Immunobiology最新文献

{"title":"Immunophenotypic characteristics of Langhans giant cells and the role of CCR7 in their formation","authors":"Yumeng Jiang ,&nbsp;Yanqing Chen ,&nbsp;Gai Ge ,&nbsp;Zhenzhen Wang ,&nbsp;Yidie Zou ,&nbsp;Haiqin Jiang ,&nbsp;Hongsheng Wang","doi":"10.1016/j.imbio.2025.153086","DOIUrl":"10.1016/j.imbio.2025.153086","url":null,"abstract":"<div><div>Langhans giant cells (LGCs) play a crucial role in granulomatous diseases, yet their unique molecular characteristics and formation mechanisms remain unclear. In this study, we aimed to systematically characterize the molecular features of LGCs and reveal the role of CCR7 in their formation. Mouse bone marrow-derived macrophages (BMDMs) were induced and filtrated to obtain purified LGCs in vitro. RNA sequencing and bioinformatics analysis identified over 3000 differentially expressed genes (DEGs) between LGCs and M0 macrophages, with significant enrichment in cytokine-mediated signaling, extracellular matrix, and cytokine receptor activity. Immunophenotypic analysis revealed elevated expression of antigen-presenting molecules (CD80, CD86, CD40) in LGCs, particularly after <em>Mycobacterium marinum</em> infection. Further investigations demonstrated that CCR7 expression, along with its ligand CCL19, was significantly upregulated at both RNA and protein levels in LGCs compared to M0 macrophages. Small interfering RNA (siRNA) targeting CCR7 led to a marked reduction in LGC formation. Immunohistochemistry confirmed elevated CCR7 expression in LGCs from granuloma model mice and patients with mycobacterial infections. In conclusion, LGCs exhibit distinct molecular characteristics compared to M0 macrophages, with elevated antigen-presenting molecule expression and CCR7 involvement. CCR7 plays a crucial role in LGC formation, providing novel insights into granulomatous disease pathogenesis and potential therapeutic targets.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 4","pages":"Article 153086"},"PeriodicalIF":2.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144280479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated transcriptomic, metabolomic, and lipidomic analyses reveal a unique lipid profile of regulatory T cells upon activation","authors":"Yohei Sato ,&nbsp;Misa Yura ,&nbsp;Alana Chandler ,&nbsp;Yamato Hanawa ,&nbsp;Akihito Tsubota","doi":"10.1016/j.imbio.2025.153087","DOIUrl":"10.1016/j.imbio.2025.153087","url":null,"abstract":"<div><div>Regulatory T cells (Tregs) exhibit stable FOXP3 expression and regulate the immune response through suppressive activity. Their unique metabolic properties include increased glycolysis and oxidative phosphorylation. We combined transcriptomic, metabolomic, and lipidomic analyses to dissect the metabolic dynamics of Tregs upon activation. Combined metabolomic and lipidomic analyses showed that freshly isolated and activated Tregs had distinct metabolomic and lipidomic properties, respectively. Compared with activated effector T cells (Teffs), activated Tregs contained omega-3 long-chain polyunsaturated fatty acid (PUFA)-rich diglycerides and triglycerides. These were supported by transcriptomics data, showing upregulation of PPAR-alpha and PPAR-gamma. Compared with activated Teffs, activated Tregs exhibited greater ceramide production, consistent with the upregulation of ceramide synthase and sphingomyelin synthase. Confocal microscopy revealed that Tregs, in contrast to Teffs, were enriched in lysosomes and peroxisomes upon activation. Our data confirm the unique metabolic properties of Tregs, especially those characterized by omega-3 long-chain PUFA-rich triglycerides and ceramides, together with enriched lysosomes and peroxisomes, which correspond to metabolic alterations.