Immunobiology最新文献

{"title":"High-dose Vitamin C inhibits PD-L1 expression by activating AMPK in colorectal cancer","authors":"Jia Huang,&nbsp;Su Min,&nbsp;Ruiyang Hong,&nbsp;Mou Zou,&nbsp;Dongyu Zhou","doi":"10.1016/j.imbio.2025.152893","DOIUrl":"10.1016/j.imbio.2025.152893","url":null,"abstract":"<div><div>Vitamin C (VitC) has elicited considerable interest regarding its potential role in cancer therapy; however, its effects on tumor immunity remain unclear. In colorectal cancer (CRC), although anti-PD-1/PD-L1 therapies demonstrate promise, their efficacy is still constrained. Our prior research demonstrated that VitC can inhibit tumor growth by suppressing the Warburg effect. This study aims to explore the effects of high-dose VitC on PD-L1 expression in CRC, focusing on its underlying mechanisms and potential for enhancing immunotherapy. We found that VitC inhibits aerobic glycolysis in HCT116 cells while also downregulating PD-L1 expression. Further investigations indicated that this process is mediated by VitC's activation of AMPK, which downregulates HK2 and NF-κB, ultimately resulting in reduced PD-L1 expression and increased T cell infiltration. Notably, we observed that VitC and the PD-L1 monoclonal antibody atezolizumab exhibit comparable tumor-inhibiting abilities, and their combined use further enhances this efficacy. In conclusion, our results demonstrate that high-dose VitC activates AMPK, downregulates PD-L1 expression, mitigates immune evasion, and suppresses tumor growth. This provides a promising strategy for optimizing immunotherapy in CRC.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152893"},"PeriodicalIF":2.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143681934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting B7-H3 in solid tumors: Development and evaluation of novel CAR-T Cell therapy","authors":"Ning Li ,&nbsp;Chunhua Zhang ,&nbsp;Xiaoyu Li ,&nbsp;Shufen Liu ,&nbsp;Youhua Xu ,&nbsp;Xifei Yang","doi":"10.1016/j.imbio.2025.152888","DOIUrl":"10.1016/j.imbio.2025.152888","url":null,"abstract":"<div><div>Ovarian and gastric cancers, representative of many solid tumors, remain among the most challenging malignancies to treat due to limited therapeutic options and poor outcomes at advanced stages. Although immunotherapies have revolutionized cancer treatment, their efficacy in solid tumors has been hindered by issues such as antigen heterogeneity and the immunosuppressive tumor microenvironment. This study presents the development and evaluation of third-generation chimeric antigen receptor T (CAR-T) cells targeting B7-H3, an immune checkpoint molecule widely overexpressed in solid tumors. The B7-H3 CAR-T cells exhibited robust and selective cytotoxicity against B7-H3-positive tumor cells, sparing normal tissues. In preclinical animal models, these cells significantly inhibited tumor growth, demonstrating higher targeting specificity and preferential accumulation in tumor sites. These results highlight B7-H3-targeted CAR-T cells as a potential breakthrough in immunotherapy for solid tumors, offering a foundation for future clinical trials to refine their safety and efficacy.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152888"},"PeriodicalIF":2.5,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143681933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Different doses of hydroxychloroquine regulate the structure of intestinal flora and glycosyltransferase activity in rats with IgA nephropathy","authors":"Lingling Bao,&nbsp;Xueyan Bian,&nbsp;Liling Ren,&nbsp;Sizeng Bao,&nbsp;Aiwei Zhang","doi":"10.1016/j.imbio.2025.152891","DOIUrl":"10.1016/j.imbio.2025.152891","url":null,"abstract":"<div><h3>Background</h3><div>Hydroxychloroquine (HCQ), by virtue of its ability to reduce proteinuria, is an alternative therapy for Immunoglobulin A nephropathy (IgAN). This study investigated the effects of different doses of HCQ on the structure of intestinal flora and glycosyltransferase activity in IgAN rats.