate independently of viral replication kinetics. These findings reveal a unique inflammatory signature in OROV infection, suggesting specific pathogenic mechanisms important for understanding disease progression and developing therapeutic strategies.
{"title":"Cytokine profiling in oropouche fever highlights dissociation between systemic immunity and viral load","authors":"Isabela Valim Sarmento , Julia Sthefany Zordan Nunes , Bruna Caetano Pimenta , Carlos Henrique Dettmann Fantecelle de Castro , Suwellen Sardinha Dias de Azevedo , Célio Geraldo Freire-de-Lima , Debora Decote Ricardo de Lima , Isabela Ribeiro Rodrigues , Anna Clara Gregório Có , Jaqueline Pegoretti Goulart , Eric Arrivabene Tavares , Edson Delatorre , Rodrigo Ribeiro Rodrigues , Luciana Polaco Covre , Daniel Cláudio Oliveira Gomes","doi":"10.1016/j.cyto.2026.157119","DOIUrl":"10.1016/j.cyto.2026.157119","url":null,"abstract":"<div><div>Oropouche virus (OROV), a member of the <em>Peribunyaviridae</em> family, is an emerging arthropod-borne virus that has recently expanded across Brazilian states, establishing new transmission hotspots beyond the Amazon Basin. OROV infection causes an acute febrile illness with symptoms similar to those of other arboviruses. However, recent reports of fatal cases and vertical transmission leading to congenital anomalies have highlighted OROV as an emerging public health concern. In this study, we conducted an in-depth analysis of cytokine networks during acute Oropouche fever in patients with confirmed OROV infection. Using commercial cytokine panels, we quantified circulating inflammatory cytokines and chemokines and evaluated their correlations with viral load (inferred from cycle threshold values). OROV-infected patients exhibited a distinctive cytokine profile, with significant elevations in pro-inflammatory mediators including IL-18, monocyte chemoattractant protein-1, and tendency to increase IFN-α2, whereas IL-33 and TNF-α were reduced compared with healthy controls. Network analysis revealed tightly interconnected cytokines interactions during disease progression. Notably, inflammatory mediator levels did not correlate with viral load, indicating that systemic cytokine responses operate independently of viral replication kinetics. These findings reveal a unique inflammatory signature in OROV infection, suggesting specific pathogenic mechanisms important for understanding disease progression and developing therapeutic strategies.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"199 ","pages":"Article 157119"},"PeriodicalIF":3.7,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146016816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-20DOI: 10.1016/j.cyto.2026.157116
Kai Hu , Jiaxin Chen , Bo Yang , Lili Fu , Qing Yao , Jing Xu , Mengjin Li , Nanmei Liu , Cheng Xue , Zhiguo Mao
Background
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst expansion and chronic inflammation. Interleukin-37 (IL-37) is an anti-inflammatory cytokine, but its role in ADPKD remains unclear. This study aimed to evaluate IL-37 expression in ADPKD patients and assess its clinical relevance in disease severity and renal prognosis.
Methods
IL-37 expression in kidney tissues and cell lines was examined by real-time PCR, Western blot, and immunofluorescence. IL-37 levels were measured by ELISA. This retrospective observational cohort study analyzed longitudinal follow-up data of ADPKD patients using Cox proportional hazards models to explore the prognostic value of IL-37 for progression to end-stage kidney disease (ESKD).
Results
78 ADPKD patients and 20 normal controls were included. IL-37 expression was significantly elevated in kidney tissues, cyst fluid, serum, and urine from ADPKD patients compared with normal controls. Urinary IL-37, adjusted for creatinine (uIL-37/uCr), rose with advancing CKD stages, and it showed a positive correlation with tubular injury markers—NGAL, L-FABP, MCP-1, and α1-MG—and a negative correlation with eGFR and hemoglobin levels. After adjusting for baseline eGFR, age, and inflammation-associated biomarkers (MCP1), elevated urinary IL-37 was independently associated with better kidney survival (HR = 0.954, 95% CI: 0.912–0.998, P = 0.041), suggesting a protective role in ADPKD progression.
Conclusions
IL-37 is elevated in ADPKD, reflecting inflammation and tubular injury in disease pathogenesis. Despite higher levels in advanced disease, urinary IL-37 independently predicts better renal survival, suggesting its potential as both a disease activity marker and prognostic indicator.
