ImmunobiologyPub Date : 2025-03-28DOI: 10.1016/j.imbio.2025.152898
Lizhong Zhang , Hongyi Li , Lei Shi , Jie Geng , Haojun Zhang , Haoran Chen , Peng Zhao , Yang Xiao , Jinqi Lu , Zhilun Li , Hongbin Pu , Chuandong Hou , Chenghui Li , Chumeng Gao , Xia Song , Zhuocheng Bao , Bing Zhai , Bo Guo , Bo Yang , Xuechun Lu , Qi Yu
{"title":"Mechanism and Efficacy of Etanercept in Treating Autoimmune-like Manifestations of Coronavirus Disease 2019 in elderly individuals","authors":"Lizhong Zhang , Hongyi Li , Lei Shi , Jie Geng , Haojun Zhang , Haoran Chen , Peng Zhao , Yang Xiao , Jinqi Lu , Zhilun Li , Hongbin Pu , Chuandong Hou , Chenghui Li , Chumeng Gao , Xia Song , Zhuocheng Bao , Bing Zhai , Bo Guo , Bo Yang , Xuechun Lu , Qi Yu","doi":"10.1016/j.imbio.2025.152898","DOIUrl":"10.1016/j.imbio.2025.152898","url":null,"abstract":"<div><div>During the COVID-19 pandemic, extensive research focused on universal treatments, but few studies addressed treatment regimens for elderly patients. This study aimed to evaluate the effects of etanercept, a TNF inhibitor, in elderly individuals with COVID-19 through observational analysis of compassionate use cases. The results showed that after one month of etanercept treatment, clinical indicators such as C-reactive protein, D-dimer, and fibrinogen normalised, whereas the control group receiving conventional treatment did not fully recover. Single-cell sequencing was performed on seven patients treated with etanercept and two uninfected individuals. Based on our data and in conjunction with external data, a comprehensive characterization map involving 400,000 cells was created. Transcriptomic analysis revealed autoimmune-like manifestations in elderly patients, highlighting the importance of immunotherapy. Plasma cells, platelets, and B cells were the most treatment-sensitive cells. Analysis of five drug types, including antiviral, etanercept, glucocorticoids, tocilizumab, and others, showed that tocilizumab was associated with an increased thrombosis risk in elderly patients. Meanwhile, etanercept alleviated autoimmune-like manifestations by inhibiting platelet factor 4 and suppressing TNF-α. Molecular docking showed etanercept's strong affinity (−15.0 kcal/mol) for the spike protein of the SARS-CoV-2 Omicron variant, suggesting it may protect immune-compromised patients. Our findings support etanercept as a potential treatment for elderly COVID-19 patients with autoimmune-like manifestations.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152898"},"PeriodicalIF":2.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143738903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Giardia duodenalis triggered neutrophil extracellular traps in goats","authors":"Xi Jiang , Qiaoyu Li , Rongsheng Huang , Yuxiao Qian, Yuqian Jiang, Tingting Liu, Yiwen Wang, Kairao Hu, Jing Huang, Wenlong Huang, Quan Liu, Zhengkai Wei, Haoji Zhang, Xingang Yu","doi":"10.1016/j.imbio.2025.152894","DOIUrl":"10.1016/j.imbio.2025.152894","url":null,"abstract":"<div><div><em>Giardia duodenalis</em> is a globally distributed zoonotic parasite primarily transmitted through the fecal-oral route, infecting various vertebrates, and the infection of which is prevalent in goats. Immune cells play a crucial role in pathogens invasion, and neutrophil extracellular traps (NETs) released by neutrophils serve as a non-specific defense mechanism against pathogens including parasites. In this study, we investigated the characteristics, components, and molecular mechanisms of goat NETs upon stimulation with <em>G. duodenalis</em> trophozoites. This study demonstrates that <em>G. duodenalis</em> trigger dose-dependent NETs formation in goat neutrophils, composed of DNA, citrullinated histone H3 (CitH3), and neutrophil elastase (NE). Reactive oxygen species (ROS) accumulation synchronizes with NETosis during <em>G. duodenalis</em> infection. Inhibitor experiments confirmed that <em>G. duodenalis</em>-induced NETs and ROS production depend on TLR2/4 signaling and require NADPH oxidase (NOX), ERK<sub>1/2</sub>, and p38 MAPK activation. This work identifies TLR2/4, NOX, ERK<sub>1/2</sub>, and p38 MAPK pathways as key regulators of NETs/ROS coordination during <em>G. duodenalis</em> infection, providing the first evidence of <em>G. duodenalis</em>-triggered NETs in goats. The findings highlight NETs as critical components of anti-<em>G. duodenalis</em> immunity and suggest potential for NETs-targeted therapeutic strategies.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152894"},"PeriodicalIF":2.5,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunobiologyPub Date : 2025-03-25DOI: 10.1016/j.imbio.2025.152897
