Frontiers in Immunology最新文献

{"title":"NETs - as predictors and targets of supportive therapy for cancer treatment.","authors":"Maria-Laura Morawiec, Robert Kubina, Ewa Jabłońska, Wioletta Ratajczak-Wrona, Sebastian Stępień, Maciej Gołębski, Aleksandra Mielczarek-Palacz","doi":"10.3389/fimmu.2025.1666261","DOIUrl":"10.3389/fimmu.2025.1666261","url":null,"abstract":"<p><p>NETs are network-like structures consisting mainly of DNA and various proteins released by neutrophils physiologically in response to pathogens. Moreover, according to recent reports, NETs also play an important role in carcinogenesis. They are involved in all stages of carcinogenesis, assist in the process of metastasis, and their presence has been linked to higher mortality and poorer prognosis in numerous cancer types. This review focuses on anti-cancer treatments related to disintegration of existing NETs, inhibition of their formation and regulation of their formation. Cases in which the presence of NETs was associated with anti-cancer activity and the association of NETs with complications co-occurring with cancer or related to cancer treatment was presented. This paper also presents mechanisms of NETs inhibition, predicting the efficacy or resistance of anti-cancer therapy associated with NETs.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1666261"},"PeriodicalIF":5.9,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of donor-specific antibodies with adverse outcomes in solid organ transplantation: A systematic review and meta-analysis of 69 studies.","authors":"Zhong-Yu Kang, Xue-Ya Han, Chun Liu, Wei Liu, Dai-Hong Li","doi":"10.3389/fimmu.2025.1633853","DOIUrl":"10.3389/fimmu.2025.1633853","url":null,"abstract":"<p><strong>Importance: </strong>Preformed donor-specific antibodies (pre-DSAs) are a significant immunologic barrier in solid organ transplantation (SOT), yet their association with post-transplant outcomes lacks consensus, limiting standardized clinical management.</p><p><strong>Objective: </strong>To determine the association between pre-DSA and posttransplant complications, including antibody-mediated rejection (AMR), T cell-mediated rejection (TCMR), graft loss, and patient mortality, with subgroup analyses stratified by organ type and MFI thresholds (1,000 cutoff).</p><p><strong>Data sources: </strong>Systematic review of 3,322 studies from PubMed, Embase and the Cochrane Library (from inception to February 2024) following the PRISMA guidelines.</p><p><strong>Study selection: </strong>Sixty-nine observational studies (22,737 transplant recipients; 3,787 pre-DSAs+), including retrospective and prospective cohorts, encompassing kidney (KT) (41 studies), liver (LT) (13), lung (6), heart (3), and other organ transplants.</p><p><strong>Main outcomes and measures: </strong>Primary: AMR, TCMR, graft loss, patient death.Secondary: Biliary complications, bacteremia, delayed graft function (DGF).</p><p><strong>Results: </strong>Pre-DSAs positivity conferred significantly elevated risks of AMR (RR = 5.21, 95%CI 4.01-6.79), graft loss (RR = 2.11, 1.72-2.60), and mortality (RR = 1.62, 1.39-1.89) compared with pre-DSAs-negative recipients, with marked heterogeneity across organ types. KTs faced the highest risk of AMR risk (RR = 6.09, 4.39-8.46), whereas LT recipients exhibited elevated mortality (RR = 1.81, 1.30-2.53) but lower AMR rates (RR = 1.81 <i>vs</i>. KT). The thoracic organs (heart/lung) had no significant association with AMR (RR1.32, 0.86-2.03). Stratification by MFI thresholds revealed amplified risks at MFI≥1,000, particularly for AMR (RR = 7.51 <i>vs</i> 4.65 at MFI<1,000; Pinteraction<0.001) and loss of graft (RR = 2.30 <i>vs</i> 1.81; P = .032). KT with MFI≥1,000 had the highest cumulative hazards (AMR: RR = 8.12, 5.94-11.10; graft loss: RR = 2.55, 1.98-3.28), whereas LT recipients with MFI≥1,000 had higher mortality RR = 2.01 (1.44-2.80). Secondary outcomes included increased delayed graft function (DGF: RR = 1.49, 1.12-1.98) in pre-DSA+ patients, driven by KT (RR = 1.82, 1.30-2.55), but no association with T-cell-mediated rejection (TCMR: RR = 1.10, 0.94-1.28).