</div></div><div><h3>Methods</h3><div>IgAN model rats constructed by treatment of bovine serum albumin, castor oil and lipopolysaccharide were administered with HCQ (18 or 36 mg/kg) by gavage. Then the number of urine erythrocyte and the renal function of rats were evaluated. The levels of galactose-deficient IgA1 (Gd-IgA1), B cell activation factor (BAFF) and C-reactive protein (CRP) in serum and those of inflammatory factors in renal tissue were detected by ELISA. Renal tissue injury and IgA deposition were assessed by histological analysis. The expressions of Core 1 beta1,3-galactosyltransferase (C1GALT1), Core 1 synthase specific molecular chaperone (COSMC) and ST6 <em>N</em>-acetylgalactosaminide alpha-2,6-sialyltransferase 2 (ST6GALNAC2) were quantified by qRT-PCR, Western blot or in vitro enzyme assays. 16 s rDNA sequencing was used to analyze the structure of intestinal flora in rats.</div></div><div><h3>Results</h3><div>HCQ dose-dependently decreased the levels of serum creatinine, UREA, Gd-IgA1, BAFF, CRP and urine protein, waned the number of urine erythrocyte, inhibited the expressions of inflammatory factors and IgA deposition in renal tissue, and up-regulated the expressions of C1GALT1, COSMC and down-regulated ST6GALNAC2 expression in peripheral blood mononuclear cells (PBMCs).</div></div><div><h3>Conclusion</h3><div>HCQ could reduce glomerular swelling in mesangial area and improve the imbalance of intestinal flora in IgAN rats.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152891"},"PeriodicalIF":2.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Suppression of astrocyte elevated gene-1 protects against light-induced photoreceptor apoptosis and inflammation in retina","authors":"Xinran Gao ,&nbsp;Haoran Qiao","doi":"10.1016/j.imbio.2025.152889","DOIUrl":"10.1016/j.imbio.2025.152889","url":null,"abstract":"<div><h3>Purpose</h3><div>To research the function of astrocyte elevated gene-1 (AEG-1) in light-induced retinal degeneration.</div></div><div><h3>Methods</h3><div>The retinas of BALB/c mice and 661W cells damage were induced by exposure to light; Lipopolysaccharide (LPS) was used to stimulate BV2 cells. AEG-1 siRNA transfection was used to inhibit AEG-1. Expressions of AEG-1, TLR4, TNF-α, phosphor-NF-κB (p-NF-κB) and total NF-κB (t-NF-κB) were detected. Photoreceptor apoptosis was evaluated by flow cytometry or TUNEL. Histological analyses were performed by hematoxylin and eosin (HE) staining.</div></div><div><h3>Results</h3><div>AEG-1 was highly expressed in light damaged (LD) retinas. The photoreceptor apoptosis and the thinning of outer nuclear layer (ONL) were inhibited by AEG-1 siRNA in LD mice retinas. The AEG-1 siRNA pretreatment significantly down-regulated the elevated expression levels of TLR4, p-NF-κB and TNF-α induced by LD in retinas. In vitro, AEG-1 was upregulated in 661W cells induced by LD and in BV2 cells stimulated by LPS. The AEG-1 siRNA prevented light induced apoptosis of 661W cells, and down-regulated the elevated expressions of TLR4, p-NF-κB and pro-inflammatory cytokine TNF-α caused by LPS in BV2 cells.</div></div><div><h3>Conclusions</h3><div>AEG-1 is highly expressed in retinal degeneration caused by LD. Suppression of AEG-1 protects against photoreceptor apoptosis and rescues the thinning of ONL in LD retinas. Suppression of AEG-1 also diminishes inflammation in light induced retinal degeneration, which may be regulated through the NF-κB pathway. Therefore, AEG-1 perhaps become a potential therapeutic target for this type of retinal degenerative disease.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152889"},"PeriodicalIF":2.