Cellular immunology最新文献_第2页

Arctiin suppress Th17 cells response and ameliorates experimental autoimmune uveitis through JAK/STAT signaling.

IF 3.7 4区医学

Cellular immunology Pub Date : 2025-01-16 DOI: 10.1016/j.cellimm.2025.104927

Xiao'e Fan, Manhong Xu, Zhengmin Wang, Xiaoyan Sun, Yan Fan, Jiaqi Chen, Junpeng Hao, Ranran Wang, Wei Jia

{"title":"Arctiin suppress Th17 cells response and ameliorates experimental autoimmune uveitis through JAK/STAT signaling.","authors":"Xiao'e Fan, Manhong Xu, Zhengmin Wang, Xiaoyan Sun, Yan Fan, Jiaqi Chen, Junpeng Hao, Ranran Wang, Wei Jia","doi":"10.1016/j.cellimm.2025.104927","DOIUrl":"https://doi.org/10.1016/j.cellimm.2025.104927","url":null,"abstract":"<p><p>Conventional treatments for autoimmune uveitis, such as corticosteroids and systemic immunosuppressants, often result in adverse side effects, prompting the need for therapies targeting specific molecular pathways. This study investigates the effects of Arctiin, known for its diverse biological properties, on experimental autoimmune uveitis (EAU) through its action on Th17 cells and the JAK/STAT signaling pathway. Our findings reveal that Arctiin significantly alleviates EAU by reducing clinical scores, inflammatory cell infiltration, and levels of inflammatory cytokines like IL-17 and TNF-α in the eye. Arctiin achieves this by activating adiponectin receptor 1 (AdipoR1), which modulates the JAK/STAT pathway, thereby inhibiting Th17 cell differentiation and cytokine secretion. Additionally, Arctiin effectively suppresses IRBP-specific Th17 cell activation in cervical lymph nodes, further mitigating retinal inflammation and tissue damage. These results underscore Arctiin's potential as a therapeutic agent for uveitis and other autoimmune inflammatory disorders through the modulation of the AdipoR1/JAK/STAT pathway in Th17 cells.</p>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"409-410 ","pages":"104927"},"PeriodicalIF":3.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143037250","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}

引用次数: 0

The distinct characteristic of two peritoneal macrophage subsets in a mouse model of hepatocellular carcinoma presents a novel therapeutic strategy. 两种腹膜巨噬细胞亚群在肝癌小鼠模型中的独特特征提出了一种新的治疗策略。

IF 3.7 4区医学

Cellular immunology Pub Date : 2025-01-16 DOI: 10.1016/j.cellimm.2025.104917

Wan-Li Yang, Chao Yang, Nan Pang, Rui-Hua Yu, Kui-Yuan Tong, Feng Jiang

{"title":"The distinct characteristic of two peritoneal macrophage subsets in a mouse model of hepatocellular carcinoma presents a novel therapeutic strategy.","authors":"Wan-Li Yang, Chao Yang, Nan Pang, Rui-Hua Yu, Kui-Yuan Tong, Feng Jiang","doi":"10.1016/j.cellimm.2025.104917","DOIUrl":"https://doi.org/10.1016/j.cellimm.2025.104917","url":null,"abstract":"<p><p>The peritoneal cavity (PerC) is a discrete anatomical compartment housing diverse peritoneal macrophage subpopulations. Nonetheless, there exists a paucity of knowledge concerning the distinct functions of these subpopulations in the context of hepatocellular carcinoma (HCC) and their evolution throughout tumor advancement. This investigation seeks to analyze the characteristics of two principal peritoneal macrophage subpopulations, specifically large peritoneal macrophage (LPM) and small peritoneal macrophage (SPM), in the context of HCC. The results of our research indicate a significant decrease in the proportion of LPM during the progression of HCC, accompanied by an increase in the quantity of SPM. Furthermore, SPM found in ascites exhibited a macrophage phenotype that supports tumor growth in HCC. Importantly, the dynamic decrease of LPM in murine models following lipopolysaccharide (LPS) stimulation led to a decrease in survival rate, highlighting the critical role of the altered LPM to SPM ratio in HCC survival. By employing clodronate liposomes (CL) to deplete peritoneal macrophage in murine models, followed by the adoptive transfer of LPM, we effectively prolonged the survival of HCC and attenuated tumor progression. Our results suggest that a decrease in the LPM to SPM ratio correlates with increased mortality in the HCC model. On the contrary, the maintenance of a high ratio of LPM to SPM has shown a positive effect on HCC survival. These findings have enhanced our understanding of the complex interaction between different subpopulations of peritoneal macrophage in the development of HCC. Furthermore, these results have important implications for the development of novel therapeutic strategies.</p>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"409-410 ","pages":"104917"},"PeriodicalIF":3.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000845","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}

