Human CCR6 Full Length Protein (VLP)

Abstract: The cancer-related mortality of primary liver cancer ranks third globally, and hepatocellular carcinoma (HCC) is predominant, posing a serious threat to patients' health. Understanding HCC's pathogenesis and target molecules is crucial for early diagnosis and prognosis. Extracellular vesicles (EVs) and their carried miRNAs impact tumor progression. This study aims to investigate miR-183-5p in HCC cell-derived EVs on angiogenesis, progression, and metastasis, and provide diagnostic and therapeutic evidence.qRT-PCR was used to evaluate the expression of miR-183-5p in HCC tissue and plasma EV samples. Contrast-enhanced ultrasound and The Cancer Genome Atlas evaluated its correlation with angiogenesis and prognosis. In vitro, cell counting kit-8 (CCK-8), colony formation, transwell, tube formation, and permeability assays examined the effect of HCC cell-derived EVs on human umbilical vein endothelial cells (HUVECs). Subcutaneous tumor and lung metastasis models in nude mice verified it in vivo effects. RNA sequencing and databases predicted downstream genes and pathways, and dual luciferase and western blotting assays verified binding and activation. Conditioned medium from treated HUVECs was used on HCC cells, and chemokine levels measured. The CCL20/CCR6 axis effect was studied in vitro and in vivo by knocking down CCR6.This study revealed the abnormal upregulation of miR-183-5p in both tissues and plasma EVs from patients with HCC, and its association with unfavorable prognosis. In vivo experiments, the promoting effects of miR-183-5p in HCC cell-derived EVs on the progression, metastasis and angiogenesis were verified by employing subcutaneous tumor formation models and lung metastasis models in nude mice. We demonstrated that miR-183-5p in HCC cell-derived EVs induced HUVECs proliferation, migration, angiogenesis and permeability by downregulating SIK1 expression and activating the PI3K/AKT signaling pathway in vitro. Moreover, stimulated HUVECs could secrete the chemokine CCL20 and induce HCC progression and metastasis through the CCL20/CCR6 signal pathway in vitro and in vivo.The findings indicated that miR-183-5p delivered by EVs from HCC cells is crucial in mediating the communication between HUVECs and HCC cells by modulating the SIK1/PI3K/AKT and CCL20/CCR6 signaling pathways, and EVs-miR-183-5p might be a potential therapeutic target for HCC patients.Copyright © 2025 Han, Gong, Xing, Zhou, Wang, Xu, Zhou and Xue.

Abstract: To investigate the mechanisms by which Porphyromonas gingivalis (P. gingivalis) promotes the malignant progression of oral squamous cell carcinoma (OSCC) through the recruitment of chemokine receptor 6-positive (CCR6+) regulatory T cells (Treg) in the tumor microenvironment (TME).The Cancer Genome Atlas (TCGA) database was used to analyze the correlation between chemokine ligand 20 (CCL20), CCR6, and Treg. The Treg enrichment index and the expression levels of interleukin (IL)-10 and tumor necrosis factor β1 (TGF-β1) were assessed in the high CCR6 expression group of OSCC patients. C57BL/6 mice were randomly assigned to a control group and an experimental group (n = 6 in each group). The control group received a single injection of 100 μL SCC7, a mice head and neck squamous carcinoma cell line, while the experimental group received a single injection of 100 μL mixture of SCC7 cells and P. gingivalis in the cheek. After two weeks, the mice were sacrificed, and immunohistochemistry was performed to assess the expression levels of CCR6 and forkhead box protein 3 (FOXP3) in OSCC. Flow cytometry was performed to analyze the effects of P. gingivalis on OSCC malignant biological behavior, CCR6+ Treg cells, and the immune microenvironment.Bioinformatics analysis revealed a correlation between CCL20, CCR6, and Treg (r = 0.373, P < 0.000 1). OSCC patients with high CCR6 expression showed higher Treg enrichment scores and increased IL-10 expression. Animal experiments showed that P. gingivalis promoted the increase in the tumor volume (mm3) (0.294 ± 0.105 in the control group and 0.526 ± 0.101 in the experimental group, P < 0.01) and mass (mg) (206.200 ± 53.950 in the control group and 376.000 ± 119.200 in the experimental group, P < 0.01) in mice with OSCC. Immunohistochemistry confirmed a correlation between CCR6 and FOXP3 (r = 0.659, P < 0.05), and P. gingivalis promoted the expression of CCR6 and FOXP3. Flow cytometry analysis showed that P. gingivalis increased the proportion of CCR6+ Treg (%) (13.780 ± 1.506 in the control group and 18.260 ± 2.257 in the experimental group, P < 0.01) and decreased the proportion of CD8+ T cells (%) (27.120 ± 1.647 in the control group and 21.060 ± 3.148 in the experimental group, P < 0.01) in OSCC, thereby promoting the formation of a immunosuppressive microenvironment.P. gingivalis promotes the malignant progression of OSCC by recruiting CCR6+ Treg cells to form an immunosuppressive TME.© 2025《四川大学学报（医学版）》编辑部 Copyright ©2025 Editorial Office of Journal of Sichuan University (Medical Sciences).