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143636941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of cellular immune phenotype of peripheral blood mononuclear cells in Bangladeshi children with severe acute malnutrition","authors":"Zannatun Noor ,&nbsp;Shaumik Islam ,&nbsp;Md. Mehedi Hasan ,&nbsp;Ar-Rafi Khan ,&nbsp;Md Amran Gazi ,&nbsp;Farzana Hossaini ,&nbsp;Rashidul Haque ,&nbsp;Tahmeed Ahmed ,&nbsp;Mustafa Mahfuz","doi":"10.1016/j.imbio.2025.152887","DOIUrl":"10.1016/j.imbio.2025.152887","url":null,"abstract":"<div><div>Children suffering from severe acute malnutrition (SAM) have a weakened immune system. The relationship between malnutrition and alterations in the frequency of peripheral blood mononuclear cells (PBMCs) remains unclear. This study investigated the altered immune responses in Bangladeshi children with SAM compared to healthy children. PBMCs were collected from 24 healthy children and 25 children with SAM upon their hospital admission and after 21 days of nutritional therapy at a nutritional rehabilitation unit. Flow cytometry was employed to assess various subsets of T cells, B cells, and natural killer (NK) cells. Children with SAM exhibited significantly lower levels of activated (CD25+) B cells (SAM vs. healthy: 0.18 % vs. 0.30 %, <em>p</em> = 0.031) and NK cells (SAM vs. healthy: 4.9 % vs. 9.6 %, <em>p</em> = 0.003) compared to healthy controls. Similar immune responses were observed in SAM children during both hospitalization and discharge, with NK cell percentages showing slight increases but remaining significantly lower than in healthy children (SAM endline vs. healthy: 5.9 % vs. 9.6 %, <em>p</em> = 0.032). Notable reductions were also observed in CD62+ helper T cells, CD62L+ cytotoxic T cells, and CD62L+ B cells. These results suggest that although SAM children recover clinically, their immune systems remain compromised during discharge.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152887"},"PeriodicalIF":2.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing miR-16-5p-Loaded Exosomes from Adipose-Derived Stem Cells to Restore Immune Homeostasis in SLE Patients","authors":"Yin-hong Zhang ,&nbsp;Juan Chen ,&nbsp;Wen-fei Mao ,&nbsp;Li-xi Yan ,&nbsp;Fei Long ,&nbsp;Sheng-hao Li ,&nbsp;Rui-xian Zhang","doi":"10.1016/j.imbio.2025.152885","DOIUrl":"10.1016/j.imbio.2025.152885","url":null,"abstract":"<div><h3>Background</h3><div>Systemic Lupus Erythematosus (SLE) is an autoimmune disorder marked by an imbalance between pro-inflammatory Th17 cells and regulatory T cells (Tregs), which contributes to chronic inflammation and multi-organ damage, necessitating novel therapeutic strategies.</div></div><div><h3>Methods</h3><div>This study investigates the potential of adipose-derived stem cell (ADSC) exosomes to modulate the Th17/Treg balance in SLE patients through the miR-16-5p/LATS1 axis. Flow cytometry, ELISA, and quantitative real-time PCR were utilized to assess immune cell populations and cytokine levels in SLE patients. Additionally, ADSC exosomes were isolated and characterized, and their impact on CD4+ T cells was evaluated using dual-luciferase and Western blot assays.</div></div><div><h3>Results</h3><div>SLE patients exhibited increased Th17 cells and decreased Tregs, with corresponding changes in cytokine levels. Reduced miR-16-5p expression was noted in CD4+ T cells, correlating positively with Treg proportions. ADSC-derived exosomes were shown to deliver miR-16-5p effectively, targeting and downregulating LATS1 expression. This modulation restored the Th17/Treg balance and adjusted cytokine expression, indicating an immune regulatory effect.</div></div><div><h3>Conclusion</h3><div>ADSC-derived exosomes, through the miR-16-5p/LATS1 axis, offer a promising therapeutic approach for SLE by restoring immune equilibrium. This study highlights the potential of exosome-based therapies in modulating immune responses, providing a foundation for developing innovative treatments for autoimmune diseases.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152885"},"PeriodicalIF":2.