Molecular immunology最新文献

{"title":"Increased TNF-α in SJS/TEN induced by PD-1 inhibitors supports the combination therapy of etanercept and systemic corticosteroids","authors":"Hao Xiong,&nbsp;Zhu Shen","doi":"10.1016/j.molimm.2025.12.006","DOIUrl":"10.1016/j.molimm.2025.12.006","url":null,"abstract":"<div><h3>Background</h3><div>Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis (SJS/TEN) induced by programmed cell death protein 1 (PD-1) inhibitors is a life-threatening condition. Although the exact pathogenesis remains unknown, its treatment mainly relies on high-dose systemic corticosteroids. Given the vital role of tumor necrosis factor-alpha (TNF-α) in classic SJS/TEN, this study sought to investigate the expression of TNF-α and evaluate the effectiveness and safety of combination therapy of etanercept and systemic corticosteroids in PD-1 inhibitor-induced SJS/TEN.</div></div><div><h3>Methods</h3><div>PD-1 inhibitor-induced SJS/TEN patients (n = 5) meeting diagnostic criteria, including skin biopsy-confirmed full-thickness epidermal necrosis with PD-1 as the sole culprit drug by ALDEN scoring, were enrolled in the study. Single-cell RNA sequencing (scRNA-seq) was conducted on lesional skin from one index patient (blister, erythema, and normal sites). Immunofluorescence staining for TNF-α was performed on samples from all five patients. Finally, a combination therapy of etanercept and systemic corticosteroids was administered to the patients, and the re-epithelization time, corticosteroid treatment duration, and prednisone cumulative dose were analyzed.</div></div><div><h3>Results</h3><div>scRNA-seq revealed significantly increased TNF-α expression in lesional skin compared with normal skin (<em>p</em> &lt; 0.05), primarily from macrophages, which represented the predominant cell population in the lesion. Immunofluorescence confirmed TNF-α elevation in all five patients (<em>p</em> &lt; 0.05). Besides, combination therapy resulted in rapid re-epithelialization (5.75 ± 1.48 days), a shorter steroid duration (17.75 ± 2.86 days), and reduced cumulative prednisone use (9.83 ± 3.71 mg/kg). No treatment-related severe adverse events occurred. One patient subsequently received a PD-1 inhibitor after recovery and tolerated the re-treatment without complication.</div></div><div><h3>Conclusions</h3><div>Our findings demonstrated upregulation of TNF-α expression in PD-1 inhibitor-induced SJS/TEN, mainly derived from macrophages. The combination of etanercept and systemic corticosteroids exhibits huge potential for treating this patient population.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 174-180"},"PeriodicalIF":3.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145787083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxic conditioning induced by CoCl2 enhanced the therapeutic effects of mesenchymal stem cell-derived exosomes on oxazolone-induced atopic dermatitis-like skin lesions in BALB/c mice","authors":"Jin-Woo Kim ,&nbsp;Hyeon Ji Lee ,&nbsp;Pahn-Shick Chang ,&nbsp;Jung Min Lee ,&nbsp;Jin-Chul Kim","doi":"10.1016/j.molimm.2025.12.008","DOIUrl":"10.1016/j.molimm.2025.12.008","url":null,"abstract":"<div><div>Atopic dermatitis (AD) is a chronic skin disease characterized by inflammation and disruption of the skin barrier. It is normally treated using moisturizers and steroids; however, these are palliatives and do not serve as a therapy. Mesenchymal stem cells (MSCs) are tissue stem cells with immunomodulatory activities, and exosomes reflect the physiologies of producer cells. Therefore, the use of MSCs and exosomes with their immunomodulatory activities is emerging as a new method to treat AD. Here, we used cobalt chloride (CoCl₂) to induce hypoxic conditioning, and tested the therapeutic efficacy of exosomes derived from CoCl₂-treated MSCs in treating AD. <em>In vitro</em>, the exosomes derived from CoCl₂-treated MSCs increased the proliferation of HaCaT cells and decreased inflammatory cytokine levels. In the oxazolone-induced chronic AD mouse model, the exosomes derived from CoCl₂-treated MSCs reduced ear thickness, restored the skin barrier, and reduced immune cell infiltration and inflammatory markers. These data indicated that hypoxic conditioning induced by the CoCl₂ treatment enhanced the therapeutic efficacy of exosomes derived from MSCs, suggesting that these exosomes can be used to alleviate the symptoms of AD. Given the current AD treatment landscape dominated by biologics and JAK inhibitors, our approach may serve as a steroid-sparing, biologic-agnostic adjunct or alternative, leveraging the safety and manufacturability of cell-free therapy.