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 4","pages":"Article 153087"},"PeriodicalIF":2.5,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144241240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial RNA/RIG-I promotes Caspase-1/GSDMD-mediated inflammation in sepsis-associated acute kidney injury","authors":"Jie Jiao ,&nbsp;Xuan Fang ,&nbsp;Lisha Ma ,&nbsp;Ruiqin Shen ,&nbsp;Dongmei Li ,&nbsp;Hao Luo ,&nbsp;Aiping Xu ,&nbsp;Zhaojun Xia ,&nbsp;Sheng Jin ,&nbsp;YunXia Shao ,&nbsp;Mengya Wang ,&nbsp;Decui Shao","doi":"10.1016/j.imbio.2025.153085","DOIUrl":"10.1016/j.imbio.2025.153085","url":null,"abstract":"<div><div>Mitochondria play a decisive role in the pathological mechanisms of acute kidney injury (AKI). However, the specific mechanisms by which mitochondria regulate inflammation in AKI remain elusive. We aimed to investigate the role of mitochondrial RNA (mtRNA) and retinoic acid-inducible gene I (RIG-I) in sepsis-induced renal injury. To establish an AKI mouse model, intraperitoneal injection of lipopolysaccharide was used. Meanwhile, NRK-52E cells were treated with lipopolysaccharide, ATP, and Nigericin (LAN). Western blotting and immunohistochemistry analyses revealed an upregulation of RIG-I expression in AKI samples. Depolarization of mitochondrial membrane potential and elevation of cytoplasmic mtRNA were observed after LAN treatment. RNA immunoprecipitation demonstrated a direct binding interaction between mtRNA and RIG-I. Additionally, mtRNA was shown to induce mitochondrial membrane potential depolarization, an effect that could be mitigated by RIG-I knockdown. It was observed that Caspase-1 and ASC associating with RIG-I through co-immunoprecipitation. The mitochondrial damage induced by LAN, along with the upregulation of caspase-1, cleaved caspase-1, GSDMD, and cleaved GSDMD, were mitigated by the knockdown of RIG-I. Additionally, GSDMD knockout attenuates lipopolysaccharide-induced renal injury and reduces the level of IL-1β and TNF-α in murine models. Our research indicates that the pathological processes of AKI are driven by mtRNA/RIG-I-mediated Caspase-1/GSDMD, leading to inflammation.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 4","pages":"Article 153085"},"PeriodicalIF":2.5,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144254337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phellodendrine chloride alleviates gouty arthritis through IL-6/STAT3 signaling pathway","authors":"Yu-yao Qin ,&nbsp;Zi-yi Qin ,&nbsp;Tao Liang ,&nbsp;Dong-er Qin ,&nbsp;Sheng-yi Hua ,&nbsp;Ming-hui Tan ,&nbsp;Shun Guo ,&nbsp;Fan Yang ,&nbsp;Le Shi ,&nbsp;Yun Yu ,&nbsp;Guang-ji Zhang","doi":"10.1016/j.imbio.2025.152918","DOIUrl":"10.1016/j.imbio.2025.152918","url":null,"abstract":"<div><h3>Background</h3><div>Phellodendrine, a primary bioactive constituent of Phellodendron chinense Schneid (PCS), is crucial in its pharmacological profile. Phellodendrine exhibits potent anti-nephritic properties and demonstrates a marked inhibitory effect on the cellular immune response. However, the effects of phellodendrine on proteoglycan depletion and cartilage degeneration in gouty arthritis remain insufficiently understood. Therefore, the objective of this study is to elucidate the therapeutic potential and underlying mechanisms of phellodendrine chloride (PC) in the treatment of gouty arthritis.</div></div><div><h3>Methods</h3><div>A monosodium urate (MSU)-induced arthritis model in rats, along with a peritonitis model in mice, was developed, in combination with a chondrocyte model. Neutrophil proportions were quantified using flow cytometry. The expression levels of MMP-3, STAT3, and phosphorylated STAT3 (p-STAT3) in chondrocytes were determined by Western blot analysis. Proteoglycan levels in chondrocytes were assessed using toluidine blue staining and quantitative reverse transcription PCR (qRT-PCR). Joint swelling rates were monitored at 0–24 h in rats, and histopathological changes in joint tissues were subsequently analyzed.</div></div><div><h3>Results</h3><div>Phellodendrine chloride mitigated the rise in neutrophil proportions within MSU-induced peritoneal lavage fluid in mice and decreased inflammatory cell infiltration in rat ankle tissues. Treatment with phellodendrine chloride led to a downregulation of MMP-3 protein levels and inhibited IL-1β-induced proteoglycan degradation in chondrocytes. Additionally, results from experiments combining IL-1β with AG490 or IL-6 demonstrated that phellodendrine chloride attenuated IL-1β-induced MMP-3 expression and proteoglycan degradation.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that phellodendrine chloride mitigates gouty arthritis (GA) by modulating the IL-6/STAT3 signaling pathway.