</p><p><strong>Conclusions: </strong>Pre-DSAs is a strong independent predictor of AMR and graft loss in SOT, with amplified risks in KT and cohorts with DSA+ MFI≥1,000. These findings advocate for universal pretransplant DSAs screening and DSA+MFI-guided desensitization to prioritize high-risk patients. Organ-specific strategies, intensified AMR surveillance in KTs, and mortality-focused monitoring in LTs, are critical to improving outcomes.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1633853"},"PeriodicalIF":5.9,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Virus-like particles containing the extracellular domain of G protein in combination with a CTL peptide of M2 elicit protection against respiratory syncytial virus infection without pulmonary disease.","authors":"Huan Qin, Jin Luo, Zishu Pan","doi":"10.3389/fimmu.2025.1625670","DOIUrl":"10.3389/fimmu.2025.1625670","url":null,"abstract":"<p><strong>Background and aims: </strong>Respiratory syncytial virus (RSV) is a major respiratory pathogen afflicting both infants and the elderly. Although three RSV vaccines have been approved for adults over the age of 60 or pregnant individuals, there are ongoing efforts to develop novel vaccines against RSV infection. This study was designed to develop and evaluate virus-like particles (VLPs) as potential RSV subunit vaccine candidates, with the goal of balancing immunogenicity, protective efficacy, and safety.</p><p><strong>Methods: </strong>Two types of VLPs were constructed using a recombinant baculovirus (rBV)-insect cell expression system: G_ECD-VLPs (containing the extracellular domain [G_ECD] of RSV G protein) and G_ECD/M2_82-90-VLPs (containing GECD fused with the CTL epitope M2_82-90 of M2 protein). BALB/c mice were vaccinated with these VLPs, and immune responses were assessed via RSV-specific IgG and neutralizing antibody titers, cytokine profiles (IFN-γ, IL-2, TNF-α, IL-10, IL-4, IL-5), and lung T-cell subsets (CD25⁺FoxP3⁺ Treg and Th17 cells). Protective efficacy against RSV infection and immunopathology was further evaluated post-challenge.</p><p><strong>Results: </strong>Vaccination with both VLPs induced robust RSV-specific IgG and neutralizing antibodies, conferring defense against RSV infection. Compared with the UV-RSV control group, both G_ECD/M2_82-90-VLPs and G_ECD-VLPs groups exhibited significantly increased Th1-type cytokine levels and decreased Th2-type cytokine concentrations (<i>P</i><0.05, <i>P</i><0.001). Importantly, compared to G_ECD-VLPs, G_ECD/M2_82-90-VLPs further significantly upregulated the expression of Th1-type cytokines (IFN-γ, IL-2) and regulatory cytokine IL-10, while significantly downregulating Th2-type cytokine IL-4 (all <i>P</i><0.05). Post-RSV challenge, mice vaccinated with G_ECD/M2_82-90-VLPs exhibited a substantially increased proportion of CD25⁺FoxP3⁺ Treg cells and a decreased percentage of Th17 cells in the lungs. Notably, G_ECD/M2_82-90-VLP vaccination prevented RSV-induced immunopathology.</p><p><strong>Discussion: </strong>Our findings demonstrate that vaccination with G_ECD/M2_82-90-VLPs elicited a balanced immune response and conferred protection against RSV infection without immunopathology. These data demonstrate that the G_ECD/M2_82-90-VLPs are a potential RSV subunit vaccine candidate.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1625670"},"PeriodicalIF":5.9,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of EMT in the immune microenvironment of plasma cell mastitis.","authors":"Meng Zhou, Yubi Zhang, Yuanhao Shao, Bin Wu, Jing Zhou","doi":"10.3389/fimmu.2025.1637725","DOIUrl":"10.3389/fimmu.2025.1637725","url":null,"abstract":"<p><p>Plasma cell mastitis (PCM), a prevalent and refractory form of non-lactating mastitis, is characterized by the pathological triad of ductal ectasia (DE), plasma cell-dominated inflammatory infiltration, and progressive fibrosis. Despite its clinical burden, current surgical interventions yield suboptimal outcomes