Cellular immunology最新文献_第9页

Tim-3 promotes viral infection by suppressing the USP25-TRAF3-IRF7 signaling pathway Tim-3通过抑制USP25-TRAF3-IRF7信号通路促进病毒感染

IF 3.7 4区医学

Cellular immunology Pub Date : 2025-03-01 Epub Date: 2025-02-08 DOI: 10.1016/j.cellimm.2025.104930

Lin Du , Jinjie Chen , Chunxiao Du , Junrui Chen , Zhaoxiang Wang , Bing Bao , L.V. Zhonglin , Chen Xing , Meng Liang , Lanying Wang , Shun Xie , Yuxiang Li , Zhiding Wang , Ge Li , Jun Zhang , Gencheng Han

{"title":"Tim-3 promotes viral infection by suppressing the USP25-TRAF3-IRF7 signaling pathway","authors":"Lin Du , Jinjie Chen , Chunxiao Du , Junrui Chen , Zhaoxiang Wang , Bing Bao , L.V. Zhonglin , Chen Xing , Meng Liang , Lanying Wang , Shun Xie , Yuxiang Li , Zhiding Wang , Ge Li , Jun Zhang , Gencheng Han","doi":"10.1016/j.cellimm.2025.104930","DOIUrl":"10.1016/j.cellimm.2025.104930","url":null,"abstract":"<div><div>Tim-3, an immune checkpoint inhibitor, plays key roles in maintaining immune homeostasis and is involved in viral evasion. However, the precise role of Tim-3 in viral infection remains to be determined. USP25 is a deubiquitinating enzyme that initiates antiviral immunity by deubiquitinating TRAF3 and triggering the antiviral signaling pathway. Here we found that Tim-3-specific knockout in myeloid cells leads to enhanced antiviral immunity in mice with vesicular stomatitis virus (VSV) encephalitis by increasing the type I interferon response. Mechanistically, Tim-3 inhibits the expression of USP25 via STAT1 and interacts with USP25 but does not regulate its posttranslational modification; as a result, Tim-3 inhibits USP25-mediated deubiquitination of TRAF3, promotes K48-linked ubiquitination and degradation of TRAF3, inhibits the phosphorylation of IRF7, and ultimately downregulates the interferon response. These findings provide new insights into the function of Tim-3 in antiviral immunity and its related clinical significance.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"409 ","pages":"Article 104930"},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143395544","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 polarization of macrophages participates in the repair after folic acid-induced acute kidney injury 巨噬细胞极化参与叶酸诱导急性肾损伤后的修复

IF 3.7 4区医学

Cellular immunology Pub Date : 2025-03-01 Epub Date: 2025-02-10 DOI: 10.1016/j.cellimm.2025.104929

Shujie Yang , Yan Shen

{"title":"The polarization of macrophages participates in the repair after folic acid-induced acute kidney injury","authors":"Shujie Yang , Yan Shen","doi":"10.1016/j.cellimm.2025.104929","DOIUrl":"10.1016/j.cellimm.2025.104929","url":null,"abstract":"<div><div>Acute kidney injury (AKI) remains a major public health challenge, posing serious threats to human health. Increasing evidence indicates that renal cells undergo significant metabolic alterations following AKI, with inflammatory responses persisting throughout both injury and repair phases. Our previous research has demonstrated that heightened aerobic glycolysis after AKI leads to increased secretion of metabolic byproducts such as lactate, which plays a critical role in tissue repair. However, the relationship between metabolic reprogramming and inflammatory responses, as well as the underlying mechanisms, remain poorly understood. This study aims to clarify the regulatory effects of the glycolytic byproduct lactate on macrophage activation and phenotypic differentiation following AKI. We observed increased expression of M1/M2 macrophages and elevated secretion of inflammatory cytokines after folic acid-induced AKI. Immunofluorescence staining showed co-localization of macrophages with α-SMA. Manipulating lactate levels post-injury led to a decrease in macrophage expression and a reduction in fibroblast activation and proliferation, ultimately impairing renal tissue repair. These findings suggest that targeting lactate as a key regulator of macrophage phenotype differentiation may provide a theoretical and clinical foundation for therapeutic strategies in AKI repair.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"409 ","pages":"Article 104929"},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143376788","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

