Immunologic Research最新文献

{"title":"Assessment of antipsoriatic potential of novel pemetrexed disodium-loaded transdermal patches in an imiquimod-induced mouse model.","authors":"Tejpal Yadav, Hemant Kumar Singh Yadav, Ritu Gilhotra","doi":"10.1007/s12026-025-09635-4","DOIUrl":"https://doi.org/10.1007/s12026-025-09635-4","url":null,"abstract":"<p><p>Psoriasis is a chronic autoimmune skin disorder characterized by keratinocyte hyperproliferation, inflammation, and angiogenesis, significantly impacting patients' quality of life. Current therapeutic strategies, including topical corticosteroids, phototherapy, and systemic biologics, often present limitations such as adverse effects, high costs, and inadequate skin penetration. Transdermal drug delivery offers a promising alternative by enhancing localized drug bioavailability and minimizing systemic side effects. In this study, we investigated the antipsoriatic potential of pemetrexed disodium, a multitargeted antifolate agent, formulated as a transdermal patch in an imiquimod-induced psoriasis mouse model. The patches were prepared using a solvent evaporation technique and optimized for controlled drug release. Mice treated with pemetrexed-loaded transdermal patches exhibited significant dose-dependent reductions in psoriasis severity, as evidenced by improvements in Psoriasis Area and Severity Index (PASI) scores, histopathological analysis, and suppression of inflammatory cytokines (TNF-α, IL-6) assessed via qRT-PCR and ELISA. The highest concentration (0.16 mg/cm²) demonstrated the most pronounced therapeutic effects, comparable to the standard ketoconazole treatment. These findings highlight the potential of pemetrexed disodium-loaded transdermal patches as an innovative, targeted therapy for psoriasis, warranting further clinical investigations.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"81"},"PeriodicalIF":3.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998460","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}

{"title":"Chrysin-loaded poly (lactic-co-glycolic acid) nanoparticles alleviate sepsis-induced splenic injury by regulating myeloid-derived suppressor cells.","authors":"Islam Ahmed Abdelmawgood, Abeer Mahmoud Badr, Asmaa Elsayed Abdelkader, Noha A Mahana, Ayman Saber Mohamed, Hadeer Hesham Abdelfattah","doi":"10.1007/s12026-025-09634-5","DOIUrl":"https://doi.org/10.1007/s12026-025-09634-5","url":null,"abstract":"<p><p>Sepsis is a serious condition resulting from a dysregulated immune-mediated response to an infection. Myeloid-derived suppressor cells (MDSCs) aggregate and serve a protective function in the pathophysiology of lipopolysaccharide (LPS) shock. However, the regulation of MDSCs by chrysin-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (CHR-NP) remains unexplored. CHR-NP was synthesized and characterized by Fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), zeta potential, and dynamic light scattering (DLS). Before being given an intraperitoneal injection of 10 mg/kg of LPS, C57BL/6 mice were given CHR (50 mg/kg), PLGA (50 mg/kg), CHR-NP (50 mg/kg), and dexamethasone (Dexa) (5 mg/kg) by oral administration for 6 days. CHR-NP effectively mitigated LPS-induced splenic injury by diminishing inflammation and oxidative stress. The CHR-NP treatment lowered the amount of malondialdehyde (MDA) and raised the levels of antioxidants like glutathione (GSH), catalase (CAT), and glutathione peroxidase (GPx). Besides that, it stopped the production of cytokines that cause inflammation (tumor necrosis factor (TNF)-α, IL-1β, interferon (IFN)-γ, and IL-12) and increased the production of cytokines that stop inflammation (IL-10 and IL-4). This study demonstrates that CHR-NPs confer significant protective effects against LPS-induced sepsis by modulating immune responses, reducing oxidative stress, and alleviating splenic injury. The ability of CHR-NP to enhance antioxidant defenses, suppress pro-inflammatory cytokines, and promote anti-inflammatory mediators highlights its potential as a novel therapeutic approach for regulating MDSCs and mitigating sepsis-related immunopathology.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"80"},"PeriodicalIF":3.3,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010889","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}