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 153-162"},"PeriodicalIF":3.0,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145781462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of miR-3188-mediated transcriptional activation of IL-7Rα in tumor immunotherapy research","authors":"Dan Wan ,&nbsp;Xiao Liang ,&nbsp;Fanfan Liang ,&nbsp;Mengchen Zhu ,&nbsp;Chongyu Zhang ,&nbsp;Shaoying Zhang","doi":"10.1016/j.molimm.2025.12.007","DOIUrl":"10.1016/j.molimm.2025.12.007","url":null,"abstract":"<div><h3>Background</h3><div>Adoptive cell therapy (ACT) utilizing tumor-infiltrating lymphocytes (TIL) is a promising immunotherapeutic approach for disseminated malignancies. However, <em>ex vivo</em>-expanded tumor-infiltrating lymphocytes (TIL) often rapidly progress to a state of functional exhaustion or suppression within the tumor microenvironment. Interleukin-7(IL-7) not only supports the survival of T-lymphocyte <em>in vivo</em> but also induces vigorous expansion of naïve and memory T lymphocytes <em>in vitro</em>. Upregulating the expression of interleukin-7 receptor alpha (<em>IL-7Rα</em>) helps T cells restore their responsiveness to <em>IL-7</em> signaling, aids in their survival, and enables them to regain anti-tumor activity.</div></div><div><h3>Methods</h3><div>Firstly, we utilized databases to analyze the expression changes of <em>CD127</em> in different tumor tissues, clarifying the correlation between its expression changes and patient prognosis. Subsequently, we collected clinical patient samples to validate the expression changes of <em>CD127</em> in tumor-infiltrating T cells. We also simulated the tumor microenvironment through <em>in vitro</em> co-culture to explore the impact of tumor cells on the expression of <em>CD127</em> on the surface of T cells. After then, we screened for miRNAs that are complementary to the sequence of the TATA box region in the <em>CD127</em> promoter and employed a <em>CD127</em> promoter driven dual-luciferase reporter system to identify the specific miRNA capable of upregulating <em>CD127</em> expression. Finally, we analyzed the effects of miRNA-mediated upregulation of <em>CD127</em> on T cell function.</div></div><div><h3>Results</h3><div>Bioinformatics analysis and clinical validation both confirmed decreased <em>IL-7Rα</em> expression in tumors. Moreover, in clinical samples, <em>IL-7Rα</em> and <em>miR-3188</em> expression levels showed concordant changes and a positive correlation. <em>miR-3188</em> can upregulate the expression level of <em>IL-7Rα</em> by specifically targeting the TATA-box region of <em>CD127</em> promoter. Utilizing <em>miR-3188</em> to upregulate <em>IL-7Rα</em> expression can facilitate T cell survival, promote the development of memory T cells and enhance the secondary response and tumor-killing capacity of T cells.</div></div><div><h3>Conclusion</h3><div>Our findings reveal a novel mechanism of <em>IL-7Rα</em> regulation and propose a potential strategy to improve the persistence and functionality of T cells for ACT.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 142-152"},"PeriodicalIF":3.0,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145775059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction of Enterococcus faecium-mediated ExoU vaccine and its protective effect in mice challenged with Pseudomonas aeruginosa","authors":"Fan Yang ,&nbsp;Shuhan Yang ,&nbsp;Xingkun Ou ,&nbsp;Ailin He ,&nbsp;Xuhong Yang ,&nbsp;Wengui Li","doi":"10.1016/j.molimm.2025.11.007","DOIUrl":"10.1016/j.molimm.2025.11.007","url":null,"abstract":"<div><h3>Background</h3><div><em>Pseudomonas aeruginosa</em> (Pa) is an opportunistic pathogen and an important cause of nosocomial infections, and its antimicrobial resistance is a major therapeutic challenge. DNA vaccination is an attractive antigen-specific immunotherapy approach.</div></div><div><h3>Methods</h3><div>In this study, we used the most acutely cytotoxic effector exoenzyme U (ExoU) released by Pa as the specific antigen and the safe and reliable <em>Enterococcus faecium</em> (Ef) as the expression vector, to construct the recombinant Ef-ExoU vaccine. The immune protection and humoral and cellular immune responses of the DNA vaccine were evaluated in mice by oral gavage.</div></div><div><h3>Results</h3><div>We found that the Ef-ExoU vaccine significantly reduced lung bacterial load and lung inflammatory cytokines (IL-6, TNF-α), probably by inducing higher levels of IgG and spleen CD4⁺ T cell proliferation, indicating the induction of a mixed Th1 and Th2 immune response.