Lin Zhang, Jing Yu, Bowen Deng, Yi Peng, Yafang Shao, Jinsong Bao
{"title":"Genotypic Variation and Genetic Control of Phenolic Compounds and Antioxidant Activity in Shanlan Upland Rice Landrace.","authors":"Lin Zhang, Jing Yu, Bowen Deng, Yi Peng, Yafang Shao, Jinsong Bao","doi":"10.3390/ijms26199800","DOIUrl":"10.3390/ijms26199800","url":null,"abstract":"<p><p>Shanlan rice, a unique drought-resistant rice germplasm resource in Hainan Province, China, holds significant potential for rice genetic improvement and breeding innovation. However, its genetic diversity and significance in rice breeding remain inadequately explored. This study conducted a comprehensive analysis of phenolic acid profiles and antioxidant properties in the brown rice of 84 Shanlan rice accessions. It was revealed that colored Shanlan rice accessions exhibited significantly higher total phenolic content (249.00-2408.33 mg gallic acid equivalents per 100 g of rice flour (mg GAE/100 g)) and antioxidant capacity (DPPH: 680.39-809.63 micromoles of Trolox equivalent per 100 g (μmol TE/100 g); ABTS: 529.93-1917.77 μmol TE/100 g) compared to white-grained varieties. High-performance liquid chromatography (HPLC) analysis identified eight phenolic acids in the bound fractions, among which the sinapic acid (55.08 μg/g) and vanillic acid (11.72 μg/g) were predominant, accounting for over 60% of total bound phenolic acid content. A genome-wide association study (GWAS) identified 84 significant loci associated with these phenolic-related traits. A major quantitative trait locus (QTL) on chromosome 7 for free phenolic content, total phenolic content, flavonoids, and DPPH activity was co-located at the <i>Rc</i> gene locus, a key regulator of red pericarp pigmentation and proanthocyanidin biosynthesis. Haplotype analysis identified ten haplotypes in <i>Rc</i>, with the haplotype H002 showing the highest antioxidant capacity. Another QTL on chromosome 11 was associated with p-coumaric, vanillic, and sinapic acids, although no significant difference was observed in haplotype analysis. These results highlight <i>Rc</i> as a key genetic factor underlying antioxidant properties in rice, while other loci require further validation. This research provides a foundation for breeding health-benefit, drought-tolerant rice cultivars using Hainan's unique germplasm.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zuo Hu, Zhihao Zhu, Hisaya K Ono, Shouhei Hirose, Yukiko Hara-Kudo, Shaowen Li, Dong-Liang Hu
{"title":"Effects of Nutritional Conditions on Growth, Biofilm Formation, and Enterotoxin Production in <i>Staphylococcus aureus</i> Associated with Food Poisoning.","authors":"Zuo Hu, Zhihao Zhu, Hisaya K Ono, Shouhei Hirose, Yukiko Hara-Kudo, Shaowen Li, Dong-Liang Hu","doi":"10.3390/ijms26199791","DOIUrl":"10.3390/ijms26199791","url":null,"abstract":"<p><p>Staphylococcal food poisoning (SFP) is a common foodborne illness caused by the ingestion of enterotoxins produced by <i>Staphylococcus aureus</i>, posing a persistent global public health concern. Although regional differences in implicated food types and predominant enterotoxins have been reported, the underlying factors remain unclear. In this study, we systematically investigated the effects of nutritional factors on the growth, biofilm formation, and production of two representative enterotoxins, SEA and SEB, by <i>S. aureus</i>. Specifically, we evaluated bacterial responses to different concentrations of NaCl, glucose, and tryptone. NaCl suppressed growth, biofilm formation and enterotoxin production in a dose-dependent manner. Glucose markedly inhibited both bacteria growth and enterotoxin production, with a stronger effect on SEB than SEA. In contrast, tryptone promoted bacterial growth and moderately enhanced biofilm formation but did not significantly affect enterotoxin production. Importantly, even under comparable bacterial counts, the types and amounts of SEs produced varied substantially depending on the nutrient composition. These findings provide new insights into the nutrient-dependent regulation of virulence in <i>S. aureus</i> and highlight the importance of considering environmental and nutritional factors when assessing risks of SFP and designing effective food safety strategies.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gaetano Pacinella, Mariarita Margherita Bona, Federica Todaro, Anna Maria Ciaccio, Mario Daidone, Antonino Tuttolomondo