{"title":"Characterization of anti-neutrophil extracellular traps (NET) antibodies according to systemic lupus erythematosus clinical phenotypes.","authors":"Daniel Alberto Carrillo-Vázquez, Jennifer Tiaré Balderas-Miranda, Rosa Icela Arvizu Rivera, Alfredo Pérez-Fragoso, Beatriz Alcalá-Carmona, Miroslava Nuñez-Aguirre, Ana Sofía Vargas-Castro, Abdiel Absalón-Aguilar, Jaquelin Lira-Luna, Nancy R Mejía-Domínguez, Guillermo Juárez-Vega, Karina Santana-de Anda, Jiram Torres-Ruiz, Diana Gómez-Martín","doi":"10.1007/s12026-025-09636-3","DOIUrl":"https://doi.org/10.1007/s12026-025-09636-3","url":null,"abstract":"<p><p>Anti-neutrophil extracellular traps (NETs) antibodies have been observed in patients with lupus nephritis and may contribute to the pathogenic role of NETs in patients with systemic lupus erythematosus (SLE). However, the prevalence of anti-NETs antibodies and their relationship with clinical features of patients with SLE have not been thoroughly studied, which is the aim of this study. Eighty-seven patients who fulfilled the 2019 EULAR/ACR Classification criteria for SLE were included. Plasmatic neutrophil elastase-DNA complexes as NETs remnants and the IgG anti-NETs antibodies were quantified by ELISA in the same sample. Thirty-one (35.6%) patients had positive anti-NETs antibodies. Patients with anti-NETs antibodies were younger at the time of recruitment (28.7 years (23.8-33.2) vs. 35.58 (27.88-45.77), p = 0.003) and had more prominent serological disease activity, with a higher prevalence of positive anti-double stranded (ds)-DNA antibodies (29 (93.5%) vs. 41 (73.2%), p = 0.022), higher titers (148.2 mg/dL vs. 35.6 mg/dL, p = 0.015), and lower levels of C3 and C4 (58 (37-85.5) vs. 77 (54-127), p = 0.017) and C4 (8 (8-12.5) vs. 20 (9-27), p < 0.001). From all clinical manifestations present at the time of recruitment, serositis showed a trend towards anti-NETs positivity (p 0.06). The global SLEDAI-2 K score was higher in the patient's IgG anti-NETs antibodies positive (13 (6.5-18) vs. 6 (4-15), p = 0.042). Anti-NETs antibodies were positively correlated with the systemic lupus erythematosus disease activity index (SLEDAI-2 K) score as well as with the titers of anti-dsDNA antibodies. IgG anti-NET antibodies were found in one-third of SLE patients. This is the first description of the association between IgG anti-NET and clinical features of SLE. Their characterization might allow us to address their role as potential novel biomarkers.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"79"},"PeriodicalIF":3.3,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010074","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}