</div></div><div><h3>Conclusions</h3><div>This study suggests that Ef-ExoU is a promising subunit vaccine candidate and provides a new strategy for the prevention and treatment of Pa infection.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 133-141"},"PeriodicalIF":3.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145734390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunological pathways triggered by Porphyromonas gingivalis in periodontitis: New insights into molecular mechanisms","authors":"Klara Ferenc ,&nbsp;Anna Bożek ,&nbsp;Katarzyna Gawron","doi":"10.1016/j.molimm.2025.12.001","DOIUrl":"10.1016/j.molimm.2025.12.001","url":null,"abstract":"<div><div>Periodontitis (PD) is one of the most common chronic inflammatory diseases worldwide. One of the keystone causative agents of PD is considered an anaerobic, Gram-negative, opportunistic oral bacterium - <em>Porphyromonas gingivalis</em>, which has evolved sophisticated mechanisms to evade host immune responses, thus contributing to persistent inflammation and periodontal tissue destruction. As reported in the literature, <em>P. gingivalis</em> interacts with various host receptors and manipulates key immunological signaling pathways, including Toll-like receptor (TLR) signaling, the complement system, and PI3K-AKT signaling. By disrupting these pathways, it subverts host defense mechanisms, promotes dysbiosis, and exacerbates PD progression. Furthermore, emerging evidence suggests, that <em>P. gingivalis</em> infections may have systemic implications, linking PD to conditions, such as, neurodegenerative disorders, rheumatoid arthritis, and cardiovascular diseases. We discussed in this review the molecular mechanisms by which <em>P. gingivalis</em> manipulates key signaling pathways of inflammation and provided a comprehensive review of the intricate molecular interactions between <em>P. gingivalis</em> and host immune responses, emphasizing the ability of this oral pathogen to alter fundamental signaling cascades. Continued exploration of the molecular interplay between this pathogen and the host immune system will not only enhance our knowledge of PD but may also have broader implications for understanding pathogenetic events of associated systemic inflammatory conditions.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 119-132"},"PeriodicalIF":3.0,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria in pyroptosis: Mechanisms and implications","authors":"Basmah M. Eldakhakhny ,&nbsp;Wesam h. Abdulaal ,&nbsp;Johra Khan ,&nbsp;Amir Ajoolabady ,&nbsp;Domenico Pratico ,&nbsp;Suhad Bahijri ,&nbsp;Jaakko Tuomilehto ,&nbsp;Anwar Borai ,&nbsp;Bonglee Kim ,&nbsp;Jun Ren","doi":"10.1016/j.molimm.2025.12.002","DOIUrl":"10.1016/j.molimm.2025.12.002","url":null,"abstract":"<div><div>Pyroptosis is an inflammatory, necrotic, and lytic form of programmed cell death, involving activation of inflammasome complexes, inflammatory caspases, and the cleavage of gasdermins. Gasdermins are a large family of pore-forming proteins with critical implications in key cellular processes and inflammatory disease contexts. These gasdermins subsequently oligomerize to form pores in the plasma membrane, releasing cellular contents and inflammatory mediators. Mechanistically, pyroptosis can occur via either caspase-1-dependent canonical pathway or the caspase-1-independent non-canonical pathway, both ultimately resulting in similar forms of pyroptotic cell death. While the underlying mechanisms of pyroptosis are broad and complex, certain key processes simplify the understanding of these mechanisms. One such critical process is the role of mitochondria and mitochondrial dysfunction in mediating pre-pyroptotic signaling. This review aims to provide a brief overview of the general mechanisms of pyroptosis, followed by a discussion of the latest findings on the functional and regulatory roles of mitochondria in pyroptosis. Moreover, we aimed to discuss and decipher emerging concepts such as the interaction between gasdermin D and cardiolipin, the role of mitochondrial DNA and its associated signaling pathways, as well as perspectives on the clinical relevance of these findings in conditions like sepsis, cardiotoxicity, and other diseases.