Malika Tami , Lourdes Hontecillas-Prieto , Daniel García-Domínguez , Rocío Flores-Campos , Teresa Vilariño-García , Flora Sánchez-Jiménez , Pilar Guadix , José L. Dueñas , Carlos Jiménez-Cortegana , Luis de la Cruz-Merino , Antonio Pérez-Pérez , Víctor Sánchez-Margalet
{"title":"Decreased number of myeloid-derived suppressor cells in the placental trophoblast of gestational diabetes mellitus. Possible role of leptin","authors":"Malika Tami , Lourdes Hontecillas-Prieto , Daniel García-Domínguez , Rocío Flores-Campos , Teresa Vilariño-García , Flora Sánchez-Jiménez , Pilar Guadix , José L. Dueñas , Carlos Jiménez-Cortegana , Luis de la Cruz-Merino , Antonio Pérez-Pérez , Víctor Sánchez-Margalet","doi":"10.1016/j.imbio.2025.152897","DOIUrl":"10.1016/j.imbio.2025.152897","url":null,"abstract":"<div><div>Gestational diabetes mellitus (GDM) is the most common complication of pregnancy and significantly increases both maternal and fetal morbidity and mortality. Inflammation is a hallmark of GDM, and placental inflammation may play a key role in the pathophysiology of the disease. Myeloid-derived suppressor cells (MDSCs), which are innate immunosuppressive, are thought to contribute to feto-maternal tolerance. In normal pregnancies, elevated levels of MDSCs have been observed in both peripheral and umbilical cord blood. Our hypothesis postulates that trophoblasts from placentas belonging to women with GDM may have lower levels of MDSCs compared to trophoblasts from placentas originating from healthy pregnancies. Furthermore, since leptin is overexpressed in the placenta of GDM patients, we hypothesized that leptin might contribute to the reduction of MDSCs. To test this, we investigated the in vitro effects of leptin on MDSC levels in isolated peripheral blood leukocytes after 24 h of incubation. Our findings indicate that trophoblasts from placentas from women with GDM contain a lower percentage of MDSCs compared to trophoblasts from healthy pregnancies. In addition, in vitro studies demonstrated that leptin reduces the number of MDSCs in peripheral blood leukocytes.</div><div>In conclusion, MDSCs are decreased in placentas from pregnancies with GDM, and leptin appears to reduce the number of MDSCs in leukocytes isolated in vitro. Increased leptin expression in trophoblasts from placentas of women with GDM may contribute to the lower levels of MDSCs, potentially playing a role in placental inflammation. However, further investigations are required to fully elucidate this mechanism.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152897"},"PeriodicalIF":2.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143715033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunobiologyPub Date : 2025-03-22DOI: 10.1016/j.imbio.2025.152892
Jinguo Wang , Shelley L. Forrest , Sathish Dasari , Hidetomo Tanaka , Ekaterina Rogaeva , M. Carmela Tartaglia , Susan Fox , Anthony E. Lang , Subha Kalyaanamoorthy , Gabor G. Kovacs
{"title":"Investigation of the HLA locus in autopsy-confirmed progressive supranuclear palsy","authors":"Jinguo Wang , Shelley L. Forrest , Sathish Dasari , Hidetomo Tanaka , Ekaterina Rogaeva , M. Carmela Tartaglia , Susan Fox , Anthony E. Lang , Subha Kalyaanamoorthy , Gabor G. Kovacs","doi":"10.1016/j.imbio.2025.152892","DOIUrl":"10.1016/j.imbio.2025.152892","url":null,"abstract":"<div><h3>Objectives</h3><div>Progressive supranuclear palsy (PSP) is a neurodegenerative disease showing pathological tau accumulation in subcortical neurons and glial cells. The human leukocyte antigen (<em>HLA</em>) locus on chromosome 6 is a polymorphic region with complex linkage patterns that has been implicated in several autoimmune and neurological disorders. The <em>HLA</em> locus has not been systematically examined in PSP. It is unclear whether tau and HLA can interact to induce an autoimmune disease mechanism.</div></div><div><h3>Methods</h3><div>We evaluated an autopsy confirmed PSP cohort (<em>n</em> = 44) and compared allele/haplotype frequencies to those of the reference group of a local deceased Canadian donor pool. We performed HLA-Tau peptide binding prediction and modelling of HLA Class II – Tau Peptide interactions.