引用次数: 0

Deciphering the role of TMEM164 in autophagy-mediated ferroptosis and immune modulation in non-small cell lung cancer. 解读TMEM164在非小细胞肺癌自噬介导的铁凋亡和免疫调节中的作用。

IF 3.7 4区医学

Cellular immunology Pub Date : 2025-01-10 DOI: 10.1016/j.cellimm.2024.104915

Tahani Ahmad ALMatrafi

{"title":"Deciphering the role of TMEM164 in autophagy-mediated ferroptosis and immune modulation in non-small cell lung cancer.","authors":"Tahani Ahmad ALMatrafi","doi":"10.1016/j.cellimm.2024.104915","DOIUrl":"https://doi.org/10.1016/j.cellimm.2024.104915","url":null,"abstract":"<p><strong>Background: </strong>Non-small cell lung cancer (NSCLC) remains one of the most prevalent and deadly malignancies. Despite advancements in molecular therapies and diagnostic methods, the 5-year survival rate for lung adenocarcinoma patients remains unacceptably low, highlighting the urgent need for novel therapeutic strategies. Ferroptosis, a distinct form of regulated cell death, has emerged as a promising target in cancer treatment. This study investigates the role of TMEM164, a membrane protein, in promoting ferroptosis and modulating anti-tumor immunity in NSCLC, aiming to elucidate its therapeutic potential.</p><p><strong>Methods: </strong>Using publicly available datasets, we performed bioinformatics analyses to identify TMEM164-regulated genes involved in ferroptosis. In addition, in vitro and in vivo assays were conducted to assess the impact of TMEM164 on cellular functions in NSCLC.</p><p><strong>Results: </strong>Functional assays demonstrated that TMEM164 overexpression significantly inhibited invasion, migration, and cell proliferation in both in vitro and in vivo models. TMEM164 was also found to induce ferroptosis in NSCLC cells by promoting autophagy. Specifically, we identified a mechanism whereby TMEM164 mediates ATG5-dependent autophagosome formation, leading to the degradation of ferritin, GPX4, and lipid droplets. This degradation facilitated iron accumulation and lipid peroxidation, which triggered iron-dependent cell death. Notably, co-administration of TMEM164 upregulation and anti-PD-1 antibodies exhibited synergistic anti-tumor effects in a mouse model.</p><p><strong>Conclusion: </strong>These findings suggest that targeting TMEM164 to enhance ferroptosis and stimulate anti-tumor immunity may inhibit NSCLC progression. Consequently, TMEM164 holds promise as a new therapeutic target for NSCLC treatment.</p>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"409-410 ","pages":"104915"},"PeriodicalIF":3.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969706","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}

引用次数: 0

Natural killer cell-based therapies in neuroblastoma. 神经母细胞瘤的自然杀伤细胞疗法。

IF 3.7 4区医学

Cellular immunology Pub Date : 2025-01-01 Epub Date: 2024-11-28 DOI: 10.1016/j.cellimm.2024.104898

Abtin Ghasempour, Rashin Mohseni, Pouya Mahdavi Sharif, Amir Ali Hamidieh

引用次数: 0

KLHDC8A knockdown in normal ovarian epithelial cells promoted the polarization of pro-tumoral macrophages via the C5a/C5aR/p65 NFκB signaling pathway. 在正常卵巢上皮细胞中敲除 KLHDC8A 可通过 C5a/C5aR/p65 NFκB 信号通路促进促肿瘤巨噬细胞的极化。

