Molecular immunology最新文献

{"title":"Restoring NR4A3 function in neutrophils alleviates sepsis by limiting NF-κB-dependent NETs formation and organ damage","authors":"Si Li ,&nbsp;Chengwu Liu ,&nbsp;Caixia Wu ,&nbsp;Zhaoming Liu","doi":"10.1016/j.molimm.2025.11.013","DOIUrl":"10.1016/j.molimm.2025.11.013","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis, a life-threatening condition, involves excessive neutrophil extracellular traps (NETs) contributing to organ damage. The role of orphan nuclear receptor NR4A3 in modulating neutrophil NETosis via NF-κB during sepsis is poorly understood. This study aimed to elucidate NR4A3's function and therapeutic potential.</div></div><div><h3>Methods</h3><div>Single-cell RNA sequencing analysis was performed using GSE175453 and GSE167363 from GEO database, involving PBMCs from septic patients and controls. <em>In vitro</em>, ATRA-differentiated HL-60 neutrophils with NR4A3 overexpression were LPS-stimulated. <em>In vivo</em>, a cecal ligation and puncture (CLP) sepsis mouse model received AAV-mediated NR4A3 overexpression. Key readouts included NR4A3 expression, NF-κB activation, NETs markers (NE, CitH3, PADI4, MPO-DNA), inflammatory cytokines (TNF-α, IL-1β, IL-6), ROS generation, and intestinal tissue pathology.</div></div><div><h3>Results</h3><div>scRNA-seq analysis revealed significant NR4A3 downregulation in neutrophils from septic patients. In vitro, NR4A3 overexpression in neutrophils significantly attenuated LPS-induced NF-κB (p65) activation, NETs formation, inflammatory cytokine production, and ROS generation. In vivo, AAV-mediated NR4A3 overexpression in CLP-induced septic mice ameliorated intestinal inflammation, suppressed p65 phosphorylation and NETs-related markers in the intestine, and reduced systemic inflammatory cytokine levels.</div></div><div><h3>Conclusion</h3><div>Our findings demonstrate that NR4A3 exerts a protective role in sepsis by inhibiting the NF-κB signaling pathway in neutrophils, thereby suppressing excessive NETs formation and the associated inflammatory cascade. Thus, NR4A3 represents a promising therapeutic target for mitigating NET-driven pathology in sepsis.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 206-215"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145828053","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":"2026-01-01","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":"CD38 knockout attenuates type 2 diabetic renal injury by downregulating p53 and Bax via the ERK/JNK signaling pathway","authors":"Dan Li ,&nbsp;Yuna Du ,&nbsp;Huiqing Zhang,&nbsp;Hui Fang,&nbsp;Jing You,&nbsp;Qicheng Fan,&nbsp;Yiguo Chen,&nbsp;Zhe Fang,&nbsp;Rong Li","doi":"10.1016/j.molimm.2025.11.017","DOIUrl":"10.1016/j.molimm.2025.11.017","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic nephropathy (DN), the leading cause of end-stage renal disease (ESRD), imposes substantial burdens on patients' health and socioeconomic status. Although current therapies targeting blood pressure, glycemic control, and the renin-angiotensin system provide partial relief for DN, their efficacy remains limited. CD38, a 46-kilodalton type II transmembrane glycoprotein, is reported involved in the development of diabetes mellitus. However, the specific role and molecular mechanisms of CD38 in DN pathogenesis require further elucidation. This study aims to investigate these mechanisms.</div></div><div><h3>Methods</h3><div>Analyze the expression of CD38 in DN through the GEO database.Type 2 diabetic mouse models were established by using high-fat diet and streptozocin (STZ) injection. Four groups of mice were used in this experiment: WT group, DM group, CD38^-/- group and CD38^-/-+DM group. Body weight and fasting blood glucose were monitored longitudinally. After Post-euthanasia, kidney weight and body weight were weighed, then calculated kidney weight/body weight ratio. Renal tissues underwent histopathological evaluation (H&amp;E, PAS, PAM staining) and molecular analyses (immunohistochemistry, RT-qPCR, Western blot).</div></div><div><h3>Results</h3><div>CD38 expression was significantly higher (<em>P</em> &lt; 0.05) in DN than in normal humans. And CD38 deletion ameliorated renal histopathological injury in type 2 diabetic mice in H&amp;E staining, glycogen staining, PAM staining. RT-qPCR and Western blot results showed expressions of p53 and Bax in kidney tissues of CD38^-/-+DM group mice was significantly decreased (<em>P</em> &lt; 0.05) and Bcl-2 was significantly increased (<em>P</em> &lt; 0.01) compared with that of the DM group mice. Bax expression was decreased and Bcl-2 expression was increased in the renal tissues of mice of CD38^-/-+DM group when compared with mice in the DM group in immunohistochemical staining. CD38 deletion could alleviate ERK, JNK and p38 of MAPK signaling pathway(<em>P &lt; 0.05</em>). Inhibition of ERK and JNK in high glucose condition ameliorated apoptosis by down-regulating p53 and Bax (<em>P &lt; 0.05</em>).