with recurrence rates up to 43%, underscoring an urgent need for mechanistic insights. This review synthesizes evidence establishing epithelial-mesenchymal transition (EMT) as a central driver of PCM pathogenesis, intricately regulated by the disease-specific immune microenvironment. We demonstrate that autoimmune-mediated DE initiates ductal damage, generating damage-associated molecular patterns (DAMPs) that activate pattern recognition receptors (PRRs). This triggers NF-κB signaling hubs, upregulating pro-inflammatory mediators (IL-1β, IL-6, TGF-β1, ICAM-1, CXCL12) and core EMT-transcription factors (Snail, TWIST). Crucially, IL-6/JAK/STAT3 signaling promotes plasma cell survival via Bcl-2 while concurrently driving EMT in ductal epithelium. Concurrently, IL-1βactivate PI3K/Akt to stabilize EMT effectors and enhance ECM synthesis. A unique, self-amplifying \"EMT-fibrosis loop\" is identified as a PCM hallmark: EMT-derived fibroblasts secrete CXCL12 and TGF-β1, which activate NF-κB pathways in adjacent epithelia to perpetuate EMT and ECM deposition. This loop, alongside sustained plasma cell activity via IL-6/STAT3/Bcl-2, underpins PCM's chronicity and distinguishes it from other mastitides like granulomatous lobular mastitis (GLM). We further highlight exosomal involvement in CXCL12 transport and M1 macrophage polarization as amplifiers of inflammation and EMT. Targeting these convergent pathways (NF-κB, JAK/STAT3) or disrupting the EMT-fibrosis loop (e.g., via CXCL12/TGF-β1 inhibitors) represents a promising therapeutic strategy to mitigate fibrosis and recurrence. Future research must validate these mechanisms in human-relevant models and address critical gaps in bacterial-autoimmune interplay and temporal dynamics across PCM stages.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1637725"},"PeriodicalIF":5.9,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bibliometric analysis of RNA-binding proteins in osteosarcoma: unraveling research trends and hotspots.","authors":"Zhiqian Gu, Songou Zhang, Xudong Hu, Nanjian Xu, Yang Wang, Jian Ruan, Yufeng Qian, Weihu Ma, Hong Chen","doi":"10.3389/fimmu.2025.1577261","DOIUrl":"10.3389/fimmu.2025.1577261","url":null,"abstract":"<p><strong>Background: </strong>RNA-binding proteins (RBPs), a class of molecules that play a crucial role in regulating gene expression, have attracted considerable attention in cancer biology research. RBPs influence osteosarcoma progression by modulating RNA metabolism and participating in cellular proliferation, differentiation, apoptosis, and interactions within the tumor microenvironment. Understanding the current status and future trends of RBPs is crucial for the advancement of osteosarcoma research.</p><p><strong>Methods: </strong>Relevant literature was sourced from the Web of Science, PubMed, and Scopus databases covering the period from January 1, 1994, to December 31, 2024. Using professional analytical tools such as R bibliometrix, VOSviewer, CiteSpace, and SCImago, we conducted a multidimensional visual analysis of publication trends, contributions from countries and institutions, influential authors, significant publications, and keyword distribution.</p><p><strong>Results: </strong>Research on RBPs in osteosarcoma began in 1994, with a notable increase in published studies since 2016. The leading countries for research output were China and the United States, primarily from three major U.S. institutions: the University of Illinois, Harvard University, and UT MD Anderson Cancer Center. Significant contributors to this field included Kannanganattu V. Prasanth, Jean-Yves Masson, Yang Wang. The most cited article was a review titled <i>The potential role of RNA N6-methyladenosine in Cancer progression</i> by Professor Shaoqing Ju from China (2020). Prominent journals within this domain included <i>Cancer Research</i> (USA), <i>Oncogene</i> (England), <i>Cancer Cell International</i> (England), and the <i>Journal of Bone and Mineral Research</i> (USA).