IF 3.7 4区医学

Cellular immunology Pub Date : 2024-12-24 DOI: 10.1016/j.cellimm.2024.104913

Jie Fang, Jin Wang, Xinyue Zhao, Yaping Yang, Yujia Xiao

{"title":"KLHDC8A knockdown in normal ovarian epithelial cells promoted the polarization of pro-tumoral macrophages via the C5a/C5aR/p65 NFκB signaling pathway.","authors":"Jie Fang, Jin Wang, Xinyue Zhao, Yaping Yang, Yujia Xiao","doi":"10.1016/j.cellimm.2024.104913","DOIUrl":"https://doi.org/10.1016/j.cellimm.2024.104913","url":null,"abstract":"<p><strong>Aims: </strong>Tumor-associated macrophages (TAM) is related to Ovarian cancer (OC) pathogenesis, but the exact mechanism remains unclear. This study investigated the expression of Kelch Domain Containing 8 A (KLHDC8A) in OC and the mechanism associated with TAM.</p><p><strong>Main methods: </strong>Bioinformatics analysis of differential expression genes between normal and OC tissues were analyzed based on the Tumor Genome Atlas (TCGA) databases. KLHDC8A mRNA expression was knocked down in normal epithelial cells (IOSE80), and then the effects of siKLHDC8A on the proliferation, invasion, migration and C5a secretion of IOSE80 cells were explored. THP1-derived macrophages were cultured with medium of NC-IOSE80 cells, siKLHDC8A-IOSE80 cells with or without C5aR antagonists.</p><p><strong>Key findings: </strong>KLHDC8A was lowly expressed in OC and negatively correlated with the infiltration of tumor-promoting macrophages, contributing to the survival of OC patients. Furthermore, siKLHDC8A promotes the proliferation, invasion and migration of IOSE80 cells and leads to polarization of pro-tumoral macrophages, which can be rescued by C5aR antagonists.</p><p><strong>Significance: </strong>Our results indicated that KLHDC8A knockdown could modulate the development of OC by affecting macrophage polarization to pro-tumoral type via the C5a/C5aR/p65 NFκB signaling pathway. It may play an essential role as the tumor suppressor genes in diagnosis and treatment of OC.</p>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"409-410 ","pages":"104913"},"PeriodicalIF":3.7,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977827","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}

引用次数: 0

The CCL5/CCR5 axis in ulcerative colitis 溃疡性结肠炎中的 CCL5/CCR5 轴

IF 3.7 4区医学

Cellular immunology Pub Date : 2024-11-14 DOI: 10.1016/j.cellimm.2024.104891

Fan Fan Qu , Ya Qian Wu , Jian Bin Ji , Lin Yan , Jing Jing Wei , Qing Chao Song , Bao Qing Xu , Ming Cheng , Zheng Hua Zhou

引用次数: 0

Immunomodulation by galectin-9: Distinct role in T cell populations, current therapeutic avenues and future potential galectin-9 的免疫调节作用：在 T 细胞群中的独特作用、当前的治疗途径和未来的潜力。