{"title":"Urinary interleukin-37 as a suggested protective biomarker of renal prognosis in autosomal dominant polycystic kidney disease","authors":"Kai Hu , Jiaxin Chen , Bo Yang , Lili Fu , Qing Yao , Jing Xu , Mengjin Li , Nanmei Liu , Cheng Xue , Zhiguo Mao","doi":"10.1016/j.cyto.2026.157116","DOIUrl":"10.1016/j.cyto.2026.157116","url":null,"abstract":"<div><h3>Background</h3><div>Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst expansion and chronic inflammation. Interleukin-37 (IL-37) is an anti-inflammatory cytokine, but its role in ADPKD remains unclear. This study aimed to evaluate IL-37 expression in ADPKD patients and assess its clinical relevance in disease severity and renal prognosis.</div></div><div><h3>Methods</h3><div>IL-37 expression in kidney tissues and cell lines was examined by real-time PCR, Western blot, and immunofluorescence. IL-37 levels were measured by ELISA. This retrospective observational cohort study analyzed longitudinal follow-up data of ADPKD patients using Cox proportional hazards models to explore the prognostic value of IL-37 for progression to end-stage kidney disease (ESKD).</div></div><div><h3>Results</h3><div>78 ADPKD patients and 20 normal controls were included. IL-37 expression was significantly elevated in kidney tissues, cyst fluid, serum, and urine from ADPKD patients compared with normal controls. Urinary IL-37, adjusted for creatinine (uIL-37/uCr), rose with advancing CKD stages, and it showed a positive correlation with tubular injury markers—NGAL, L-FABP, MCP-1, and α1-MG—and a negative correlation with eGFR and hemoglobin levels. After adjusting for baseline eGFR, age, and inflammation-associated biomarkers (MCP1), elevated urinary IL-37 was independently associated with better kidney survival (HR = 0.954, 95% CI: 0.912–0.998, <em>P</em> = 0.041), suggesting a protective role in ADPKD progression.</div></div><div><h3>Conclusions</h3><div>IL-37 is elevated in ADPKD, reflecting inflammation and tubular injury in disease pathogenesis. Despite higher levels in advanced disease, urinary IL-37 independently predicts better renal survival, suggesting its potential as both a disease activity marker and prognostic indicator.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"199 ","pages":"Article 157116"},"PeriodicalIF":3.7,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146016851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-18DOI: 10.1016/j.cyto.2026.157114
Jingting Mai , Runlu Sun , Wenhao Liu , Xinyu Hu, Ying Yang, Yangxin Chen, Jingfeng Wang
Atherosclerosis is a chronic inflammatory disease driven by pathological angiogenesis and plaque instability. Herein, we investigated the role of macrophage-derived CXCL2 in mediating endothelial progenitor cell (EPC) homing during atherosclerosis progression. Using ApoE−/− mice on a high-fat diet and in vitro co-culture models, we found that infused EPCs exacerbated plaque burden, neovascularization, and matrix degradation. Macrophages were essential for EPC recruitment to plaques. Ox-LDL-stimulated macrophages enhanced EPC angiogenic functions, with transcriptome sequencing identifying CXCL2 as a key upregulated mediator. Functional experiments confirmed CXCL2's critical role. In vivo silencing of CXCL2 attenuated EPC homing, reduced plaque size and lipid accumulation, decreased neovascularization, and stabilized the plaque matrix. Our findings demonstrate that macrophages promote pathological angiogenesis and plaque progression via CXCL2, suggesting that targeting this chemokine could be a novel therapeutic strategy for stabilizing atherosclerotic plaques.