Effect of high-fat diet on IgA+ cells and BAFF/APRIL in small intestinal villous lamina propria of mice 高脂饲料对小鼠小肠固有绒毛层IgA+细胞和BAFF/APRIL的影响

IF 3.7 4区医学

Cellular immunology Pub Date : 2025-03-01 Epub Date: 2025-01-21 DOI: 10.1016/j.cellimm.2024.104911

Yuta Sakamoto , Masatoshi Niwa , Ken Muramatsu , Satoshi Shimo

{"title":"Effect of high-fat diet on IgA+ cells and BAFF/APRIL in small intestinal villous lamina propria of mice","authors":"Yuta Sakamoto , Masatoshi Niwa , Ken Muramatsu , Satoshi Shimo","doi":"10.1016/j.cellimm.2024.104911","DOIUrl":"10.1016/j.cellimm.2024.104911","url":null,"abstract":"<div><div>Obesity exacerbates susceptibility to infectious diseases. We investigated the effects of a high-fat diet (HFD) on intestinal immunity, particularly immunoglobulin (Ig)A-producing cells, B-cell activating factor (BAFF), and a proliferation-inducing ligand (APRIL) localization. Mice (4- to 20-weeks old) were fed HFD or standard chow diet, and their jejunum and ileum were fixed using the <em>in vivo</em> cryotechnique. Immunohistochemistry was performed for IgA, BAFF, and APRIL. In the HFD group, IgA<sup>+</sup>, IgA<sup>+</sup>CD22<sup>+</sup> (<em>p</em> < 0.001), and IgA<sup>+</sup>CD138<sup>−</sup> (<em>p</em> = 0.007) cell counts were diminished in the middle sections of the lamina propria of jejunal villi, and BAFF levels were significantly reduced in jejunal villi. The HFD effects on IgA<sup>+</sup> cell distribution seem to be confined to jejunal villi, hinting at localized vulnerabilities in intestinal immunity during obesity. Moreover, in the HFD group, IgA<sup>+</sup> B-cell counts were reduced in the middle jejunum, indicating inhibition of the IgA<sup>+</sup> B-cells through a T-cell-independent pathway.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"409 ","pages":"Article 104911"},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022320","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

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 : 2025-03-01 Epub 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":"10.1016/j.cellimm.2024.104913","url":null,"abstract":"<div><h3>Aims</h3><div>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.</div></div><div><h3>Main methods</h3><div>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.</div></div><div><h3>Key findings</h3><div>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.</div></div><div><h3>Significance</h3><div>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.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"409 ","pages":"Article 104913"},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","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

Breast cancer stem cells convert anti-tumor CD4+ T cells to pro-tumor T regulatory cells: Potential role of exosomal FOXP3 乳腺癌干细胞将抗肿瘤CD4+ T细胞转化为促肿瘤T调节细胞：外泌体FOXP3的潜在作用

IF 3.7 4区医学

Cellular immunology Pub Date : 2025-03-01 Epub Date: 2025-02-20 DOI: 10.1016/j.cellimm.2025.104931

Udit Basak , Sourio Chakraborty , Sumon Mukherjee , Subhadip Pati , Poulami Khan , Subhajit Ghosh , Arghya Adhikary , Kuladip Jana , Gaurisankar Sa , Tanya Das