</div></div><div><h3>Conclusion</h3><div>CD38 deletion regulated body weight and fasting blood glucose, improved renal histopathological injury and apoptosis by inhibiting MAPK signaling pathway; CD38 deficiency alleviates diabetic nephropathy by inhibiting MAPK/p53-mediated apoptosis, highlighting its role as a potential therapeutic target.</div></div><div><h3>Clinical trial number</h3><div>Not applicable, and this study does not yet involve clinical data.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 31-40"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145661478","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":"2026-01-01","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":"Silence of circPLK1 inhibits NSCLC progression by regulating the miR-1294/SLC16A9 axis","authors":"Chuankui Li,&nbsp;Yifan Yang,&nbsp;Qicai Li,&nbsp;Guowen Wang,&nbsp;Tao Tao,&nbsp;Lixiang Li,&nbsp;Haiwei Sang","doi":"10.1016/j.molimm.2025.11.020","DOIUrl":"10.1016/j.molimm.2025.11.020","url":null,"abstract":"<div><h3>Background</h3><div>Non-small cell lung cancer (NSCLC) is the malignancy with the highest mortality worldwide. Circular RNA polo-like kinase 1 (<em>circPLK1</em>) is a circular RNA that involved in cancer progression. However, the role of <em>circPLK1</em> in NSCLC requires further investigation.</div></div><div><h3>Methods</h3><div>The expression of <em>circPLK1</em> in NSCLC cells was measured by using qRT-PCR. Bioinformatics analysis was performed to identify miRNAs that bind to <em>circPLK1</em> and the target mRNAs of these miRNAs. Cell viability, proliferation, apoptosis, migration, and invasion were assessed using CCK-8, colony formation, flow cytometry, and Transwell assays, respectively. Protein expression was evaluated by western blotting. Xenograft models were established to verify the regulatory role of circPLK1 in the miR-1294/SLC16A9 axis.</div></div><div><h3>Results</h3><div><em>circPLK1</em> was upregulaterd in NSCLC cells. Silencing <em>circPLK1</em> markedly inhibited cell viability, proliferation, migration, and invasion, while accelerating apoptosis in NSCLC cells. <em>circPLK1</em> acted as a sponge for <em>miR-1294</em> and promoted <em>SLC16A9</em> expression in NSCLC cells. Knockdown of <em>circPLK1</em> suppressed tumor growth in NSCLC by regulating the <em>miR-1294</em>/<em>SLC16A9</em> axis.</div></div><div><h3>Conclusion</h3><div><em>circPLK1</em> silence inhibited the proliferation, migration, and invasion of NSCLC cells by regulating the <em>miR-1294</em>/<em>SLC16A9</em> axis.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 216-225"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145828005","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":"2026-01-01","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":"“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":"2026-01-01","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}

{"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":"2026-01-01","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":"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":"2026-01-01","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":"Indole-3-propionic acid exerts radio-protective effects by modulating Wnt1/STAT3 pathway to alleviate oxidative stress and neuroinflammation in microglia","authors":"Yue Si ,&nbsp;Biying Zhang ,&nbsp;Jingjing Wei ,&nbsp;Mengyun Li ,&nbsp;Yong Liu ,&nbsp;Hongwei Ma","doi":"10.1016/j.molimm.2025.12.011","DOIUrl":"10.1016/j.molimm.2025.12.011","url":null,"abstract":"<div><div>Radiation-induced delayed brain injury (RIBI) refers to structural and functional brain alterations that develop several months to years after exposure to ionizing radiation (IR). Microglia activation-mediated neuroinflammation, as well as oxidative stress, constitutes a key factor contributing to RIBI. Indole-3-propionic acid (IPA) is an indole metabolite specifically produced by the tryptophan metabolism of gut microbiota. It can cross the blood-brain barrier and modulate the central nervous system (CNS). In order to explore the protective mechanism of IPA on IR-induced cerebral function, we studied the effect of IPA on the activation of BV2 microglia <em>in vitro</em>. The experimental results show that IPA can suppress the oxidative stress and inflammation of microglia, which is represented as upregulating the expression of antioxidant genes (<em>Hmox1</em>, <em>Ho-1</em>, and <em>Nqo1</em>), and reducing the mRNA levels of pro-inflammatory factors (<em>Tnf-α</em>, <em>Il-6</em>, <em>Inos</em>, and <em>Nox2</em>). This protective effect may be related to the inhibition of Wnt1 expression and STAT3 phosphorylation (p-STAT3 Y705; <em>p</em> = 0.0008) in microglia. Additionally, it was found that IPA could alleviate the IR-induced neuroinflammation and synaptic damage of mice, as evidenced by reduced serum TNF-α and IL-6 levels and widened postsynaptic density (PSD) thickness (<em>p</em> = 0.0239). Collectively, this study provides novel insights into the potential application of IPA in the therapeutic intervention of radiation-induced brain injury.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 192-205"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145820140","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}