{"title":"Macrophage-mediated CXCL2 regulation of EPC homing promotes the progression of atherosclerosis","authors":"Jingting Mai , Runlu Sun , Wenhao Liu , Xinyu Hu, Ying Yang, Yangxin Chen, Jingfeng Wang","doi":"10.1016/j.cyto.2026.157114","DOIUrl":"10.1016/j.cyto.2026.157114","url":null,"abstract":"<div><div>Atherosclerosis is a chronic inflammatory disease driven by pathological angiogenesis and plaque instability. Herein, we investigated the role of macrophage-derived CXCL2 in mediating endothelial progenitor cell (EPC) homing during atherosclerosis progression. Using ApoE−/− mice on a high-fat diet and in vitro co-culture models, we found that infused EPCs exacerbated plaque burden, neovascularization, and matrix degradation. Macrophages were essential for EPC recruitment to plaques. Ox-LDL-stimulated macrophages enhanced EPC angiogenic functions, with transcriptome sequencing identifying CXCL2 as a key upregulated mediator. Functional experiments confirmed CXCL2's critical role. In vivo silencing of CXCL2 attenuated EPC homing, reduced plaque size and lipid accumulation, decreased neovascularization, and stabilized the plaque matrix. Our findings demonstrate that macrophages promote pathological angiogenesis and plaque progression via CXCL2, suggesting that targeting this chemokine could be a novel therapeutic strategy for stabilizing atherosclerotic plaques.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"199 ","pages":"Article 157114"},"PeriodicalIF":3.7,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146002744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-17DOI: 10.1016/j.cyto.2026.157117
Jingjing Song, Zhen Liu, Xiaohong Xu, Yanni Wang, Fan Yang, Ting Zhang, Yunqing Zhang, Yufei Bi, Zhenglun Pan
Background
Rheumatoid arthritis (RA) is a multifactorial autoimmune disorder characterized by persistent inflammation and joint destruction. Despite advances in understanding RA's immunopathology, its epigenetic regulation remains underexplored, particularly in diverse populations. This study aims to bridge this gap by examining lymphotoxin alpha (LTA) DNA methylation in a Chinese cohort and exploring the relationship with gene polymorphism.
Methods
This study involved 145 RA patients and 140 age-matched healthy controls from Qingdao, China. We analyzed DNA methylation in the LTA gene using bisulfite sequencing and assessed SNP genotypes with high-resolution melting analysis. Statistical correlations were performed using SPSS to link methylation patterns with clinical indicators of RA severity.
Results
Significantly higher methylation levels were observed at several CpG sites within the LTA gene in RA patients compared to controls. These methylation patterns were positively correlated with clinical measures such as erythrocyte sedimentation rate, C-reactive protein and Disease Activity Score-28, suggesting their relevance in RA pathophysiology. The CC genotype of rs2009658 was associated with elevated methylation at multiple CpG sites within the LTA gene, as well as the TT genotype of rs2229094.
Conclusions
LTA DNA methylation is a potential inflammatory indicator and therapeutic target for RA. The rs2009658 CC genotype and rs2229094 TT genotype are susceptible genotypes associated with LTA hypermethylation.
{"title":"Enhanced lymphotoxin alpha DNA hypermethylation and correlation with genetic polymorphism in rheumatoid arthritis among the Chinese population","authors":"Jingjing Song, Zhen Liu, Xiaohong Xu, Yanni Wang, Fan Yang, Ting Zhang, Yunqing Zhang, Yufei Bi, Zhenglun Pan","doi":"10.1016/j.cyto.2026.157117","DOIUrl":"10.1016/j.cyto.2026.157117","url":null,"abstract":"<div><h3>Background</h3><div>Rheumatoid arthritis (RA) is a multifactorial autoimmune disorder characterized by persistent inflammation and joint destruction. Despite advances in understanding RA's immunopathology, its epigenetic regulation remains underexplored, particularly in diverse populations. This study aims to bridge this gap by examining lymphotoxin alpha (LTA) DNA methylation in a Chinese cohort and exploring the relationship with gene polymorphism.</div></div><div><h3>Methods</h3><div>This study involved 145 RA patients and 140 age-matched healthy controls from Qingdao, China. We analyzed DNA methylation in the LTA gene using bisulfite sequencing and assessed SNP genotypes with high-resolution melting analysis. Statistical correlations were performed using SPSS to link methylation patterns with clinical indicators of RA severity.