IF 3.7 4区医学

Cellular immunology Pub Date : 2024-11-13 DOI: 10.1016/j.cellimm.2024.104890

Eva M. Gossink , Paul J. Coffer , Alessandro Cutilli , Caroline A. Lindemans

{"title":"Immunomodulation by galectin-9: Distinct role in T cell populations, current therapeutic avenues and future potential","authors":"Eva M. Gossink , Paul J. Coffer , Alessandro Cutilli , Caroline A. Lindemans","doi":"10.1016/j.cellimm.2024.104890","DOIUrl":"10.1016/j.cellimm.2024.104890","url":null,"abstract":"<div><div>Galectins, glycan-binding proteins, have been identified as critical regulators of the immune system. Recently, Galectin-9 (Gal-9) has emerged as biomarker that correlates with disease severity in a range of inflammatory conditions. However, Gal-9 has highly different roles in the context of immunoregulation, with the potential to either stimulate or suppress the immune response. Neutralizing antibodies targeting Gal-9 have been developed and are in early test phase investigating their therapeutic potential in cancer. Despite ongoing research, the mechanisms behind Gal-9 action remain not fully understood, and extrapolating the implications of targeting this molecule from previous studies is challenging. Here, we examine the pleiotropic function of Gal-9 focusing on conventional T lymphocytes, providing a current overview of its immunostimulatory and immunosuppressive roles. In particular, we highlight that Gal-9 differentially regulates immune responses depending on the context. Considering this complexity, further investigation of Gal-9′s intricate biology is necessary to define therapeutic strategies in immune disorders and cancer treatment aimed at inducing or inhibiting Gal-9 signaling.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"407 ","pages":"Article 104890"},"PeriodicalIF":3.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686098","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}

引用次数: 0

Ubiquitination and degradation of MHC-II by Tim-3 inhibits antiviral immunity Tim-3 对 MHC-II 的泛素化和降解抑制了抗病毒免疫。

IF 3.7 4区医学

Cellular immunology Pub Date : 2024-11-07 DOI: 10.1016/j.cellimm.2024.104889

Jie Zhou , Zhonglin LV , Meichen Liu , Chunxiao Du , Lin Du , Zhenfang Gao , Ziying Jiang , Lanying Wang , Shuohua Wang , Meng Liang , Shun Xie , Yuxiang Li , Zhiding Wang , Ge Li , Yinxiang Wei , Gencheng Han

{"title":"Ubiquitination and degradation of MHC-II by Tim-3 inhibits antiviral immunity","authors":"Jie Zhou , Zhonglin LV , Meichen Liu , Chunxiao Du , Lin Du , Zhenfang Gao , Ziying Jiang , Lanying Wang , Shuohua Wang , Meng Liang , Shun Xie , Yuxiang Li , Zhiding Wang , Ge Li , Yinxiang Wei , Gencheng Han","doi":"10.1016/j.cellimm.2024.104889","DOIUrl":"10.1016/j.cellimm.2024.104889","url":null,"abstract":"<div><div>We previously reported that Tim-3, an immune checkpoint inhibitor, inhibits MHC-II expression, but the molecular mechanisms involved and the implications for antiviral immunity remain to be determined. Here, we found that during H1N1 infection, Tim-3 inhibits MHC-II expression in macrophages/microglia in vitro. Tim-3 interacts with MHC-II via its intracellular tail and induces proteasomal dependent degradation of MHC-II. In H1N1 infected macrophages/microglia, Tim-3 promotes the K48-linked ubiquitination of MHC-II via MARCH8, a ubiquitin E3 ligase that can be upregulated by Tim-3. In H1N1 infected mice, specific knockout of Tim-3 in macrophages leads to a decreased viral load, attenuates tissue damage and increases the survival rate. We have thus identified a novel mechanism by which Tim-3 mediates virus immune escape. Manipulating the Tim-3-MHC-II signaling pathway may provide a novel treatment for viral infections.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"407 ","pages":"Article 104889"},"PeriodicalIF":3.7,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638491","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}

引用次数: 0

Gastrodenol suppresses NLRP3/GSDMD mediated pyroptosis and ameliorates inflammatory diseases Gastrodenol 可抑制 NLRP3/GSDMD 介导的脓毒症，改善炎症性疾病

IF 3.7 4区医学

Cellular immunology Pub Date : 2024-11-01 DOI: 10.1016/j.cellimm.2024.104888

Peipei Chen , Yunshu Wang , Huaiping Tang , Zhuo Liu , Jing Wang , Tingting Wang , Yun Xu , Sen-Lin Ji