{"title":"MOSPD2 regulates the activation state of αLβ2 integrin to control monocyte migration: applicability for treatment of chronic inflammatory diseases.","authors":"Yaniv Salem, Niva Yacov, Pinhas Kafri, Oshrat Propheta-Meiran, Arnon Karni, Nitsan Maharshak, Victoria Furer, Ori Elkayam, Itzhak Mendel","doi":"10.1007/s12026-025-09633-6","DOIUrl":"https://doi.org/10.1007/s12026-025-09633-6","url":null,"abstract":"<p><p>Monocytes are innate immune cells that drive the chronicity of various inflammatory diseases. Monocyte migration to inflamed tissues involves multiple steps of interaction with the vascular endothelium and the extracellular matrix (ECM), a process mediated through conformational transitions in cell surface integrins. We previously described motile sperm domain-containing protein 2 (MOSPD2) as a surface protein expressed on myeloid cells that is essential for the migration of monocytes and a key regulator of inflammation. Investigating MOSPD2's mechanism of action, we assessed whether it plays a role in regulating integrin activation and monocyte adhesion. Data show that silencing of MOSPD2 expression in the THP-1 monocytic cell line significantly increased cell adhesion to various ECM molecules. Employing IW-601, a humanized anti-human MOSDP2 monoclonal antibody, on primary human monocytes increased adhesion to ECM molecules as well as to adhesion molecules. At the molecular level, silencing of MOSPD2 or blocking MOSPD2 using IW-601 led to a transition in integrin αLβ2 (CD11a/CD18, LFA-1) conformation into an active high-affinity binding form and to the induction of adhesion-associated signaling pathways. Co-immunoprecipitation experiments showed that MOSPD2 binds integrin-β2 (CD18), but not integrin-β1 (CD29). Our results reveal a novel mechanism controlling monocyte migration, in which MOSPD2 acts as an adhesion checkpoint that governs the balance between monocyte adhesion and release. By demonstrating the inhibitory effect of IW-601 on the migration of primary monocytes isolated from patients with chronic inflammatory diseases, we provide proof of concept for translating MOSPD2's mechanism into a potential treatment for inflammatory diseases, further supported by in vivo data in models of RA and IBD.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"78"},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12045827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010984","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":"Study of immunological and inflammatory gene response in Indian cohort of COVID- 19 patients by NanoString technology.","authors":"Sudarson Sundarrajan, K N Sridhar, Manju Moorthy, Gopalakrishna Ramaswamy","doi":"10.1007/s12026-025-09626-5","DOIUrl":"https://doi.org/10.1007/s12026-025-09626-5","url":null,"abstract":"<p><p>COVID- 19, which has affected millions of people across the globe as a pandemic, is caused by the SARS-Cov- 2 virus which has a case fatality rate of 2.3%. The clinical outcome of those who had mild and severe infection exhibited different responses for the treatment due to differences in the host immune system. Predicting immune response with reliable biomarkers to monitor the severity and also identifying potential biomarkers that could help the clinician in decision-making would be important and also beneficial for the management of COVID- 19 in the hospital setup. In our study, we have used the NanoString nCounter gene expression assay to investigate the molecular signalling of host to COVID- 19 infection. The nCounter gene expression assay identified 29 genes that were differentially regulated and specific to COVID- 19 infection; out of which, 9 genes (ICAM3, PTAFR, CEACAM6, GBP1, C7, STAT1, CEACAM8, IL16, HLA-DPB1) exhibited strong predictive performance to differentiate COVID- 19 infection from healthy controls (AUC ≥ 0.9). We also observed that three genes (MAP4 K1, CTLA4, and HLA-DQB1) were able to differentiate COVID- 19 from patients with flu-like symptoms. A group of 11 genes (C2, CD14, CDKN1 A, CMKLR1, CYBB, HLA-A, IFNA2, LAG3, MARCO, TLR7, and IL15) showed a dysregulation trend with onset of COVID- 19 infection and settled to normal levels by day 14 as patient recovered. The outcome of our study may help in understanding the host immune response towards COVID- 19 infection.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"77"},"PeriodicalIF":3.3,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998499","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}

{"title":"Role of artificial intelligence in advancing immunology.","authors":"Hamad H Alanazi","doi":"10.1007/s12026-025-09632-7","DOIUrl":"https://doi.org/10.1007/s12026-025-09632-7","url":null,"abstract":"<p><p>Artificial intelligence (AI) has revolutionized various biomedical fields, particularly immunology, by enhancing vaccine development, immunotherapies, and allergy treatments. AI helps identify potential vaccine candidates and predict how the body reacts to different antigens based on a vast number of genomic sequences and protein structures. AI can help cancer patients by analyzing their data and offering personalized immunotherapies. AI has also advanced the field of allergy by identifying potential allergens and predicting allergic reactions based on patient genetic and environmental factors. AI could also help diagnose multiple immunological diseases, including autoimmune diseases and immunodeficiencies, by analyzing patient history and laboratory results. AI has deepened our understanding of the human genome by providing numerous amounts of data from DNA sequences previously believed to be nonfunctional. Through machine learning and deep learning, many laborious research tasks, such as screening for DNA mutations, can be efficiently performed in a short amount of time. AI and machine learning are significantly advancing biomedical science in significant areas, including research and industry. This review discusses the latest AI-based tools that can be utilized in the field of immunology. AI tools significantly advance the field of medical research and healthcare by enabling new scientific discoveries and facilitating rapid clinical diagnosis.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"76"},"PeriodicalIF":3.3,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965607","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}