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 98-105"},"PeriodicalIF":3.0,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145678169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of GNB2L1 promotes expansion of CD74+ dendritic cells and contributes to development of diabetic foot ulcers","authors":"Yuan Wang ,&nbsp;Bing Hang ,&nbsp;Hongshan Liu,&nbsp;Chuantao Cheng","doi":"10.1016/j.molimm.2025.12.003","DOIUrl":"10.1016/j.molimm.2025.12.003","url":null,"abstract":"<div><div>Refractory diabetic foot ulcers (DFUs) are characterized by low-grade chronic inflammation both locally and systemically. GNB2L1 has been reported to be associated with wound healing in diabetic rats, but the specific mechanism by which it acts has not been explored. scRNA-seq data from foot skin samples of three diabetic patients without DFU (non-DFU) and four diabetic patients with non-healing DFU (DFU) were downloaded from the GSE165816 dataset and analyzed. Twenty-five different cell clusters and fourteen cell types were identified, and the dendritic cell (DC) cluster was identified as a meaningful cell type. Skin wound tissues from 36 patients with DFU and 30 diabetic patients without DFU were collected. Based on gene signature analysis of the DC cluster, we identified a CD74⁺ DC subset with a high proportion in the DFU group in clinical samples. Moreover, enrichment analysis of differentially expressed genes in the DC cluster revealed that they were mainly related to infection, immune response, and ATP synthesis. GNB2L1 was identified as the most significantly down-regulated gene, and its expression level was negatively correlated with the wound healing time in DFU patients. A full-thickness dorsal wound model in db/db mice was established, and GNB2L1 upregulation promoted wound healing in db/db mice. CD74⁺ and CD74^- DCs were isolated from blood samples of the above patients. CD74 upregulation promoted mitochondrial damage in DCs, which was reversed by GNB2L1 overexpression. In conclusion, GNB2L1 deficiency promotes CD74⁺ dendritic cell expansion and diabetic foot ulcer development.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 106-118"},"PeriodicalIF":3.0,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145678213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Verticinone inhibits cell growth and induces pyroptosis via regulating AKT pathway in papillary thyroid cancer","authors":"Xincheng Liu,&nbsp;Yang Liu","doi":"10.1016/j.molimm.2025.11.014","DOIUrl":"10.1016/j.molimm.2025.11.014","url":null,"abstract":"<div><h3>Background</h3><div>Verticinone, an alkaloid isolated from <em>Fritillaria</em>, exhibits a range of biological activities. This study aims to investigate the effects of verticinone on papillary thyroid carcinoma (PTC), the most prevalent histological type of thyroid cancer, as well as the potential mechanisms underlying these effects.</div></div><div><h3>Methods</h3><div>Cell counting kit-8, colony formation assay, and 5-ethynyl-2′-deoxyuridine staining were employed to evaluate the impact of verticinone on the proliferation capacity of PTC cells. Wound healing and Transwell assays were conducted to assess the effects of verticinone on the migration and invasion abilities of PTC cells. Flow cytometry was utilized to detect apoptosis in PTC cells. Western blot analysis was performed to measure the expression levels of relevant proteins. Additionally, network pharmacology analysis was conducted to identify potential targets of verticinone and thyroid carcinoma, and molecular docking was used to elucidate the targeting relationship. Finally, the effect of verticinone on tumor growth was evaluated using a xenograft tumor model.</div></div><div><h3>Results</h3><div>Verticinone inhibited the proliferation, migration, and invasion, and induced apoptosis and pyroptosis of PTC cells in a dose-dependent manner. Mechanically, verticinone targeted and inhibited protein kinase B (AKT), facilitating its degradation. AKT overexpression significantly eliminated the effect of verticinone on biological behavior of PTC cells. The results of xenograft tumor experiments demonstrated the inhibitory effect of verticinone on PTC tumor growth.</div></div><div><h3>Conclusion</h3><div>Verticinone inhibited the growth of PTC cells and induced pyroptosis by regulating the AKT pathway.