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 4","pages":"Article 152918"},"PeriodicalIF":2.5,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144203476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"USP14 promotes osteoarthritis progression by deubiquitinating FZD8 to activate the Wnt/β-catenin signaling pathway","authors":"Xiaochao Chen,&nbsp;Tiancheng Ma,&nbsp;Yongfeng Chen,&nbsp;Qiang Sun,&nbsp;Huayi Wang,&nbsp;Yuanrui Wang","doi":"10.1016/j.imbio.2025.152905","DOIUrl":"10.1016/j.imbio.2025.152905","url":null,"abstract":"<div><h3>Background</h3><div>Osteoarthritis (OA) is a chronic degenerative disease and associated with multiple pathogenic factors, such as old age, heredity, obesity, mechanical damage and inflammatory gene mutation. In this study, we aimed to explore the functions of ubiquitin specific peptidase 14 (USP14) in OA development.</div></div><div><h3>Methods</h3><div>The <em>in vitro</em> model of OA was constructed by stimulating chondrocytes with IL-1β. qRT-PCR and western blot assays were used for gene expression. MTT assay and EdU assay were manipulated to evaluate cell proliferation. Flow cytometry analysis was conducted for cell apoptosis. ELISA kits were utilized to determine the concentrations of inflammatory cytokines. Co-immunoprecipitation (Co-IP) assay and GST pull-down assay were manipulated to estimate the interaction between USP14 and Frizzled 8 (FZD8). Ubiquitination assay was used to evaluate the deubiquitination of FZD8.</div></div><div><h3>Results</h3><div>USP14 was highly expression in OA cartilage tissues and IL-1β-triggered chondrocytes. USP14 silencing aggravated the proliferation and repressed the apoptosis, inflammation and extracellular matrix (ECM) degradation of IL-1β-treated chondrocytes. USP14 could interact with FZD8 and regulate FZD8 expression through FZD8 deubiquitination. Moreover, FZD8 overexpression alleviated the effects of UPS14 silencing on IL-1β-treated chondrocyte proliferation, apoptosis, inflammation and ECM degradation. Additionally, USP14 knockdown inhibited Wnt/β-catenin signal pathway via the deubiquitination of FZD8.</div></div><div><h3>Conclusion</h3><div>USP14 repressed IL-1β-treated chondrocyte proliferation and promoted apoptosis, inflammation and ECM degradation by regulating FZD8 expression and Wnt/β-catenin signal pathway.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152905"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of miR-146a in Th17 cells from rheumatoid arthritis patients and its correlation with inflammatory cytokines","authors":"Jinhui Tan ,&nbsp;Linghua Tan ,&nbsp;Hai Huang ,&nbsp;Bo Li","doi":"10.1016/j.imbio.2025.152916","DOIUrl":"10.1016/j.imbio.2025.152916","url":null,"abstract":"<div><div>To investigate the expression of miR-146a in peripheral blood T helper 17(Th17) cells of patients with rheumatoid arthritis (RA) and its correlation with inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-6(IL-6) and interleukin-17(IL-17)]. 50 patients with active RA who were treated in People's Hospital of Longhua, Shenzhen from July 2022 to June 2024 were selected, and 50 healthy people who underwent physical examination in the hospital during the same period were selected as healthy controls. Peripheral blood mononuclear cells(PBMCs) and Th cells were isolated from the venous blood of the subjects in the two groups. Quantitative real-time PCR (qPCR) was used to detect the expression of miR-146a in peripheral blood Th17 cells of the two groups, and flow cytometry (FCM) was used to detect the levels of TNF-α, IL-6 and IL-17. The peripheral blood Th17 cells of RA patients were transfected with miR-146a mimic, and the expression of miR-146a, TNF-α, IL-6 and IL-17 was detected again after transfection. Pearson correlation coefficient was used to analyze the correlation between miR-146a expression and TNF-α, IL-6, and IL-17 expression in RA patients before and after transfection. Before transfection of miR-146a mimic, the expression of miR-146a, TNF-α, IL-6, and IL-17 in peripheral blood Th17 cells of RA patients was higher than that of healthy controls(<em>P</em> = 0.000). After transfection, the expression level of miR-146a in peripheral blood Th17 cells of RA patients increased compared to before transfection, while the expressions of TNF-α, IL-6, and IL-17 decreased(<em>P</em> = 0.000). Pearson correlation analysis showed that the expression level of miR-146a in peripheral blood Th17 cells of RA patients before transfection was positively correlated with the expression levels of TNF-α, IL-6, and IL-17(<em>r</em> = 0.968, <em>P</em> = 0.000; <em>r</em> = 0.980, <em>P</em> = 0.000; <em>r</em> = 0.993, <em>P</em> = 0.000). After transfection, the expression level of miR-146a was also positively correlated with the expression levels of TNF-α, IL-6, and IL-17(<em>r</em> = 0.971, <em>P</em> = 0.000; <em>r</em> = 0.963, P = 0.000; <em>r</em> = 0.970, P = 0.000). miR-146a may participate in the pathogenesis of RA to some extent by affecting the secretion of TNF-α, IL-6, IL-17, and other related inflammatory cytokines by Th17 cells in peripheral blood of RA patients.