{"title":"Breast cancer stem cells convert anti-tumor CD4+ T cells to pro-tumor T regulatory cells: Potential role of exosomal FOXP3","authors":"Udit Basak , Sourio Chakraborty , Sumon Mukherjee , Subhadip Pati , Poulami Khan , Subhajit Ghosh , Arghya Adhikary , Kuladip Jana , Gaurisankar Sa , Tanya Das","doi":"10.1016/j.cellimm.2025.104931","DOIUrl":"10.1016/j.cellimm.2025.104931","url":null,"abstract":"<div><div>Cancer progression and its treatment-response are regulated by the tumor microenvironment (TME). Tumor-initiating cancer stem cells (CSCs) remain in constant communication with the TME, and modulate it through several mechanisms. Here, from <em>in-silico</em> findings and analyzing breast cancer patient tissue-derived data, CSCs and Tregs were found to be positively correlated. Furthermore, our <em>in-silico</em> analyses highlighted a positive relationship between CSC genes and Treg signature marker, FOXP3, even in cancer cell lines that do not contain any T cell or Treg cells, thus raising the possibility of CSCs expressing FOXP3. Validating our hypothesis, higher expression of FOXP3, both at mRNA and protein levels, was observed in breast CSCs than non-stem cancer cells. Since a small population of CSCs initiate tumor in immune cell-dominated TME, we aimed at exploring whether breast CSCs directly transfer FOXP3 to CD4<sup>+</sup>T cells to generate immunosuppressive Treg cells. First, our search revealed CSC-derived exosomes (CDEs) generated CD4<sup>+</sup>CD25<sup>+</sup>FOXP3<sup>+</sup> Tregs at an early time-point of 24 h, which were immunosuppressive in nature. Next, detecting presence of FOXP3 protein in CDEs showed a strong possibility of FOXP3 transfer through CDEs. This was supported by detecting elevated FOXP3 levels from 12 h in translation inhibitor-treated T cells upon CDE-exposure. Finally, exosomes derived from FOXP3 attenuated-CSCs furnished lower FOXP3 in T cells than control CDEs. This mechanism was validated in <em>in-vivo</em> murine model. Together these results indicate a hitherto unexplored role of CSC-derived FOXP3 in reprogramming T cells into immunosuppressive Treg cells.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"409 ","pages":"Article 104931"},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453338","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 : 2025-03-01 Epub 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":"10.1016/j.cellimm.2024.104915","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>Using publicly available datasets, we performed bioinformatics analyses to identify <em>TMEM164</em>-regulated genes involved in ferroptosis. In addition, <em>in vitro</em> and <em>in vivo</em> assays were conducted to assess the impact of TMEM164 on cellular functions in NSCLC.</div></div><div><h3>Results</h3><div>Functional assays demonstrated that TMEM164 overexpression significantly inhibited invasion, migration, and cell proliferation in both <em>in vitro</em> and <em>in vivo</em> 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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"409 ","pages":"Article 104915"},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","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

Arctiin suppress Th17 cells response and ameliorates experimental autoimmune uveitis through JAK/STAT signaling 牛蒡子素抑制Th17细胞反应，通过JAK/STAT信号通路改善实验性自身免疫性葡萄膜炎。

IF 3.7 4区医学

Cellular immunology Pub Date : 2025-03-01 Epub 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":"10.1016/j.cellimm.2025.104927","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"409 ","pages":"Article 104927"},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","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 : 2025-03-01 Epub Date: 2025-01-17 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":"10.1016/j.cellimm.2025.104917","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"409 ","pages":"Article 104917"},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IL-17 family members exert an autocrine pro-inflammatory loop in CF respiratory epithelial cells ex vivo IL-17家族成员体外在CF呼吸上皮细胞中发挥自分泌促炎回路。

IF 3.7 4区医学

Cellular immunology Pub Date : 2025-03-01 Epub Date: 2025-01-17 DOI: 10.1016/j.cellimm.2025.104926

Caterina Allegretta , Enza Montemitro , Fabiana Ciciriello , Maria Teresa Altieri , Giuseppe Sabbioni , Giulia Breveglieri , Monica Borgatti , Giulio Cabrini , Onofrio Laselva