</div></div><div><h3>Findings</h3><div>Odds ratio was 2.94 (95 % CI 1.01 to 8.55; <em>p</em> = 0.047) for <em>DQB1</em>*06:01 allele, and 2.59 (95 % CI 1.39 to 4.83; <em>p</em> = 0.0025) for the narcolepsy-associated haplotype (<em>DRB1</em>*15:01-<em>DQB1</em>*06:02). One patient with 4-repeat tau PSP-type pathology was a carrier of the IgLON5-associated haplotype (<em>DRB1</em>*10:01-<em>DQB1</em>*05:01). HLA-Tau peptide binding prediction and modelling of HLA Class II – Tau Peptide interactions revealed strong-binding tau peptides but not the PSP-protofilament fold for alleles DQA1*<em>01:02-DQB1*</em>06:02 and DQA1*<em>01:03-DQB1*</em>06:01.</div></div><div><h3>Conclusion</h3><div>Our study suggests that epitopes within the tau peptide may bind to HLA alleles that are found in a subset of PSP patients supporting the notion of an autoimmune pathophysiological component. These findings have implications for subtyping and stratifying patients for therapies, including those targeting immune modulation.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152892"},"PeriodicalIF":2.5,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143681932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunobiologyPub Date : 2025-03-21DOI: 10.1016/j.imbio.2025.152893
Jia Huang, Su Min, Ruiyang Hong, Mou Zou, Dongyu Zhou
{"title":"High-dose Vitamin C inhibits PD-L1 expression by activating AMPK in colorectal cancer","authors":"Jia Huang, Su Min, Ruiyang Hong, Mou Zou, Dongyu Zhou","doi":"10.1016/j.imbio.2025.152893","DOIUrl":"10.1016/j.imbio.2025.152893","url":null,"abstract":"<div><div>Vitamin C (VitC) has elicited considerable interest regarding its potential role in cancer therapy; however, its effects on tumor immunity remain unclear. In colorectal cancer (CRC), although anti-PD-1/PD-L1 therapies demonstrate promise, their efficacy is still constrained. Our prior research demonstrated that VitC can inhibit tumor growth by suppressing the Warburg effect. This study aims to explore the effects of high-dose VitC on PD-L1 expression in CRC, focusing on its underlying mechanisms and potential for enhancing immunotherapy. We found that VitC inhibits aerobic glycolysis in HCT116 cells while also downregulating PD-L1 expression. Further investigations indicated that this process is mediated by VitC's activation of AMPK, which downregulates HK2 and NF-κB, ultimately resulting in reduced PD-L1 expression and increased T cell infiltration. Notably, we observed that VitC and the PD-L1 monoclonal antibody atezolizumab exhibit comparable tumor-inhibiting abilities, and their combined use further enhances this efficacy. In conclusion, our results demonstrate that high-dose VitC activates AMPK, downregulates PD-L1 expression, mitigates immune evasion, and suppresses tumor growth. This provides a promising strategy for optimizing immunotherapy in CRC.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152893"},"PeriodicalIF":2.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143681934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunobiologyPub Date : 2025-03-14DOI: 10.1016/j.imbio.2025.152888
Ning Li , Chunhua Zhang , Xiaoyu Li , Shufen Liu , Youhua Xu , Xifei Yang
{"title":"Targeting B7-H3 in solid tumors: Development and evaluation of novel CAR-T Cell therapy","authors":"Ning Li , Chunhua Zhang , Xiaoyu Li , Shufen Liu , Youhua Xu , Xifei Yang","doi":"10.1016/j.imbio.2025.152888","DOIUrl":"10.1016/j.imbio.2025.152888","url":null,"abstract":"<div><div>Ovarian and gastric cancers, representative of many solid tumors, remain among the most challenging malignancies to treat due to limited therapeutic options and poor outcomes at advanced stages. Although immunotherapies have revolutionized cancer treatment, their efficacy in solid tumors has been hindered by issues such as antigen heterogeneity and the immunosuppressive tumor microenvironment. This study presents the development and evaluation of third-generation chimeric antigen receptor T (CAR-T) cells targeting B7-H3, an immune checkpoint molecule widely overexpressed in solid tumors. The B7-H3 CAR-T cells exhibited robust and selective cytotoxicity against B7-H3-positive tumor cells, sparing normal tissues. In preclinical animal models, these cells significantly inhibited tumor growth, demonstrating higher targeting specificity and preferential accumulation in tumor sites. These results highlight B7-H3-targeted CAR-T cells as a potential breakthrough in immunotherapy for solid tumors, offering a foundation for future clinical trials to refine their safety and efficacy.