</p><p><strong>Conclusion: </strong>This study highlights the critical role of RBPs in osteosarcoma. We conducted a systematic literature review using bibliometric methods to outline the research landscape, identify hotspots and emerging trends, and provide valuable references for future studies. Future research should focus on enhancing international collaboration, exploring molecular mechanisms, and connecting these insights to clinical applications-especially in targeted drug development-to improve treatment outcomes for osteosarcoma patients.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1577261"},"PeriodicalIF":5.9,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monoclonal immunoglobulins on red blood cells: a potential supplementary diagnostic indicator for monoclonal gammopathies.","authors":"Benxia Bing, Xiaowei Yang, Chenghua Wang, Liang Xu, Shiqing Cheng, Yun Liu, Qiuhan Wang, Chunjuan Zhai, Bing Zhao, Rong Wang, Jing Sun","doi":"10.3389/fimmu.2025.1636162","DOIUrl":"10.3389/fimmu.2025.1636162","url":null,"abstract":"<p><strong>Introduction: </strong>Red blood cells (RBCs) have the capability to bind and transport a variety of substances. The aim of this study is to investigate the potential of circulating RBCs as carriers of monoclonal immunoglobulins (M proteins).</p><p><strong>Methods: </strong>Patients who were newly diagnosed with monoclonal gammopathy in the Nephrology Department of Shandong Provincial Hospital affiliated with Shandong First Medical University from April 2023 to December 2024 were included in this study. Western blots were performed on RBC membrane proteins using primary antibodies against human IgG, IgM, IgA, kappa, and lambda.</p><p><strong>Results: </strong>Forty-nine patients with monoclonal gammopathy were enrolled in this study. Substantial increases in the amounts of erythrocyte-bound immunoglobulins, characterized by monoclonal properties, were observed. Among the 49 patients, 45 (91.8%) had M proteins detected on RBCs, 38 (77.6%) had abnormal serum capillary electrophoresis and immunosubtraction (CE/IS) results, 36 (75.3%) had abnormal serum free light-chain (sFLC) ratios, and 32 (65.3%) had abnormal serum total light-chain (sTLC) ratios. 53.1% (26/49) of patients with monoclonal gammopathy had concordant results between erythrocyte Western blot and CE/IS. 22.4% (11/49) of patients had negative serum CE/IS results but extrinsic monoclonal immunoprotein bands on RBCs, which were consistent with the findings from sFLC, bone marrow flow cytometry, or renal histopathology. 16.3% (8/49) of patients had abnormal but inconsistent results between serum CE/IS and erythrocyte electrophoresis. Four (8.2%) patients had no or polyclonal immunoprotein bands on RBCs.</p><p><strong>Conclusion: </strong>Monoclonal immunoglobulins were presented on erythrocytes, which may serve as a supplementary diagnostic indicator for the detection of M proteins.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1636162"},"PeriodicalIF":5.9,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parenteral micronutrient supplementation enhances mammary immune function and colostrum-milk quality by modulating cytokine profiles and oxidative stress in transition crossbred cows.","authors":"Yallappa M Somagond, Pravasini Das, Ajay Kumar Dang, Dhawal K Yadav, Priyanka M Kittur, Bibhudatta S K Panda, Pooja Devi, Aarti Kamboj, Mohanned Naif Alhussien","doi":"10.3389/fimmu.2025.1669246","DOIUrl":"10.3389/fimmu.2025.1669246","url":null,"abstract":"<p><strong>Background: </strong>The transition period in dairy cattle is marked by oxidative stress and immune suppression linked to altered micromineral status. This study evaluated whether parenteral supplementation with trace elements and vitamins could enhance mammary health and improve the immunonutritional quality of colostrum and milk.</p><p><strong>Methods: </strong>Twenty-four multiparous cross-bred cows were blocked by parity and projected yield, then assigned to control, multivitamin (MV; vitamins A, B-complex, D₃, E), multi-mineral (MM; Copper (Cu), Manganese (Mn), Selenium (Se), and Zinc (Zn)), or combined multivitamin and multi-mineral (MMMV) groups. Intramuscular injections were administered on days -30, -15, -7, 0, +7, +15, and +30 relative to calving. Longitudinal sampling was conducted on days 0, 2, 3, 4, 7, 15, and 30 postpartum.