{"title":"Tracing Inflammation in Ischemic Stroke: Biomarkers and Clinical Insight.","authors":"Gaetano Pacinella, Mariarita Margherita Bona, Federica Todaro, Anna Maria Ciaccio, Mario Daidone, Antonino Tuttolomondo","doi":"10.3390/ijms26199801","DOIUrl":"10.3390/ijms26199801","url":null,"abstract":"<p><p>Ischemic stroke is now widely recognized as a disease with a strong inflammatory profile. Cerebral vascular damage is both preceded and followed by a chain of molecular events involving immune cells and inflammatory markers, irrespective of the etiology of the ischemic injury. Over time, an increasingly comprehensive understanding of these markers has led to a better insight into the mechanisms behind the vascular event and recovery following ischemic stroke. However, to date, there are still no available circulating or tissue biomarkers for early diagnosis or prognostic stratification, making ischemic stroke diagnosis contingent on clinical and instrumental investigations. However, neurological and internal medicine research is progressing in identifying markers that could potentially take on this role. This manuscript, therefore, aims to review the most recent and innovative results of medical advances, summarising the current state of the art and future perspectives. If ischaemic stroke is an inflammatory disease, it is also true that it is not just a singular condition, but a group of entities with their own neuroinflammatory features. Thus, given that, in ischemic cerebral vascular damage, \"time is brain,\" tracking increasingly accurate markers in the diagnosis of ischemic stroke is a valuable tool that will potentially enable earlier recognition of this disease and, hopefully, make it less disabling and more widely treated.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comparative Proteomics, Functional Characterization and Immunological Cross-Reactivity Studies on Russell's Viper Venom from Two Distinct Geographical Regions in South India.","authors":"Nisha Reghu, Sudharshan Rao, Dileepkumar Raveendran, Bipin Gopalakrishnan Nair, Muralidharan Vanuopadath","doi":"10.3390/ijms26199734","DOIUrl":"10.3390/ijms26199734","url":null,"abstract":"<p><p>Snakebite envenoming is a neglected tropical disease contributing to a significant number of morbidities and mortalities globally. Reports indicate that venom variation influences antivenom efficacy, which might affect treatment outcomes. The venom composition of <i>Daboia russelii</i> (Russell's viper), one of the big four snakes in India, has been extensively studied from different geographical regions of India. Nonetheless, the Russell's viper venom proteome from Kerala (Western Ghats region), together with its study in comparison with the same species' venom from Tamil Nadu, has not been explored yet. In the current study, <i>Daboia russelii</i> venom from Irula (RVi) and the Western Ghats region in Kerala (RVwg) was characterized through mass spectrometry-based proteomics and few functional assays. The proteomics study identified 52 proteins from 14 snake protein families in RVi and 61 proteins from 17 snake venom protein families in RVwg. Some of the protein families, including DNase and hyaluronidase, as well as vascular endothelial growth factor, were exclusively identified in RVwg venom. Comparative functional analysis indicated that RVwg exhibited higher fibrinogenolytic and hyaluronidase activities, while RVi venom showed higher phospholipase A<sub>2</sub> and L-amino acid oxidase activities. Through ELISA, RVi venom showed an end-point titration value of 1:24,300 for all the antivenoms used in this study, whereas for RVwg, compared to PSAV (Premium serums and vaccines) (1:2700), Virchow and VINS (both 1:8100) antivenoms showed better immunological cross-reactivity. Immunoblotting experiments indicated differential binding and recognition of antigenic epitopes present in both venoms by the polyvalent antivenoms used in the current study. All these findings highlight that the venom proteome varies according to the geographical location, and this significantly influences antivenom efficacy.