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152888"},"PeriodicalIF":2.5,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143681933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Different doses of hydroxychloroquine regulate the structure of intestinal flora and glycosyltransferase activity in rats with IgA nephropathy","authors":"Lingling Bao, Xueyan Bian, Liling Ren, Sizeng Bao, Aiwei Zhang","doi":"10.1016/j.imbio.2025.152891","DOIUrl":"10.1016/j.imbio.2025.152891","url":null,"abstract":"<div><h3>Background</h3><div>Hydroxychloroquine (HCQ), by virtue of its ability to reduce proteinuria, is an alternative therapy for Immunoglobulin A nephropathy (IgAN). This study investigated the effects of different doses of HCQ on the structure of intestinal flora and glycosyltransferase activity in IgAN rats.</div></div><div><h3>Methods</h3><div>IgAN model rats constructed by treatment of bovine serum albumin, castor oil and lipopolysaccharide were administered with HCQ (18 or 36 mg/kg) by gavage. Then the number of urine erythrocyte and the renal function of rats were evaluated. The levels of galactose-deficient IgA1 (Gd-IgA1), B cell activation factor (BAFF) and C-reactive protein (CRP) in serum and those of inflammatory factors in renal tissue were detected by ELISA. Renal tissue injury and IgA deposition were assessed by histological analysis. The expressions of Core 1 beta1,3-galactosyltransferase (C1GALT1), Core 1 synthase specific molecular chaperone (COSMC) and ST6 <em>N</em>-acetylgalactosaminide alpha-2,6-sialyltransferase 2 (ST6GALNAC2) were quantified by qRT-PCR, Western blot or in vitro enzyme assays. 16 s rDNA sequencing was used to analyze the structure of intestinal flora in rats.</div></div><div><h3>Results</h3><div>HCQ dose-dependently decreased the levels of serum creatinine, UREA, Gd-IgA1, BAFF, CRP and urine protein, waned the number of urine erythrocyte, inhibited the expressions of inflammatory factors and IgA deposition in renal tissue, and up-regulated the expressions of C1GALT1, COSMC and down-regulated ST6GALNAC2 expression in peripheral blood mononuclear cells (PBMCs).</div></div><div><h3>Conclusion</h3><div>HCQ could reduce glomerular swelling in mesangial area and improve the imbalance of intestinal flora in IgAN rats.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152891"},"PeriodicalIF":2.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunobiologyPub Date : 2025-03-12DOI: 10.1016/j.imbio.2025.152889
Xinran Gao , Haoran Qiao
{"title":"Suppression of astrocyte elevated gene-1 protects against light-induced photoreceptor apoptosis and inflammation in retina","authors":"Xinran Gao , Haoran Qiao","doi":"10.1016/j.imbio.2025.152889","DOIUrl":"10.1016/j.imbio.2025.152889","url":null,"abstract":"<div><h3>Purpose</h3><div>To research the function of astrocyte elevated gene-1 (AEG-1) in light-induced retinal degeneration.</div></div><div><h3>Methods</h3><div>The retinas of BALB/c mice and 661W cells damage were induced by exposure to light; Lipopolysaccharide (LPS) was used to stimulate BV2 cells. AEG-1 siRNA transfection was used to inhibit AEG-1. Expressions of AEG-1, TLR4, TNF-α, phosphor-NF-κB (p-NF-κB) and total NF-κB (t-NF-κB) were detected. Photoreceptor apoptosis was evaluated by flow cytometry or TUNEL. Histological analyses were performed by hematoxylin and eosin (HE) staining.</div></div><div><h3>Results</h3><div>AEG-1 was highly expressed in light damaged (LD) retinas. The photoreceptor apoptosis and the thinning of outer nuclear layer (ONL) were inhibited by AEG-1 siRNA in LD mice retinas. The AEG-1 siRNA pretreatment significantly down-regulated the elevated expression levels of TLR4, p-NF-κB and TNF-α induced by LD in retinas. In vitro, AEG-1 was upregulated in 661W cells induced by LD and in BV2 cells stimulated by LPS. The AEG-1 siRNA prevented light induced apoptosis of 661W cells, and down-regulated the elevated expressions of TLR4, p-NF-κB and pro-inflammatory cytokine TNF-α caused by LPS in BV2 cells.</div></div><div><h3>Conclusions</h3><div>AEG-1 is highly expressed in retinal degeneration caused by LD. Suppression of AEG-1 protects against photoreceptor apoptosis and rescues the thinning of ONL in LD retinas. Suppression of AEG-1 also diminishes inflammation in light induced retinal degeneration, which may be regulated through the NF-κB pathway. Therefore, AEG-1 perhaps become a potential therapeutic target for this type of retinal degenerative disease.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152889"},"PeriodicalIF":2.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143636941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunobiologyPub Date : 2025-03-06DOI: 10.1016/j.imbio.2025.152887