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152916"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144137280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CH25H/25-HC promotes pulmonary fibrosis via AMPK/STAT6 pathway-dependent M2 macrophage polarization in COPD","authors":"Ying Li,&nbsp;Guangzhi Xiao,&nbsp;Xianghui Fu,&nbsp;Xing Luo,&nbsp;Fengfan Yang,&nbsp;Yadan Li,&nbsp;Zhaohui Zheng","doi":"10.1016/j.imbio.2025.152908","DOIUrl":"10.1016/j.imbio.2025.152908","url":null,"abstract":"<div><h3>Objective</h3><div>Chronic obstructive pulmonary disease (COPD) is intricately linked to pulmonary fibrosis, yet the underlying mechanisms remain unclear. This study investigates whether CH25H/25-hydroxycholesterol (25-HC) promotes pulmonary fibrosis in COPD by modulating AMPK/STAT6-dependent M2 macrophage polarization.</div></div><div><h3>Methods</h3><div>Using GEO datasets and a cigarette smoke-induced COPD mouse model, we analyzed CH25H expression and fibrotic pathology. CH25H was silenced via adeno-associated virus (AAV)-delivered shRNA. Histopathology, flow cytometry, qPCR, and Western blotting assessed fibrosis, macrophage polarization (M1/M2), and AMPK/STAT6 pathway activity. Bone marrow-derived macrophages (BMDMs) were employed to validate polarization mechanisms. The role of the AMPK/STAT6 pathway was investigated using the specific activator.</div></div><div><h3>Results</h3><div>Analysis of the GEO database and experimental verification showed significantly increased CH25H expression in both lung tissues and macrophages from COPD mice. CH25H knockdown alleviated alveolar damage, airway remodeling, and pulmonary fibrosis in COPD mice, evidenced by reduced expression of fibrosis-related proteins, improved lung function, and attenuated inflammatory responses. Moreover, CH25H knockdown inhibited M2 macrophage polarization and decreased the proportion of M2-type macrophages. Importantly, decreased levels of 25-HC following CH25H knockdown were asso ciated with suppressed activation of the AMPK/STAT6 pathway. Rescue experiments demonstrated that the protective effects of CH25H knockdown could be reversed by adding the AMPKα activator GSK621.</div></div><div><h3>Conclusion</h3><div>Our findings demonstrate that CH25H/25-HC exacerbates COPD-associated pulmonary fibrosis by promoting AMPK/STAT6-dependent M2 macrophage polarization. Targeting CH25H may represent a novel therapeutic strategy for mitigating fibrosis in COPD.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152908"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell RNA and TCR repertoire analysis identify markers of virus-specific T cells","authors":"Byung-Kwan Jeong ,&nbsp;Young-Ae Kim ,&nbsp;Jung-Wook Park ,&nbsp;Baknoon Ham ,&nbsp;Jihyeong Kim ,&nbsp;Gyungyub Gong ,&nbsp;Chae Lyul Lim ,&nbsp;Hee Jin Lee","doi":"10.1016/j.imbio.2025.152904","DOIUrl":"10.1016/j.imbio.2025.152904","url":null,"abstract":"<div><div>Adoptive cell therapy (ACT) is a promising method for treating cancer and viral infections. Identifying antigen-specific T cells (ASTs) is critical to ACT. We investigated biomarkers for identifying ASTs. Peripheral blood mononuclear cells from healthy donors underwent staining with carboxyfluorescein succinimidyl ester (CFSE) to detect proliferating ASTs. Following exposure to CMV pp65 peptide and interleukin-2 for T-cell expansion, CD3⁺/CD8⁺ T cells were isolated at varying time points, revealing distinct populations. TCR repertoire analysis unveiled nine major clones in CFSE⁻/CD3⁺/CD8⁺ T cells on day 7, constituting 93.9 % of total cells. Contrarily, CFSE⁺/CD3⁺/CD8⁺ T cells exhibited minimal overlap with major TCR clones. Combined single-cell RNA-seq analyses highlighted upregulated genes associated with cell cycle proliferation and T-cell cytotoxicity. Engineered T cells expressing dominant clones effectively engaged CMV pp65 peptide, triggering T-cell activation and interferon-γ production. A set of seven upregulated genes in CFSE⁻/CD3⁺/CD8⁺ T cells on day 7, indicative of proliferating ASTs, was used to identify antigen-specific CD3⁺/CD8⁺ T cells on days 2–3, exhibiting 93.52 % accuracy. These markers predicted CFSE⁻/CD3⁺/CD8⁺ T cells with dominant TCR clones following exposure to EBV peptide with 74.59 % accuracy. In conclusion, we identified new markers facilitating the early isolation of viral antigen-responsive T cells.