{"title":"IL-17 family members exert an autocrine pro-inflammatory loop in CF respiratory epithelial cells ex vivo","authors":"Caterina Allegretta , Enza Montemitro , Fabiana Ciciriello , Maria Teresa Altieri , Giuseppe Sabbioni , Giulia Breveglieri , Monica Borgatti , Giulio Cabrini , Onofrio Laselva","doi":"10.1016/j.cellimm.2025.104926","DOIUrl":"10.1016/j.cellimm.2025.104926","url":null,"abstract":"<div><h3>Background</h3><div>Lungs of people with Cystic Fibrosis (pwCF) are characterized by chronic inflammation and infection with <em>P. aeruginosa</em>. High levels of IL-17 A and F have been observed in sputum of pwCF and the interleukin-17(IL-17) family (A-to-F) has been suggested to play a key role in CF pulmonary disease.</div></div><div><h3>Methods</h3><div>We measured mRNA levels of IL-17 receptors (IL-17R) by RT-qPCR in CF bronchial epithelial (CFBE) cultured cells upon infection with <em>P. aeruginosa</em> PAO1 strain or clinical exoproducts (EXO) isolated from pwCF. We measured IL-17 mRNA expression by RT-qPCR and the release of cytokines by ELISA and Bioplex from CF primary nasal epithelial (HNE) cultured cells.</div></div><div><h3>Results</h3><div>Infection of CFBE cells with PAO1 or EXO isolated from 15 pwCF significantly increased mRNA expression of all IL-17R, except IL-17RD. Infection of HNE cells with EXO isolated from the correspondent donor significantly increased the mRNA levels of all the IL-17 cytokines and receptors, except for IL-17D and IL-17RD, and the release of the cytokines IL-17 A, IL-17B, IL-17C, IL-17E and IL-17F. HNE exposed to IL-17 A and F were induced to release pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), neutrophil chemokines (IL-8, G-CSF) and cytokines known to be involved in chloride and bicarbonate secretion, together with mucin upregulation (IL-4, IL-13).</div></div><div><h3>Conclusion</h3><div>These results highlight a wider expression of IL-17 family member in respiratory epithelial cells, which can play a role as an autocrine inflammatory amplification loop in CF airways. These in-vitro studies using patient-derived cultures underline the relevant role of IL-17 family members in CF pulmonary immune response.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"409 ","pages":"Article 104926"},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000839","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

In vitro ovarian tumor-conditioned CD163+ human macrophages retain phagocytic response to CD47 blockade 体外卵巢肿瘤条件CD163+人巨噬细胞对CD47阻断保持吞噬反应

IF 3.7 4区医学

Cellular immunology Pub Date : 2025-03-01 Epub Date: 2025-02-17 DOI: 10.1016/j.cellimm.2025.104932

Kristian W. Antonsen , Anne G. Jensen , Boe S. Sorensen , Anders Etzerodt , Søren K. Moestrup , Holger J. Møller

{"title":"In vitro ovarian tumor-conditioned CD163+ human macrophages retain phagocytic response to CD47 blockade","authors":"Kristian W. Antonsen , Anne G. Jensen , Boe S. Sorensen , Anders Etzerodt , Søren K. Moestrup , Holger J. Møller","doi":"10.1016/j.cellimm.2025.104932","DOIUrl":"10.1016/j.cellimm.2025.104932","url":null,"abstract":"<div><h3>Introduction</h3><div>CD163-expressing macrophages are abundant in ovarian cancer where they accelerate tumor growth and metastasis. CD47 blockade is a novel immunotherapy aiming to activate macrophage phagocytosis of tumor cells, but it is currently unknown if the tumor-associated macrophages expressing CD163 respond poorly to CD47 blockade.</div></div><div><h3>Methods</h3><div>Human monocyte-derived macrophages were exposed to tumor-conditioned medium from A2780 ovarian cancer cells during differentiation. Effects on gene expression, membrane protein levels, release of soluble proteins and macrophage phagocytosis of A2780 cells in response to CD47 blockade were measured and compared to control macrophages.</div></div><div><h3>Results</h3><div>Tumor cell conditioning induced macrophage expression of CD163 on both the mRNA and protein level. Furthermore, tumor conditioning simultaneously increased protein expression of the phenotype markers CD206 and CD80, and the phagocytosis checkpoint LILRB1. However, tumor conditioning did not reduce phagocytic capacity, as CD47 blockade induced macrophage phagocytosis of A2780 cells to similar degrees in both control and tumor cell-conditioned macrophages.</div></div><div><h3>Discussion</h3><div>In vitro tumor conditioning did not reduce the phagocytic response to CD47 blockade, suggesting that induction of a macrophage phenotype with increased expression of CD163 does not directly limit the capacity for phagocytosis of tumor cells. In conclusion, these findings suggest that CD163+ macrophages remain responsive to CD47 blockade, highlighting their potential as targets for immunotherapy in ovarian cancer.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"409 ","pages":"Article 104932"},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464189","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