Zannatun Noor , Shaumik Islam , Md. Mehedi Hasan , Ar-Rafi Khan , Md Amran Gazi , Farzana Hossaini , Rashidul Haque , Tahmeed Ahmed , Mustafa Mahfuz
{"title":"Assessment of cellular immune phenotype of peripheral blood mononuclear cells in Bangladeshi children with severe acute malnutrition","authors":"Zannatun Noor , Shaumik Islam , Md. Mehedi Hasan , Ar-Rafi Khan , Md Amran Gazi , Farzana Hossaini , Rashidul Haque , Tahmeed Ahmed , Mustafa Mahfuz","doi":"10.1016/j.imbio.2025.152887","DOIUrl":"10.1016/j.imbio.2025.152887","url":null,"abstract":"<div><div>Children suffering from severe acute malnutrition (SAM) have a weakened immune system. The relationship between malnutrition and alterations in the frequency of peripheral blood mononuclear cells (PBMCs) remains unclear. This study investigated the altered immune responses in Bangladeshi children with SAM compared to healthy children. PBMCs were collected from 24 healthy children and 25 children with SAM upon their hospital admission and after 21 days of nutritional therapy at a nutritional rehabilitation unit. Flow cytometry was employed to assess various subsets of T cells, B cells, and natural killer (NK) cells. Children with SAM exhibited significantly lower levels of activated (CD25+) B cells (SAM vs. healthy: 0.18 % vs. 0.30 %, <em>p</em> = 0.031) and NK cells (SAM vs. healthy: 4.9 % vs. 9.6 %, <em>p</em> = 0.003) compared to healthy controls. Similar immune responses were observed in SAM children during both hospitalization and discharge, with NK cell percentages showing slight increases but remaining significantly lower than in healthy children (SAM endline vs. healthy: 5.9 % vs. 9.6 %, <em>p</em> = 0.032). Notable reductions were also observed in CD62+ helper T cells, CD62L+ cytotoxic T cells, and CD62L+ B cells. These results suggest that although SAM children recover clinically, their immune systems remain compromised during discharge.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152887"},"PeriodicalIF":2.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunobiologyPub Date : 2025-03-06DOI: 10.1016/j.imbio.2025.152885
Yin-hong Zhang , Juan Chen , Wen-fei Mao , Li-xi Yan , Fei Long , Sheng-hao Li , Rui-xian Zhang
{"title":"Harnessing miR-16-5p-Loaded Exosomes from Adipose-Derived Stem Cells to Restore Immune Homeostasis in SLE Patients","authors":"Yin-hong Zhang , Juan Chen , Wen-fei Mao , Li-xi Yan , Fei Long , Sheng-hao Li , Rui-xian Zhang","doi":"10.1016/j.imbio.2025.152885","DOIUrl":"10.1016/j.imbio.2025.152885","url":null,"abstract":"<div><h3>Background</h3><div>Systemic Lupus Erythematosus (SLE) is an autoimmune disorder marked by an imbalance between pro-inflammatory Th17 cells and regulatory T cells (Tregs), which contributes to chronic inflammation and multi-organ damage, necessitating novel therapeutic strategies.</div></div><div><h3>Methods</h3><div>This study investigates the potential of adipose-derived stem cell (ADSC) exosomes to modulate the Th17/Treg balance in SLE patients through the miR-16-5p/LATS1 axis. Flow cytometry, ELISA, and quantitative real-time PCR were utilized to assess immune cell populations and cytokine levels in SLE patients. Additionally, ADSC exosomes were isolated and characterized, and their impact on CD4+ T cells was evaluated using dual-luciferase and Western blot assays.</div></div><div><h3>Results</h3><div>SLE patients exhibited increased Th17 cells and decreased Tregs, with corresponding changes in cytokine levels. Reduced miR-16-5p expression was noted in CD4+ T cells, correlating positively with Treg proportions. ADSC-derived exosomes were shown to deliver miR-16-5p effectively, targeting and downregulating LATS1 expression. This modulation restored the Th17/Treg balance and adjusted cytokine expression, indicating an immune regulatory effect.</div></div><div><h3>Conclusion</h3><div>ADSC-derived exosomes, through the miR-16-5p/LATS1 axis, offer a promising therapeutic approach for SLE by restoring immune equilibrium. This study highlights the potential of exosome-based therapies in modulating immune responses, providing a foundation for developing innovative treatments for autoimmune diseases.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152885"},"PeriodicalIF":2.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143580566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}