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Crosstalk Between Allergic Inflammation and Autophagy.","authors":"Jaewhoon Jeoung, Wonho Kim, Dooil Jeoung","doi":"10.3390/ijms26199765","DOIUrl":"10.3390/ijms26199765","url":null,"abstract":"<p><p>Autophagy is a conserved process that involves the degradation of damaged proteins and organelles to restore cellular homeostasis. Autophagy plays a critical role in cell differentiation, immune responses, and protection against pathogens, as well as the development and progression of allergic inflammation. Crosstalk between autophagy and signaling pathways modulates immune responses to inflammatory signals. Here, we discuss the regulatory roles of autophagy in allergic inflammation. Autophagy can promote allergic inflammation by enhancing the secretion of inflammatory mediators. Impaired autophagy resulting from the accumulation of autophagosomes can exacerbate allergic inflammation. Mast cell degranulation and activation require energy provided by mitochondrial respiration. Mast cell activation is accompanied by morphological changes and mitochondrial fragmentation. Mitochondrial fragmentation (mitophagy) induced by oxidative stress involves the degradation of defective mitochondria. Therefore, we discuss the relationship between mitophagy and allergic inflammation. Targeting autophagy and oxidative stress can be a strategy for developing anti-allergy therapeutics. In this review, we also discuss future research directions to better understand allergic diseases with respect to autophagy and develop effective anti-allergy drugs.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seung-Kyo Jeong, Jae-Ryoung Park, Eun-Gyeong Kim, Kyung-Min Kim
{"title":"Development of Resistance to Damping-Off in Rice, <i>Oryza sativa</i> L., Using CRISPR/Cas9.","authors":"Seung-Kyo Jeong, Jae-Ryoung Park, Eun-Gyeong Kim, Kyung-Min Kim","doi":"10.3390/ijms26199761","DOIUrl":"10.3390/ijms26199761","url":null,"abstract":"<p><p>Damping-off disease hinders rice seedling growth and reduces yield. Current control methods, such as seed or soil sterilization, rely on chemicals that cause environmental pollution and promote pathogen resistance. As a sustainable alternative, we targeted the damping-off resistance-related gene <i>OsDGTq1</i> using CRISPR/Cas9. Field experiments first verified <i>OsDGTq1</i>'s significance in resistance. The CRISPR/Cas9 system, delivered via Agrobacterium-mediated transformation, was used to edit <i>OsDGTq1</i> in rice cultivar Ilmi. Lesions from major damping-off pathogens, <i>Rhizoctonia solani</i> and <i>Pythium graminicola</i>, were observed on G<sub>0</sub> plants. All 37 regenerated plants contained T-DNA insertions. Among them, edits generated by sgRNA1-1, sgRNA1-2, and sgRNA1-3 resulted in the insertion of two thymine bases as target mutations. Edited lines were assigned names and evaluated for agronomic traits, seed-setting rates, and pathogen responses. Several lines with edited target genes showed distinct disease responses and altered gene expression compared to Ilmi, likely due to CRISPR/Cas9-induced sequence changes. Further studies in subsequent generations are needed to confirm the stability of these edits and their association with resistance. These results confirm that genome editing of <i>OsDGTq1</i> alters resistance to damping-off. The approach demonstrates that gene-editing technology can accelerate rice breeding, offering an environmentally friendly strategy to develop resistant varieties. Such varieties can reduce chemical inputs, prevent pollution, and minimize seedling loss, ultimately enhancing food self-sufficiency and stabilizing rice supply.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Haoyang Yu, Xia Niu, Bingyu Niu, Peng Lei, Ning Xu, Sitong Yang, Quanyong Yu, Guiling Li, Lulu Wang