{"title":"The effect of anti-CD20 on inflammation and histopathological alternations in rat photothrombotic ischemic stroke model.","authors":"Leila Hosseini, Mohammad Sadegh Soltani-Zangbar, Nasrin Abolhasanpour, Maryam Hosseini, Aref Delkhosh, Sanam Dolati, Amir Mehdizadeh, Seyed Zanyar Athari, Reza Rikhtegar, Hossein Alikhaniha, Fatemeh Babaei, Mohammad Bagher Pirouzpanah, Mehdi Yousefi","doi":"10.1007/s12026-025-09630-9","DOIUrl":"https://doi.org/10.1007/s12026-025-09630-9","url":null,"abstract":"<p><p>Ischemic stroke (IS) has remained the main cause of mortality and neurological disabilities worldwide. Anti-CD20 treatments have a potent anti-inflammatory effect. Here, we investigated the effect of anti-CD20 on IS-induced inflammation and histopathologic changes in the rat model. Male Sprague-Dawley rats were divided into three groups: control, sham, and stroke. Rats in the stroke groups underwent photothrombosis-induced IS in the sensorimotor cortex area. They were divided into the following subgroups: treated with anti-CD20 after ischemia and killed after 5 and/or 10 days of IS. Histological changes were assessed by hematoxylin and eosin staining. mRNA levels of inflammation markers (VIM, ANXA3, SLC22 A4, and ADM), and also levels of transcription factors for Th1, Th2, and Th17 subsets (Tbet, GATA3, and ROR-γ, respectively), and also Foxp3 were detected in the peripheral blood mononuclear cells by quantitative real-time PCR. The levels of ADM and SLC22 A4 increased following IS on the 5th and 10th days, while treatment with anti-CD20 reversed their levels. Anti-CD20 therapy attenuated inflammation through down-regulation of VIM and ANXA3 after 10 days. This therapeutic effect was mainly mediated by the downregulation of Th1-Th17-driven inflammatory responses (Tbet and RORγt) and the upregulation of Th2 activities (GATA- 3). In addition, anti-CD20 increased the expression of Foxp3. Anti-CD20 treatment can also reduce brain tissue damage after 10 days. Our data showed that inflammation and histopathological alterations are associated with the photothrombotic model of IS, while treatment with anti-CD20 could reduce inflammation and alleviate histopathological changes.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"75"},"PeriodicalIF":3.3,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006859","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}

{"title":"The urease E subunit vaccine stimulate the immune response versus Helicobacter pylori in animal model.","authors":"Maedeh Nikzad-Chaleshtori, Mohsen Asgari, Golnoosh Rezaeizadeh, Faranak Aali, Abbas Doosti","doi":"10.1007/s12026-025-09625-6","DOIUrl":"https://doi.org/10.1007/s12026-025-09625-6","url":null,"abstract":"<p><p>There is a strong association between Helicobacter pylori (H. pylori) and the occurrence of gastritis and gastric mucosal lymphoma in the human population. Vaccination is a viable preventive measure in light of the escalating issue of antibiotic resistance. The use of DNA vaccines presents a potentially effective approach. This study used the utilization of antigenic H. pylori urease E subunit (UreE) for the development of a DNA vaccine. The UreE gene was chemically cloned into pIRES2-DsRed-Express (pDNA), and PCR and restriction enzyme digestion verified the cloning. The immunogenicity and immune-protective efficacy of the vaccination were assessed in BALB/c mice. In contrast, blood samples from BALB/c mice inoculated with pDNA-UreE showed higher levels of IgG, IFN-γ, IL- 4, and IL- 17. Furthermore, stomach damage and bacterial loads were reduced, and BALB/c mice inoculated with pDNA-UreE exhibited a significant protection rate (87.5%) against the H. pylori challenge. pDNA-UreE generated a combination of Th1-Th2-Th17 immune responses, perhaps contributing to adequate protection. Based on our findings, using this DNA immunization as a preventive measure against H. pylori infection is a viable approach.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"74"},"PeriodicalIF":3.3,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014778","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}

