Pub Date : 2025-01-21DOI: 10.1016/j.cellimm.2024.104911
Yuta Sakamoto , Masatoshi Niwa , Ken Muramatsu , Satoshi Shimo
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 in vivo cryotechnique. Immunohistochemistry was performed for IgA, BAFF, and APRIL. In the HFD group, IgA+, IgA+CD22+ (p < 0.001), and IgA+CD138− (p = 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+ cell distribution seem to be confined to jejunal villi, hinting at localized vulnerabilities in intestinal immunity during obesity. Moreover, in the HFD group, IgA+ B-cell counts were reduced in the middle jejunum, indicating inhibition of the IgA+ B-cells through a T-cell-independent pathway.
{"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":"2025-01-21","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}
Lungs of people with Cystic Fibrosis (pwCF) are characterized by chronic inflammation and infection with P. aeruginosa. 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.
Methods
We measured mRNA levels of IL-17 receptors (IL-17R) by RT-qPCR in CF bronchial epithelial (CFBE) cultured cells upon infection with P. aeruginosa 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.
Results
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).
Conclusion
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.
{"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":"2025-01-17","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}
Pub Date : 2025-01-17DOI: 10.1016/j.cellimm.2025.104917
Wan-Li Yang , Chao Yang , Nan Pang , Rui-Hua Yu , Kui-Yuan Tong , Feng Jiang
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.
{"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":"2025-01-17","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}
Pub Date : 2025-01-16DOI: 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
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.
{"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":"2025-01-16","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}
Pub Date : 2025-01-10DOI: 10.1016/j.cellimm.2024.104915
Tahani Ahmad ALMatrafi
Background
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.
Methods
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.
Results
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.
Conclusion
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.
{"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":"2025-01-10","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}
Pub Date : 2025-01-01DOI: 10.1016/j.cellimm.2024.104898
Abtin Ghasempour, Rashin Mohseni, Pouya Mahdavi Sharif, Amir Ali Hamidieh
Neuroblastoma (NB) is the most common extracranial solid tumor of childhood forming around 15 % of all pediatric tumors. Despite advances in the treatment of NB, high-risk patients still face a grave prognosis. Adoptive cell therapies based on NK cells are becoming an assistive treatment for such cases. Moreover, there is also evidence that NKT-based therapies have promising results in the management of NB. Lower complications in comparison with adoptive T cell therapies, various cell sources, and miscellaneous tumor recognition mechanisms are some of the advantages of NK- and NKT-based therapies. This review is dedicated to searching for recent advances in this field.
{"title":"Natural killer cell-based therapies in neuroblastoma","authors":"Abtin Ghasempour, Rashin Mohseni, Pouya Mahdavi Sharif, Amir Ali Hamidieh","doi":"10.1016/j.cellimm.2024.104898","DOIUrl":"10.1016/j.cellimm.2024.104898","url":null,"abstract":"<div><div>Neuroblastoma (NB) is the most common extracranial solid tumor of childhood forming around 15 % of all pediatric tumors. Despite advances in the treatment of NB, high-risk patients still face a grave prognosis. Adoptive cell therapies based on NK cells are becoming an assistive treatment for such cases. Moreover, there is also evidence that NKT-based therapies have promising results in the management of NB. Lower complications in comparison with adoptive T cell therapies, various cell sources, and miscellaneous tumor recognition mechanisms are some of the advantages of NK- and NKT-based therapies. This review is dedicated to searching for recent advances in this field.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"407 ","pages":"Article 104898"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779482","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}
Pub Date : 2024-12-24DOI: 10.1016/j.cellimm.2024.104913
Jie Fang , Jin Wang , Xinyue Zhao, Yaping Yang, Yujia Xiao
Aims
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.
Main methods
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.
Key findings
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.
Significance
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.
{"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":"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}
Pub Date : 2024-11-14DOI: 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
Ulcerative colitis (UC) is a chronic nonspecific inflammatory bowel disease characterized mainly by inflammatory changes in the intestinal mucosa. While the specific etiology of UC remains unclear, it is generally believed that it is related to many factors, among which the imbalance in the expression of molecules involved in pro-inflammatory and anti-inflammatory processes can lead to UC. CCL5 (C–C chemokine ligand 5) is one of the key pro-inflammatory factors and plays an indispensable role in various inflammatory diseases, including UC. CCL5 binds and activates the receptor CCR5 (C–C chemokine receptor type 5), which in turn, promotes signaling pathways such as PI3K/AKT, NF-κB, and Ras/MAPK, playing an important role in the pathogenesis of UC. The focus of this paper is on the function of the CCL5/CCR5 axis and its subsequent signaling pathways in UC therapy. In addition to this, the article further explores the possible healing benefits of CCR5 antagonists and agonists aimed at the CCL5/CCR5 axis for UC treatment.
{"title":"The CCL5/CCR5 axis in ulcerative colitis","authors":"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","doi":"10.1016/j.cellimm.2024.104891","DOIUrl":"10.1016/j.cellimm.2024.104891","url":null,"abstract":"<div><div>Ulcerative colitis (UC) is a chronic nonspecific inflammatory bowel disease characterized mainly by inflammatory changes in the intestinal mucosa. While the specific etiology of UC remains unclear, it is generally believed that it is related to many factors, among which the imbalance in the expression of molecules involved in pro-inflammatory and anti-inflammatory processes can lead to UC. CCL5 (C–C chemokine ligand 5) is one of the key pro-inflammatory factors and plays an indispensable role in various inflammatory diseases, including UC. CCL5 binds and activates the receptor CCR5 (C–C chemokine receptor type 5), which in turn, promotes signaling pathways such as PI3K/AKT, NF-κB, and Ras/MAPK, playing an important role in the pathogenesis of UC. The focus of this paper is on the function of the CCL5/CCR5 axis and its subsequent signaling pathways in UC therapy. In addition to this, the article further explores the possible healing benefits of CCR5 antagonists and agonists aimed at the CCL5/CCR5 axis for UC treatment.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"407 ","pages":"Article 104891"},"PeriodicalIF":3.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721487","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}
Pub Date : 2024-11-13DOI: 10.1016/j.cellimm.2024.104890
Eva M. Gossink , Paul J. Coffer , Alessandro Cutilli , Caroline A. Lindemans
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.
{"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}
Pub Date : 2024-11-07DOI: 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
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.
{"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}
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