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143580566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the Role of Oligosaccharyltransferase STT3B in Colorectal Cancer Tissues: Clinical significance and Molecular Mechanisms Driving the Formation of Tertiary Lymphoid Structures","authors":"Caixia Zhang ,&nbsp;Bin Wang ,&nbsp;Xiaofeng Bian ,&nbsp;Youcai Zhao ,&nbsp;Xiaobing Yang ,&nbsp;Wei Zhao","doi":"10.1016/j.imbio.2025.152886","DOIUrl":"10.1016/j.imbio.2025.152886","url":null,"abstract":"<div><div>The role of tertiary lymphatic structures (TLS) in anti-tumor response has garnered increasing attention; however, the clinical implications and regulatory mechanisms of various TLS subtypes remain poorly understood. This study investigates the function of the oligosaccharyltransferase subunit STT3B in modulating TLS formation and B cell activity within colorectal cancer (CRC) tissues. Spatial morphology analysis was employed to accurately identify the localization of STT3B expression within TLS. By integrating clinical samples with bioinformatics analyses, we examined the expression levels and distribution patterns of STT3B in the CRC microenvironment and assessed its clinical significance. Transcriptome sequencing, combined with <em>in vitro</em> validation, was utilized to evaluate the effects of STT3B knockdown on B cell functionality. The findings indicated that CRC patients with a high density of STT3B expression in the TLS had a better prognosis. Multicolor fluorescence analysis further demonstrated that the density of STT3B⁺CD19⁺ B cells correlated with pathological characteristics and lymph node metastasis status in CRC patients, with higher densities predicting longer disease-free survival. Transcriptome sequencing further demonstrated that STT3B knockdown predominantly impacts B cell metabolic functions. <em>In vitro</em> experiments confirmed that the downregulation of STT3B inhibits the metabolism and proliferation of B cells. These findings suggest that STT3B plays a crucial role in enhancing B cell metabolism and facilitating the development of mature TLS, which is associated with improved prognostic outcomes in patients with CRC.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152886"},"PeriodicalIF":2.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Renqing Changjue alleviates sepsis-induced acute lung injury by regulating renin-angiotensin system and inhibiting inflammatory response","authors":"Minxia Zhu ,&nbsp;Yaqi Lei ,&nbsp;Zhaojun Zhang ,&nbsp;Xu Guo ,&nbsp;Jing Guo ,&nbsp;Ruipeng Wu ,&nbsp;Xiaofeng Li ,&nbsp;Shibo Tian ,&nbsp;Yuanhao Zhao","doi":"10.1016/j.imbio.2025.152883","DOIUrl":"10.1016/j.imbio.2025.152883","url":null,"abstract":"<div><div>Sepsis, with high morbidity and mortality, represents a systemic inflammatory response syndrome. A common consequence of sepsis is acute lung injury (ALI). Renqing Changjue (RQCJ), a renowned prescription in traditional Tibetan medicine, is reported to have anti-inflammatory effects. The present study was aimed at exploring whether RQCJ could mitigate sepsis-induced ALI and elucidating its underlying mechanism. The rat model of sepsis-induced ALI was established by intraperitoneal injection of lipopolysaccharide (LPS), and high, medium, and low doses of RQCJ were administered. The results indicated that the intervention of RQCJ improved septic symptoms, mitigated the murine sepsis score and pulmonary edema in LPS-induced septic rats, and decreased inflammatory cytokines in lung tissue such as interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1). Furthermore, RQCJ regulated the balance of renin-angiotensin system by enhancing the enzyme activity of angiotensin converting enzyme 2 (ACE2) while inhibiting ACE, thereby promoting the production of angiotensin 1–7 (Ang1–7). This study highlights the multiple protective effects of RQCJ on sepsis-induced ALI, providing a valuable reference for its further development and offering a novel perspective for the treatment of sepsis-induced ALI.