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 41-52"},"PeriodicalIF":3.0,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145661462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coxsackievirus B3 regulates macrophage polarization through ANXA3 to promote the development of myocarditis","authors":"Yanfei Chen ,&nbsp;Xingzhu Liu ,&nbsp;Lijuan Meng ,&nbsp;Bin Li ,&nbsp;Zhongjian Su ,&nbsp;Li Jiang ,&nbsp;Yuqin Wu ,&nbsp;Xing Zhang","doi":"10.1016/j.molimm.2025.11.015","DOIUrl":"10.1016/j.molimm.2025.11.015","url":null,"abstract":"<div><h3>Background</h3><div>Viral myocarditis (VMC) is a common inflammatory disease in children that is caused mainly by Coxsackievirus B3 (CVB3) infection. M1 macrophage polarization is a key pathological event in the progression of CVB3-induced myocarditis, and annexin 3 (ANXA3) plays an important role in the process of macrophage activation. Therefore, this study aimed to investigate the function of ANXA3 in CVB3-induced myocarditis and macrophage polarization.</div></div><div><h3>Methods</h3><div>CVB3-challenged mice were used to establish a CVB3-induced myocarditis model, and the polarization of RAW264.7 cells was induced by CVB3 infection. The expression of genes and proteins was detected by RT–qPCR, western blotting, immunohistochemistry, immunofluorescence, and ELISA. The pathological lesions in the cardiac tissue were detected by HE staining. Serum levels of myocardial injury markers were detected using kits.</div></div><div><h3>Results</h3><div>We found that ANXA3 expression was increased in VMC. ANXA3 knockdown hindered the progression of CVB3-induced VMC, as manifested by increased body weight, reduced inflammatory cell infiltration in the heart, and decreased serum levels of myocardial injury markers (LDH, CK, CK-MB and cTnI). ANXA3 knockdown also inhibited the M1 polarization of CVB3-infected mouse heart tissue macrophages and RAW264.7 cells <em>in vitro</em> and reduced the levels of the inflammatory cytokines IL-1β, IL-6, and TNF-α. In addition, CVB3 infection promoted the expression of TLR4, MyD88, and p-IκB-α in mouse heart tissues and RAW264.7 cells and the nuclear transfer of NF-κB p65 and inhibited the expression of IκB-α. Mechanistic studies revealed that CVB3 increased ANXA3 expression by activating the TLR4/MyD88 pathway, thereby promoting NF-κB p65 nuclear translocation and the subsequent M1 polarization of macrophages, eventually leading to the development of CVB3-induced myocarditis.</div></div><div><h3>Conclusion</h3><div>Our study elucidated the role of ANXA3 in promoting CVB3-induced myocarditis, providing a potential intervention target for the treatment of VMC.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 68-81"},"PeriodicalIF":3.0,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"“Double-duty” dendritic cells in Xenopus laevis: Early vertebrate splenic APCs resemble conventional dendritic cells and limit native antigen presentation to B cells during a humoral response","authors":"Emily M. Flowers ,&nbsp;Xiwei Peng ,&nbsp;Erik J. Cruz ,&nbsp;Martin F. Flajnik","doi":"10.1016/j.molimm.2025.11.008","DOIUrl":"10.1016/j.molimm.2025.11.008","url":null,"abstract":"<div><div>XL cells are class II^hi, Ig-bearing cells found in splenic B cell follicles of the amphibian <em>Xenopus laevis</em>, bearing native antigen after immunization. XL cells are proposed to be myeloid cells serving the functions of both classical dendritic cells (cDC) and mammalian follicular dendritic cells (FDC). Here, we compare the function and gene expression of XL cells with peritoneal macrophages (pMac), which are also class II^hi/Ig-bearing cells. While pMacs were esterase-positive, adherent to plastic, and highly phagocytic, XL cells, like mammalian DC, adhered weakly to plastic, were esterase-low-to-negative, and were weakly phagocytic. Splenic red pulp macrophages, like pMacs, were esterase-positive. Both pMacs and XL cells bound to complement activated on zymosan particles. RNAseq was also done with IgY FACS-purified pMacs and XL cells. The pMac transcriptome was consistent with the classical macrophage lineage with high Mafb, myeloperoxidase, and CEBPA. In contrast, XL cells expressed cDC markers, chemokines CXCL13 and CCL19/CCL21, and the FDC marker VCAM1, consistent with their presumed function of attracting lymphocytes and presenting antigen. Mammalian FDC can present native antigen up to one year within B cell follicles, while ectotherms lack FDC but have myeloid cells that trap native antigen for unknown lengths of time. As shown previously, XL cells bear fluorescent antigen on their surface 16 days after immunization. However, we now show that antigen disappears by D30. Our data suggest that the myeloid XL cells indeed act as APC during a humoral immune response, but do not serve as an antigen depot to sustain memory B cells.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 53-67"},"PeriodicalIF":3.0,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145669330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}