</p><p><strong>Results: </strong>MMMV cows produced colostrum and milk with higher fat and protein percentages, stable lactose, and greater concentrations of insulin-like growth factors and immunoglobulins than all other groups (P < 0.05). Mammary health indicators improved concomitantly: somatic cell counts fell, the neutrophil-to-macrophage ratio normalised, and phagocytic activity of both cell types increased. These functional improvements were accompanied by reduced expression of toll-like and chemokine receptors in milk phagocytes. Additionally, the cytokine profile shifted toward an anti-inflammatory state evidenced by lower levels of IL-1β, IL-6, IL-8, IL-17A, and IFN-γ, and higher levels of IL-4 and IL-10. Reduced oxidative stress was indicated by decreased activities of superoxide dismutase, catalase, and glutathione peroxidase in the milk whey of the MMMV group. The MM and MV treatments conferred intermediate benefits, whereas the control group showed the greatest inflammatory and oxidative stress.</p><p><strong>Conclusions: </strong>Repeated parenteral delivery of complementary trace minerals and vitamins throughout the transition period enhances mammary innate immunity, attenuates inflammation and oxidative stress, and augments the nutritive and immunological value of colostrum and milk. This approach offers a practical intervention to safeguard udder health and optimise passive immune transfer to calves.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1669246"},"PeriodicalIF":5.9,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case Report: Relapsing pleural effusions and coated aorta revealing Erdheim-Chester disease.","authors":"Tiépé Rokia Ouattara, Théo Pezel, Gwenael Lorillon, Aïcha Kante, Peggy Reiner, Aurélie Le Gal, Marine Lefèvre, Thibault Vieira, Stéphane Mouly, Abdellatif Tazi, Julien Haroche, Trecy Goncalves, Damien Sène, Jean-François Emile, Cloé Comarmond","doi":"10.3389/fimmu.2025.1585541","DOIUrl":"10.3389/fimmu.2025.1585541","url":null,"abstract":"<p><p>Erdheim-Chester disease (ECD) is a rare histiocytic disorder with localized presentations or multisystem disease. Clinical presentations of ECD are usually non-specific and depends on the site of involvement. ECD can involve one or several organs. Clinical manifestations range from asymptomatic lesions to severe and life-threatening organ dysfunction. Hence, accurate and timely diagnosis is challenging given the rarity and varied presentation of ECD. The most common clinical manifestations are bone pain related to osteosclerosis, usually in the lower limbs. We report here a case with no obvious clinical manifestation of ECD preceding initial recurrent pleural effusions. The diagnosis of ECD was suggested based on pleural thickening revealed by relapsing pleural effusions combined with radiological finding of a coated aorta and slight perirenal infiltrate. Pleural biopsy revealed collagen fibrosis, and immunohistochemistry with the anti-CD163 antibody showed an important infiltration by histiocytes, strong cytoplasmic phosphorylated ERK in the lesional cells, and positive factor XIIIa staining. A cell-free DNA from peripheral blood revealed negative <i>BRAF</i> mutation and the presence of <i>MAP2K1</i> mutation, a key driver mutation in ECD. The diagnosis is often suggested based on clinic-radiological presentation but requiring histopathology to establish a final diagnosis of ECD. Plasma cell-free DNA is a promising and non-invasive tool to detect key driver mutations.