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152883"},"PeriodicalIF":2.5,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CVB3 regulates Treg cell pyroptosis through the lncRNA XIST/miR-195-5p/caspase-1 molecular axis","authors":"Yan Zhang ,&nbsp;Lei Yang ,&nbsp;Huiting Mu ,&nbsp;Na Li ,&nbsp;Xuejia Wang ,&nbsp;Hualan Lei ,&nbsp;Mingjie Pang","doi":"10.1016/j.imbio.2025.152882","DOIUrl":"10.1016/j.imbio.2025.152882","url":null,"abstract":"<div><div>Viral myocarditis (VMC) is characterized by severe cardiac inflammation and is a major cause of congestive heart failure and sudden cardiac death in healthy young people. The lncRNA XIST plays an important regulatory role in myocardial injury, but its role in VMC caused by coxsackievirus B3 (CVB3) infection is unclear. In this study, we evaluated the effects of the lncRNA XIST on a CVB3-induced VMC mouse model and on pyroptosis in CVB3-exposed Treg cells. The results showed that in CVB3-infected VMC and Treg cells, the expression level of the lncRNA XIST was increased, whereas miR-195-5p expression was decreased. In CVB3-induced VMC mice, inflammation was elevated, whereas the Treg/Th17 ratio was reduced. Knocking down the lncRNA XIST suppressed pyroptosis in Treg cells caused by CVB3 infection and inhibited VMC progression in vivo. Studies on downstream mechanisms have shown that the lncRNA XIST targets miR-195-5p, induces caspase-1 expression through the inhibition of miR-195-5p, promotes the expression of the inflammatory factors IL-1β and IL-18 associated with pyroptosis, inhibits the secretion of the anti-inflammatory factors IL-10 and TGF-β1, and ultimately promotes pyroptosis in Treg cells. In conclusion, knocking down the lncRNA XIST inhibits CVB3-induced pyroptosis of Treg cells and VMC progression in mice induced by CVB3 infection. These findings provide a potential theoretical basis for the treatment of VMC.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 2","pages":"Article 152882"},"PeriodicalIF":2.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical models of immune checkpoint inhibitors-related interstitial pneumonia for anti-PD1 tumor immunotherapy","authors":"Tingyue Luo ,&nbsp;Weisheng Chen ,&nbsp;Danhui Huang ,&nbsp;Xiguang Liu ,&nbsp;Junjie Xi ,&nbsp;Zeyu Fu ,&nbsp;Junwei Chen ,&nbsp;Yuhan Du ,&nbsp;Ruijun Cai ,&nbsp;Qi Yu ,&nbsp;Dongyu Liu ,&nbsp;Jiangzhou Du ,&nbsp;Laiyu Liu ,&nbsp;Shaoxi Cai ,&nbsp;Hangming Dong","doi":"10.1016/j.imbio.2025.152884","DOIUrl":"10.1016/j.imbio.2025.152884","url":null,"abstract":"<div><div>Immune-related adverse reactions (irAEs) are common adverse reactions after immune checkpoint inhibitor treatment, impacting the universality and continued use of immunotherapy. Currently, preclinical models to investigate the mechanisms underlying these adverse effects are inadequate. This study aims to develop both in vitro and in vivo models of irAEs to advance basic research on these adverse reactions. For vitro models, we designed two co-culture systems: “Lung epithelial cells-PBMC” conditional co-culture model and “organoid-PBMCs” co-culture model. These involve culturing spheroids, patient-derived organoids and isolating, expanding, and co-culturing peripheral blood mononuclear cells (PBMCs). For vivo model, PD1 humanized mice were used to establish a lung carcinoma in situ model in offspring, with blocked immune checkpoints to induce systemic inflammatory responses. Mice without PD-1 blockade served as the control group. In both organoid and “lung epithelial cell-PBMC” models, compared with the control group, the PBMC+anti-PD1 group exhibited inflammatory injury, demonstrated by the worst activity, increased collagen deposition, elevated mRNA levels of αSMA and Vimentin, higher Fibronectin expression, and higher inflammatory factors (IL6, IL1β, MPO) in the culture supernatant (<em>p</em> &lt; 0.05). In vivo model also showed pulmonary inflammation, with slower weight gain of the affected mice, more obvious pulmonary interstitial thickening(Masson staining and α-SMA immunofluorescence staining), and increased immune cells and IL17A in alveolar lavage fluid and serum. This study successfully developed preclinical models of irAEs using organoid technology, conditioned co-culture and humanized mouse models, effectively reproducing inflammatory injury and offering valuable tools for irAE research.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 2","pages":"Article 152884"},"PeriodicalIF":2.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}