{"title":"Immunomodulatory effects of alexidine dihydrochloride on mammalian macrophages through the modulation of the JNK pathway.","authors":"Begüm Rana Atalay, Ömer Mete Başkan, Semanur Ercan, Ece Aydın, Furkan Ayaz, Esra Aydemir","doi":"10.1007/s12026-025-09631-8","DOIUrl":"https://doi.org/10.1007/s12026-025-09631-8","url":null,"abstract":"<p><p>A plethora of the cancer drugs with high therapeutic potential cannot pass the clinical trials because of their immunotoxic activities. In this study, we tested the immunomodulatory and immunostimulatory effects of the anticancer agent alexidine dihydrochloride on J774.2 macrophage cell lines in vitro. The production levels of the pro-inflammatory cytokines (TNF-α, IL-6, GM-CSF, IL-12p40) were measured and compared by ELISA method. The activated (phosphorylated) JNK protein levels were measured by flow cytometer and the possible related intracellular signaling pathway was examined in this way. According to our results, alexidine dihydrochloride has an anti-inflammatory effect on the LPS-stimulated macrophage cell lines, as evidenced by reduced cytokine production compared to controls. Furthermore, its intracellular mechanism of action was found to be mediated partially through JNK signaling pathways. These findings suggest that alexidine dihydrochloride, while being an effective anticancer agent, may also modulate immune responses by dampening excessive inflammation. In this study, determining the anti-inflammatory effect of alexidine dihydrochloride on the immune system will seriously shed light on the role of this anticancer agent in future clinical studies and will provide a serious basis. In summary, the effects of the most drug-active ingredients on the inflammatory response in immune system cells have not been fully tested, and this creates the problem of many drugs failing in clinical studies or lack of knowledge on their side effects. Our study aimed to determine the effect of alexidine dihydrochloride, used as an anticancer agent, on the inflammatory response in J774.2 macrophage cell lines. Future studies with more immune system cells and a wider analysis of the intracellular signaling pathways will be informative about the immunotoxicity of the drug molecule. Future research involving a broader range of immune cell types and a more comprehensive analysis of intracellular signaling pathways will help clarify the immunotoxicity profile of this anticancer agent.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"73"},"PeriodicalIF":3.3,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994519","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}

{"title":"Baicalin restores innate lymphoid immune imbalance during exacerbation of COPD.","authors":"Xuemei Liu, Ai Luo, Mei Yang, Jian Luo, Huifang Li, Xiaoting Chen, Bing Mao, Hongli Jiang, Wei Liu","doi":"10.1007/s12026-025-09629-2","DOIUrl":"https://doi.org/10.1007/s12026-025-09629-2","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) is characterized by immune dysregulation, including altered innate lymphoid cell (ILC) immune responses, particularly during exacerbations (ECOPD). Baicalin, a natural compound prevalent in various herbal medicines, has shown promise as a therapeutic candidate in ECOPD. However, its potential and molecular mechanism for addressing ILC immune imbalance during ECOPD remain poorly understood. First, this study conducted a cross-sectional analysis of ILC immune responses in stable COPD patients and those experiencing exacerbations. Then, clinical findings of skewed ILC immunity were validated in cigarette smoke and lipopolysaccharide-induced ECOPD mouse models. Lastly, the therapeutic effect of baicalin on restoring ILC immune homeostasis was investigated in experimental ECOPD mouse models. Significant downregulation of ILC2 immunity was observed during COPD exacerbations, accompanied by increased ILC1 and ILC3 responses, particularly in cases associated with bacterial infections. Notably, elevated IL-22 levels were observed in this group. Administration of recombinant IL-22 in ECOPD mouse models disrupted lung ILC homeostasis, specifically inhibiting the accumulation of ILC2. Proteomics and transcriptomics analyses suggested IL-22 as a mediator of type 2 immune suppression by creating a molecular environment that favors type 1 and type 3 immunity. Treatment with baicalin effectively restored ILC2 immunity by enhancing the recruitment and activation of lung ILC2 while suppressing ILC1 and ILC3 responses. Importantly, baicalin attenuated IL-22 production from lung ILC3, highlighting its potential as an IL-22 inhibitor. Baicalin demonstrates potential as a therapeutic strategy for addressing ILC immune imbalance in COPD exacerbations, particularly by restoring ILC2 immunity and partially inhibiting IL-22 production. Clinical registration The cross-sectional study was registered with the Chinese Clinical Trial Registry (ChiCTR2100050683).</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"71"},"PeriodicalIF":3.3,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12000166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998542","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}