Abstract: Mortality rates for hepatocellular carcinoma (HCC) remain high, while multimodal treatment approaches offer new perspectives. Here, we investigated the association of extracellular nicotinamide adenine dinucleotide (eNAD+) on ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (CD203a, ENPP1 or PC-1) on Th17 cells in relation to the likelihood of HCC recurrence following liver resection.The study compared heparinized blood plasma samples from 95 patients who underwent liver resection, including 25 patients with HCC and 24 control patients without liver disease. Plasma eNAD+ concentrations were determined using a heat-based dichotomous pH extraction method, followed by enzymatic cycling and a colorimetric assay for quantification. Fibrosis was graded histologically using the Desmet score (F0-F4). Surface expression analysis was performed using flow cytometry.With increasing grades of liver fibrosis predominant in HCC patients, a significant reduction in plasma eNAD+ concentrations was measured (p < 0.05). Further, a significant correlation was found between HCC patients and CD203a expression on CD4+, CCR4+ as well as CCR6+ T cells (p < 0.05). Patients who exhibited high proportions of CD203a expressing Th17 cells (CD4+, CCR6+ CCR4+) post surgery were found to be at a sixfold increased risk (HR 6.38, 95% Cl 1.51-27.00) of HCC recurrence and had a median recurrence-free survival of 233 days (p < 0.05), compared to patients with low CD203a expressing Th17 cells (CD4+ CCR6+ CCR4+). Similarly, patients who had a high proportion of CD203a expressing Th17 cells (CD4+ CCR6+) following surgery had a fivefold increased risk (HR 5.56, 95% Cl 1.58-19.59) of HCC recurrence and a median recurrence-free survival of 334 days (p < 0.05) compared to those with low CD203a expressing Th17 cells (CCR6+).The data indicates that eNAD+ levels are decreased in patients with liver fibrosis or cirrhosis. Strikingly, patients with high CD203a expression on Th17 cells had a significantly increased likelihood of recurrence, highlighting its potential as a valuable prognostic marker and a possible therapeutic target.© 2025. The Author(s).

Abstract: Rheumatoid arthritis (RA) is a systemic autoimmune disease currently with no universally highly effective prevention strategies. Identifying pathogenic immune phenotypes in at-risk populations prior to clinical onset is crucial to establishing effective prevention strategies. Here, we applied multimodal single-cell technologies (mass cytometry and CITE-Seq) to characterize the immunophenotypes in blood from at-risk individuals (ARIs) identified through the presence of serum antibodies against citrullinated protein antigens (ACPAs) and/or first-degree relative (FDR) status, as compared with patients with established RA and people in a healthy control group. We identified significant cell expansions in ARIs compared with controls, including CCR2+CD4+ T cells, T peripheral helper (Tph) cells, type 1 T helper cells, and CXCR5+CD8+ T cells. We also found that CD15+ classical monocytes were specifically expanded in ACPA-negative FDRs, and an activated PAX5lo naive B cell population was expanded in ACPA-positive FDRs. Further, we uncovered the molecular phenotype of the CCR2+CD4+ T cells, expressing high levels of Th17- and Th22-related signature transcripts including CCR6, IL23R, KLRB1, CD96, and IL22. Our integrated study provides a promising approach to identify targets to improve prevention strategy development for RA.