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152904"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interpretable Machine Learning reveals the Role of PANoptosis in the Diagnosis and Subtyping of NAFLD","authors":"Feng Tian ,&nbsp;Yuqi Zhao ,&nbsp;Xinyang He ,&nbsp;Yu Zhang ,&nbsp;Minxuan Hu ,&nbsp;Yiwei Liang ,&nbsp;Ziyou Tian ,&nbsp;Yaxian Gao ,&nbsp;Yongwei Wang","doi":"10.1016/j.imbio.2025.152909","DOIUrl":"10.1016/j.imbio.2025.152909","url":null,"abstract":"<div><div>Non-alcoholic fatty liver disease (NAFLD) is a global health challenge characterized by complex pathogenesis and limited therapeutic options. Emerging evidence highlights PANoptosis—a coordinated interplay of pyroptosis, apoptosis, and necroptosis—as a critical driver of metabolic and immune dysregulation in NAFLD. Here, we integrated multiple datasets and interpretable machine learning to unravel the role of PANoptosis in NAFLD diagnosis, subtyping, and immune microenvironment remodeling. By intersecting differentially expressed genes and PANoptosis-related genes, we identified 9 hub genes (e.g., TRADD, CASP6, TNFRSF1A and TNFAIP3) and constructed a robust diagnostic model (AUC = 0.976) validated via SHAP analysis and nomogram. Unsupervised consensus clustering stratified NAFLD patients into two PANoptosis-driven subtypes (C1/C2 and CA/CB), revealing distinct immune cell infiltration patterns and pathway activation. Single-cell sequencing further localized hub genes to immune cells and revealed their cell communication, implicating their roles in the progression of NAFLD. Molecular docking studies identified fostamatinib and minocycline as potential therapeutic candidates, while pan-cancer analysis revealed that TNFRSF1A overexpression is associated with poor prognosis across multiple cancer types. This study enhances the understanding of PANoptosis as a crucial diagnostic and therapeutic target in NAFLD, providing novel insights into immune-mediated pathogenesis and paving the way for treatment strategies.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152909"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MAIT and iNKT cells in tissue homeostasis and repair","authors":"Rafael Almeida Paiva ,&nbsp;Marion Salou","doi":"10.1016/j.imbio.2025.152917","DOIUrl":"10.1016/j.imbio.2025.152917","url":null,"abstract":"<div><div>Mucosal-associated invariant T (MAIT) and invariant natural killer T (iNKT) are innate-like T cells, which develop in the thymus through an original developmental program leading to the acquisition of effector memory and tissue targeting phenotypes. Consequently, they become tissue-resident and quickly produce effector molecules both in a T cell receptor (TCR)-dependent manner after stimulation by activating antigens, and in a TCR-independent fashion in response to cytokines. The latter can trigger MAIT and iNKT cells similarly, potentially leading to redundant functions. MAIT and iNKT cells populate most peripheral tissues where they express a wide range of effector modules including immune type 1/2/17, regulatory and repair programs. This endows them with a plethora of functional properties from anti-infectious immunity to regulation of homeostatic processes and tissue repair. In this review, we summarize the current literature on how MAIT and iNKT cells maintain organ homeostasis and contribute to regeneration <em>in vivo</em>, mostly focused on adipose tissue, intestine, lung, liver and skin. Furthermore, we underline TCR- and/or cytokine-dependent mechanisms and potential redundant, non-redundant or even opposing functions.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152917"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}