</div></div><div><h3>Results</h3><div>Significantly higher methylation levels were observed at several CpG sites within the LTA gene in RA patients compared to controls. These methylation patterns were positively correlated with clinical measures such as erythrocyte sedimentation rate, C-reactive protein and Disease Activity Score-28, suggesting their relevance in RA pathophysiology. The CC genotype of rs2009658 was associated with elevated methylation at multiple CpG sites within the LTA gene, as well as the TT genotype of rs2229094.</div></div><div><h3>Conclusions</h3><div>LTA DNA methylation is a potential inflammatory indicator and therapeutic target for RA. The rs2009658 CC genotype and rs2229094 TT genotype are susceptible genotypes associated with LTA hypermethylation.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"199 ","pages":"Article 157117"},"PeriodicalIF":3.7,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145974947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-13DOI: 10.1016/j.cyto.2026.157118
Shu Yang , Rui Wang , Hao Li , Xingyong Chen , Jingbo Zhai , Mingdong Huang , Tianbin Chen , Meijuan Huang , Longguang Jiang
Dysregulation of the Ang-Tie pathway drives vascular leakage in sepsis. This study investigates plasma Ang-Tie axis components as sepsis biomarkers in leukemia through a retrospective cohort of 77 patients (36 with sepsis, 41 without sepsis). Septic patients exhibited significantly lower Ang1 (log10: 2.685 vs 3.143 pg/mL) and Tie2 (log10: 2.300 vs 2.800 pg/mL), but higher Ang2 (3.258 vs 2.841 pg/mL) than controls (P < 0.01). Critically, elevated Ang2/Ang1 (1.185 vs 0.917) and Ang2/Tie2 ratios (1.381 vs 0.995) strongly correlated with sepsis susceptibility. The Ang2/Tie2 ratio demonstrated superior diagnostic accuracy (AUC = 0.860, sensitivity = 86.1%, specificity = 80.5%) compared to routine biomarkers (D-dimer, procalcitonin). Strikingly, an Ang2/Tie2 ratio > 1.121 (Youden index) predicted a 3.5-fold increased mortality risk (95% CI: 1.51–8.25), independent of the leukemia subtype or treatment phase. These findings position the Ang2/Tie2 ratio as a dual diagnostic and pro gnostic biomarker for sepsis in leukemia patients, offering a mechanistic link between endothelial injury and poor outcomes. Our work bridges vascular biology and hematologic oncology, providing actionable insights for early intervention and targeted therapies to mitigate vascular leakage in high-risk populations
脓毒症中Ang-Tie通路失调导致血管渗漏。本研究通过77例白血病患者（36例脓毒症，41例非脓毒症）的回顾性队列研究血浆ang -铁轴成分作为白血病脓毒症的生物标志物。脓毒症患者Ang1 （log10: 2.685 vs 3.143 pg/mL）和Tie2 （log10: 2.300 vs 2.800 pg/mL）明显低于对照组，但Ang2 （3.258 vs 2.841 pg/mL）高于对照组（P < 0.01）。至关重要的是，Ang2/Ang1比值（1.185 vs 0.917）和Ang2/Tie2比值（1.381 vs 0.995）升高与脓毒症易感性密切相关。与常规生物标志物（d -二聚体、降钙素原）相比，Ang2/Tie2的诊断准确性更高（AUC = 0.860，敏感性= 86.1%，特异性= 80.5%）。引人注目的是，Ang2/Tie2比值>； 1.121（约登指数）预测死亡风险增加3.5倍（95% CI: 1.51-8.25），与白血病亚型或治疗阶段无关。这些发现将Ang2/Tie2比值定位为白血病患者败血症的双重诊断和预后生物标志物，提供了内皮损伤和不良预后之间的机制联系。我们的工作是血管生物学和血液肿瘤学的桥梁，为早期干预和靶向治疗提供可操作的见解，以减轻高危人群的血管泄漏
{"title":"Elevated plasma Ang2/Tie2 ratio as a diagnostic and prognostic biomarker for sepsis in leukemia patients","authors":"Shu Yang , Rui Wang , Hao Li , Xingyong Chen , Jingbo Zhai , Mingdong Huang , Tianbin Chen , Meijuan Huang , Longguang Jiang","doi":"10.1016/j.cyto.2026.157118","DOIUrl":"10.1016/j.cyto.2026.157118","url":null,"abstract":"<div><div>Dysregulation of the Ang-Tie pathway drives vascular leakage in sepsis. This study investigates plasma Ang-Tie axis components as sepsis biomarkers in leukemia through a retrospective cohort of 77 patients (36 with sepsis, 41 without sepsis). Septic patients exhibited significantly lower Ang1 (log<sub>10</sub>: 2.685 vs 3.143 pg/mL) and Tie2 (log<sub>10</sub>: 2.300 vs 2.800 pg/mL), but higher Ang2 (3.258 vs 2.841 pg/mL) than controls (<em>P</em> < 0.01). Critically, elevated Ang2/Ang1 (1.185 vs 0.917) and Ang2/Tie2 ratios (1.381 vs 0.995) strongly correlated with sepsis susceptibility. The Ang2/Tie2 ratio demonstrated superior diagnostic accuracy (AUC = 0.860, sensitivity = 86.1%, specificity = 80.5%) compared to routine biomarkers (D-dimer, procalcitonin). Strikingly, an Ang2/Tie2 ratio > 1.121 (Youden index) predicted a 3.5-fold increased mortality risk (95% CI: 1.51–8.25), independent of the leukemia subtype or treatment phase. These findings position the Ang2/Tie2 ratio as a dual diagnostic and