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1585541"},"PeriodicalIF":5.9,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The AhR/IL-22 axis in chronic gut inflammation: unraveling mechanisms and therapeutic prospects.","authors":"Huimin Kang, Zheng Chen, Baodong Wang, Zhiyun Chen","doi":"10.3389/fimmu.2025.1668173","DOIUrl":"10.3389/fimmu.2025.1668173","url":null,"abstract":"<p><p>Chronic inflammatory bowel diseases, including Crohn's disease (CD), ulcerative colitis (UC), and post-infectious irritable bowel syndrome (PI-IBS), are characterized by immune-mediated intestinal inflammation and epithelial barrier dysfunction. Research indicates that the aryl hydrocarbon receptor (AhR)/interleukin-22 (IL-22) pathway is critical for intestinal homeostasis. This pathway can be activated by ligands from dietary and microbial sources (such as tryptophan metabolites), and AhR signaling in immune cells (particularly type 3 innate lymphoid cells (ILC3s) and T cells) is the primary driver of IL-22 production. IL-22 protects the intestinal barrier and regulates inflammatory responses by promoting epithelial repair, enhancing mucus and antimicrobial defenses, and strengthening tight junctions. Dysregulation of this pathway plays a key role in the pathogenesis of chronic intestinal inflammation, leading to exacerbated inflammatory processes and mucosal damage. Given its central role in barrier defense and repair, targeting the AhR/IL-22 pathway has emerged as a novel therapeutic direction for restoring intestinal homeostasis. This review summarizes the mechanisms of action of this pathway in chronic intestinal inflammation and explores its potential as a novel therapeutic target.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1668173"},"PeriodicalIF":5.9,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunization route-mediated differences in long-term maturation of humoral immune response induced by adenovirus vector-based COVID-19 vaccine Sputnik V in nonhuman primates.","authors":"Amir I Tukhvatulin, Ilya V Gordeychuk, Alina S Dzharullaeva, Inna V Dolzhikova, Ekaterina O Bayurova, Fatima M Izhaeva, Anna V Kovyrshina, Alla S Zhitkevich, Daria V Avdoshina, Stanislav A Gulyaev, Tatiana V Gulyaeva, Andrey V Moroz, Ilias B Esmagambetov, Ilya D Zorkov, Anna A Iliukhina, Artem Y Shelkov, Alina S Erokhova, Dmitry V Shcheblyakov, Olga V Zubkova, Aydar A Ishmukhametov, Denis Y Logunov, Alexander L Gintsburg","doi":"10.3389/fimmu.2025.1634187","DOIUrl":"10.3389/fimmu.2025.1634187","url":null,"abstract":"<p><strong>Introduction: </strong>On the background of kaleidoscopic changes of SARS-CoV-2 circulating variants, constant presence of SARS-CoV-2 in the human population hampers the dissection of native long-term immunogenicity of COVID-19 vaccines.</p><p><strong>Methods: </strong>For this purpose, we performed a more than two-year-long evaluation of parameters of the humoral immune response elicited by intramuscularly (IM) and intranasally (IN) delivered adenovirus vector-based Sputnik V vaccine in nonhuman primates (NHP, Common marmosets), which are naturally nonsusceptible for SARS-CoV-2 infection.</p><p><strong>Results: </strong>Although both immunization routes elicited prominent humoral immune responses in a short-term perspective, the long-term kinetics significantly differed between the IM and IN groups. While the titers of local and systemic antigen-specific antibodies (both IgA and IgG) nearly disappeared within two years upon IN vaccination, IM vaccination led to the highest IgG values in nasal swabs as well as IgA and IgG in serum specimens from NHPs by the end of observation period (day 764). Unlike IN vaccination, IM vaccination also resulted in a continuous long-term increase in serum maturation parameters such as antibody avidity, neutralization potency and breadth.</p><p><strong>Discussion: </strong>The present study provides valuable information about distinct features of the long-term postvaccination humoral immune response in nonhuman primates induced by adenoviral COVID-19 vaccine administered by the intramuscular and intranasal routes commonly used in clinical practice.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1634187"},"PeriodicalIF":5.9,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12464043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}