{"title":"Liver-Targeted Scutellarin Nanoemulsion Alleviates Fibrosis with Ancillary Modulation of the Gut-Liver Microbiota.","authors":"Haoyang Yu, Xia Niu, Bingyu Niu, Peng Lei, Ning Xu, Sitong Yang, Quanyong Yu, Guiling Li, Lulu Wang","doi":"10.3390/ijms26199746","DOIUrl":"10.3390/ijms26199746","url":null,"abstract":"<p><p>Liver fibrosis, a progressive condition with limited pharmacotherapies, poses a global health challenge. Scutellarin (SCU), a flavonoid derived from <i>Erigeron breviscapus</i>, has demonstrated anti-fibrotic activity and modulates gut microbiota. Emerging evidence suggests that SCU may also influence the hepatic microbiome. However, its clinical utility is constrained by poor water solubility and low oral bioavailability. Here, we developed an SCU-loaded nanoemulsion (SCE) to enhance solubility and liver-targeted delivery. In vitro, SCE increased SCU uptake in hepatic stellate cells (HSCs) and significantly inhibited TGF-β1-induced fibrogenesis. In a bile duct ligation (BDL) mouse model, oral administration of SCE improved hepatic SCU accumulation and produced superior anti-fibrotic efficacy. SCE treatment attenuated fibrosis and collagen deposition in the liver and improved liver function markers. Mechanistic investigations using 16S rRNA sequencing revealed that SCU treatment was associated with beneficial microbiota changes, although its main therapeutic effects were achieved through enhanced hepatic targeting. Notably, the SCE formulation was well-tolerated, showing no significant toxicity in vitro or in vivo. In conclusion, the SCU-loaded nanoemulsion achieved enhanced hepatic delivery of SCU and exerted potent anti-fibrotic effects via multiple mechanisms, including direct suppression of fibrogenesis and ancillary modulation of the gut-liver microbiome, offering a promising therapeutic strategy for liver fibrosis.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Massimiliano Cordaro, Giulia Neri, Shoeb Anwar Mohammed Khawja Ansari, Rocco Buccheri, Angela Scala, Anna Piperno
{"title":"Synthesis and Biological Profile of Omaveloxolone: The Cornerstone for Friedreich Ataxia Treatment.","authors":"Massimiliano Cordaro, Giulia Neri, Shoeb Anwar Mohammed Khawja Ansari, Rocco Buccheri, Angela Scala, Anna Piperno","doi":"10.3390/ijms26199747","DOIUrl":"10.3390/ijms26199747","url":null,"abstract":"<p><p>This review provides a comprehensive overview of the therapeutic potential of omaveloxone (OMA) for the treatment of Friedreich's ataxia (FA), along with an analysis of the historical development and current status of the synthetic strategies for OMA production. OMA activates the nuclear factor-2-(erythroid-2)-related (Nrf2) pathway in vitro and in vivo, in both animal models and humans. The Nrf2 pathway plays a crucial role in the cellular response to oxidative stress. Furthermore, OMA has been shown to mitigate mitochondrial dysfunction, restore redox homeostasis and downregulate nuclear factor-κB (NF-κB), a key mediator of inflammatory responses. Through these mechanisms, OMA contributes to tissue protection and inflammation reduction in patients with FA. The review also highlights future perspective, focusing on the challenges associated with OMA reprofiling through innovative drug delivery approaches and its potential repurposing for diseases beyond FA.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daria M Yurkina, Elena A Romanova, Aleksandr S Chernov, Irina S Gogleva, Anna V Tvorogova, Alexey V Feoktistov, Rustam H Ziganshin, Denis V Yashin, Lidia P Sashchenko