pro gnostic biomarker for sepsis in leukemia patients, offering a mechanistic link between endothelial injury and poor outcomes. Our work bridges vascular biology and hematologic oncology, providing actionable insights for early intervention and targeted therapies to mitigate vascular leakage in high-risk populations</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"199 ","pages":"Article 157118"},"PeriodicalIF":3.7,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145974563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The purpose of this systematic review and meta-analysis was to summarize the existing evidence of the IL1RN variable number (usually two to six) of tandem repeat (VNTR) polymorphism in modulating the susceptibility to immune thrombocytopenia purpura (ITP), with the aim of clarifying its potential as a genetic marker for disease risk stratification. An extensive literature review was performed utilizing the Cochrane Library, NCBI PubMed, and Clarivate Web of Science databases, covering publications up to October 11, 2025. R language was employed to perform pooled estimation and present the results. The odds ratios and corresponding 95% confidence intervals were estimated to assess the strength of the effect. A total of 12 case-control studies comprising 770 ITP cases and 1424 controls were integrated for further synthetic analyses. Summary estimates in all genetic models suggested that the individuals carrying the variant with two repeats are more susceptible to this hematologic disorder. When stratified by geographic region, only the pooled estimates for Latin American and North African countries were statistically significant. No significant publication bias was evident. In conclusion, this meta-analysis indicated that the IL1RN VNTR polymorphism was significantly associated with ITP susceptibility, particularly in Latin American and North African populations.
本系统综述和荟萃分析的目的是总结现有的IL1RN串联重复序列（VNTR）可变数目（通常为2至6个）多态性在调节免疫性血小板减少性紫癜（ITP）易感性中的证据，目的是阐明其作为疾病风险分层遗传标记的潜力。我们利用Cochrane图书馆、NCBI PubMed和Clarivate Web of Science数据库进行了广泛的文献综述，涵盖了截至2025年10月11日的出版物。采用R语言进行池估计并给出结果。估计比值比和相应的95%置信区间来评估效果的强度。共纳入了12项病例对照研究，包括770例ITP病例和1424例对照，用于进一步的综合分析。所有遗传模型的总结估计表明，携带两个重复变体的个体更容易患这种血液病。当按地理区域分层时，只有拉丁美洲和北非国家的汇总估计值具有统计学意义。没有明显的发表偏倚。总之，这项荟萃分析表明，IL1RN VNTR多态性与ITP易感性显著相关，特别是在拉丁美洲和北非人群中。
{"title":"The interleukin-1 receptor antagonist gene VNTR polymorphism confers a genetic contribution to the risk of immune thrombocytopenia purpura: A systematic review and meta-analysis","authors":"Huifang Wei , Yuyang Xie , Qingyang Huai , Zixiao Hua , Xinyu Yang , Lingxi Chen , Youyi Kong , Wen Xue , Caiming Zhao , Shangshang Gao , Xiaoqin Yang","doi":"10.1016/j.cyto.2026.157112","DOIUrl":"10.1016/j.cyto.2026.157112","url":null,"abstract":"<div><div>The purpose of this systematic review and meta-analysis was to summarize the existing evidence of the <em>IL1RN</em> variable number (usually two to six) of tandem repeat (VNTR) polymorphism in modulating the susceptibility to immune thrombocytopenia purpura (ITP), with the aim of clarifying its potential as a genetic marker for disease risk stratification. An extensive literature review was performed utilizing the Cochrane Library, NCBI PubMed, and Clarivate Web of Science databases, covering publications up to October 11, 2025. R language was employed to perform pooled estimation and present the results. The odds ratios and corresponding 95% confidence intervals were estimated to assess the strength of the effect. A total of 12 case-control studies comprising 770 ITP cases and 1424 controls were integrated for further synthetic analyses. Summary estimates in all genetic models suggested that the individuals carrying the variant with two repeats are more susceptible to this hematologic disorder. When stratified by geographic region, only the pooled estimates for Latin American and North African countries were statistically significant. No significant publication bias was evident. In conclusion, this meta-analysis indicated that the <em>IL1RN</em> VNTR polymorphism was significantly associated with ITP susceptibility, particularly in Latin American and North African populations.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"199 ","pages":"Article 157112"},"PeriodicalIF":3.7,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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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