{"title":"Gastrodenol suppresses NLRP3/GSDMD mediated pyroptosis and ameliorates inflammatory diseases","authors":"Peipei Chen , Yunshu Wang , Huaiping Tang , Zhuo Liu , Jing Wang , Tingting Wang , Yun Xu , Sen-Lin Ji","doi":"10.1016/j.cellimm.2024.104888","DOIUrl":"10.1016/j.cellimm.2024.104888","url":null,"abstract":"<div><div>Pyroptosis, a form of inflammatory programmed cell death, plays a pivotal role in the pathogenesis of various diseases. This process is primarily mediated by the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3). Gastrodenol (Bismuth tripotassium dicitrate, GAS) is a mineral compound which is used to treat duodenal and gastric ulcers associated with Helicobacter pylori. In this study, GAS was found to exhibit protective effects against classical pyroptosis in macrophages. Specifically, GAS effectively inhibits the activation of the NLRP3 inflammasome, Gasdermin D (GSDMD)-mediated pyroptosis, and the secretion of pro-inflammatory cytokines. Mechanistically, GAS inhibited NLRP3 oligomerization and reduced the oligomerization of adaptor protein apoptosis-associated speck like protein containing a caspase activation and recruitment domain (ASC) by directly binding to NLRP3. The interaction between GAS and NLRP3 is primarily mediated through hydrogen bonding and hydrophobic forces. Hydrogen bonds are formed with PHE-727, LEU-723, and ASP-700. Remarkably, GAS treatment attenuated pyroptosis-mediated inflammatory diseases, including experimental autoimmune encephalomyelitis (EAE), lipopolysaccharide (LPS)-induced septic, and monosodium urate (MSU)-induced peritonitis in mice. To conclude, this is the first report that discovered clinical old medicine GAS as a potent inhibitor of pyroptosis and propose a novel therapeutic strategy for the prevention and treatment of NLRP3-GSDMD mediated diseases.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"405 ","pages":"Article 104888"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560638","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}

引用次数: 0

Drug screening identifies pyrrolidinedithiocarbamate ammonium ameliorating DSS-induced mouse ulcerative colitis via suppressing Th17 differentiation 药物筛选发现吡咯烷二硫代氨基甲酸铵可通过抑制 Th17 分化改善 DSS 诱导的小鼠溃疡性结肠炎

IF 3.7 4区医学

Cellular immunology Pub Date : 2024-10-22 DOI: 10.1016/j.cellimm.2024.104887

Yu-e Guo , Jie Lv , Ping Shu , Xi Li , Ying Li , Junhong Guo , Guofang Chen , Yuping Li , Bo Lu , Wei Zhang , Yin Liu

{"title":"Drug screening identifies pyrrolidinedithiocarbamate ammonium ameliorating DSS-induced mouse ulcerative colitis via suppressing Th17 differentiation","authors":"Yu-e Guo , Jie Lv , Ping Shu , Xi Li , Ying Li , Junhong Guo , Guofang Chen , Yuping Li , Bo Lu , Wei Zhang , Yin Liu","doi":"10.1016/j.cellimm.2024.104887","DOIUrl":"10.1016/j.cellimm.2024.104887","url":null,"abstract":"<div><div>T helper 17 (Th17) cells play crucial roles in various autoimmune diseases, including ulcerative colitis (UC), which is characterized by widespread inflammation in the mucosa of the colon and rectum. To identify small-molecule compounds capable of inhibiting CD4<sup>+</sup> T cell differentiation into Th17 cells, we established a screening system. Through drug screening, we found that pyrrolidinedithiocarbamate ammonium (PDTC) effectively inhibits Th17 differentiation. In a dextran sulfate sodium (DSS)-induced UC mouse model, administration of PDTC significantly ameliorated colitis. PDTC treatment decreased the production of proinflammatory mediators and inhibited the proportion of Th17 cells in colitis-afflicted mice by suppressing NF-κB activation. These findings showed that PDTC can alleviate colitis by inhibiting NF-κB activation. The therapeutic effects of PDTC observed in a mouse model of UC provided a rationale for its application in clinical settings.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"405 ","pages":"Article 104887"},"PeriodicalIF":3.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142526061","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}

引用次数: 0