{"title":"Hsp70 Peptides Induce TREM-1-Dependent and TREM-1-Independent Activation of Cytotoxic Lymphocytes.","authors":"Daria M Yurkina, Elena A Romanova, Aleksandr S Chernov, Irina S Gogleva, Anna V Tvorogova, Alexey V Feoktistov, Rustam H Ziganshin, Denis V Yashin, Lidia P Sashchenko","doi":"10.3390/ijms26199750","DOIUrl":"10.3390/ijms26199750","url":null,"abstract":"<p><p>The novel data show that the Hsp70 protein is a potent activator of the immune system. Using limited trypsinolisis, we have identified the epitopes of Hsp70 responsible for TREM-1-dependent and TREM-1-independent cytotoxicity. The 11aa N9 peptide (AMTKDNNLLGR) contains nine amino acids that correspond to the amino acid sequence of the known TKD peptide. Also, like TKD, this peptide does not interact with the TREM-1 receptor but activates CD94+ NK cells that kill tumor cells by secreting granzymes and inducing apoptosis. The 16aa peptide N7 (SDNQPGVLIQVYEGEK) interacts with the TREM-1 receptor and induces the activation of NK cells and cytotoxic T lymphocytes at different time points. T-lymphocytes activated by this peptide induce two alternative processes of cell death in HLA-negative tumor cells, apoptosis and necroptosis, through the interaction of the FasL lymphocyte with the Fas receptor of the tumor cell. A shortened fragment of this peptide, N7.1 (SDNQPGVL), has been identified that inhibits the interaction of TREM-1 with its ligands. This peptide has shown protective effects in the development of sepsis in mice. The results obtained can be used in antitumor and anti-inflammation therapy.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jaisel A Cervantes, T Paul Welch, Brian Kaiser, Charles A Bill, Angel Torres, Gareth L Bill, Colin A Bill, Charlotte M Vines
{"title":"Signaling via C-C Chemokine Ligand 19 and Extracellular Regulated Kinase 5 in T Cells Limits the Humoral Adaptive Immune Response in Mice.","authors":"Jaisel A Cervantes, T Paul Welch, Brian Kaiser, Charles A Bill, Angel Torres, Gareth L Bill, Colin A Bill, Charlotte M Vines","doi":"10.3390/ijms26199744","DOIUrl":"10.3390/ijms26199744","url":null,"abstract":"<p><p>Misregulation of C-C chemokine receptor 7 (CCR7) has been linked to multiple autoimmune diseases including systemic lupus erythematosus, multiple sclerosis, and ankylosing spondylitis. As a G-protein-coupled receptor, located on the cell membrane, CCR7 can be targeted by inhibiting one of its two ligands, C-C chemokine ligand 19 (CCL19), to regulate its function. In this study, we examined signaling events downstream of CCL19 binding that provide a mechanism for regulation of the immune response. We used a CCR7 antagonist, CCL19<sub>8-83</sub>, in immune studies in vivo, as a platform for a pharmaceutical to define the molecular events that are involved in regulating the humoral adaptive immune response. We found that in the presence of a T-cell-dependent antigen, C57BL/6 mice treated during antigen exposure with CCL19<sub>8-83</sub> generated significantly higher levels of IgG1, the dominant isotype in extracellular bacterial infections that can activate complement, and IgG2c, the dominant isotype during viral and intracellular bacterial infections. Inhibiting ERK5 signaling downstream of CCR7 activation by CCL19, or disruption of CCL19 expression in CCL19<sup>-/-</sup> mice, also resulted in higher levels of IgG1 when compared to control mice. Differences in levels of IL-4 or other cytokines or lymphocyte types between wild-type and ERK5-deficient T cells did not account for antibody levels. Since pertussis-toxin-induced inhibition of lymphocyte chemotaxis is linked to elevated levels of IgG, we examined the effect of ERK5 on chemotaxis to CCR7 ligand CCL19. We found that disruption of ERK5 in T cells, or global disruption of CCL19 or CCR7, inhibited chemotaxis of T cells to CCL19, a mechanism that enhances sensitization during the exposure to an immunogen. Since CCR7 and its ligands have been linked to autoimmunity, these studies may provide insight into mechanisms that can be targeted to control autoimmune responses.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}