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A large number of cancer patients relapse after chemotherapeutic treatment. The immune system is capable of identifying and destroying cancer cells, so recent studies have highlighted the growing importance of using combinatorial chemotherapy and immunotherapy. However, many patients have innate or acquired resistance to immunotherapies. Long-term follow-up in a pooled meta-analysis exhibited long-term survival in approximately 20% of patients treated with immune checkpoint inhibitors or the adoptive transfer of chimeric T cells. It has been reported that high levels of immunoregulatory cells in cancer patients contribute to immunotherapy resistance via immunosuppression. Among the most important regulatory cell subtypes are the CD4+ T-regulatory cells (Tregs), identified by their expression of the well-characterized, lineage-specific transcription factor FOXP3. In addition to CD4+ Tregs, other regulatory cells present in the tumor microenvironment, namely CD8+ Tregs and IL10-producing B-regulatory cells (Bregs) that also modulate the immune response in solid and lymphoid tumors. These cells together have detrimental effects on tumor immune surveillance and anti-tumor immunity. Therefore, targeting these regulatory lymphocytes will be crucial in improving treatment outcomes for immunotherapy.
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Linfocitos T Reguladores , Inmunoterapia , Neoplasias , Terapia de InmunosupresiónRESUMEN
Xenotransplantation is the most promising method to resolve the organ shortage problem in the future. In recent years, the advances in gene editing and immunological technique have driven the rapid development of xenotransplantation. However, there are still many insurmountable obstacles in the clinical application of xenotransplantation, among which the rejection is the most important cause of the xenotransplantation failure. Regulatory immunological cells are a group of immunological cells with the negative regulation function in the body, which can inhibit allotransplantation rejection and prolong the survival time of the graft. This paper summarized the research progress of regulatory immunological cells in the xenotransplantation application in recent years, providing reference for the prevention and treatment of xenotransplantation rejection.
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Objective:To explore the characteristics of B cell subsets in rheumatoid arthritis (RA) patients and the regulation of epigallocatechingallate (EGCG) on B cell subsets in RA patients. Methods:Twenty-nine age- and sex-matched RA patients and 29 healthy controls were selected, and the difference of B cell subsets in peripheral blood between the two groups was analyzed by paired t-test. According to the value of disease activity score in 28 joints (DAS28), RA patients were divided into active group (2.6 ≤ DAS28 0.05). There was no significant difference in the numbers and the proportions of total B cells and B cell subsets (except CD19+ IL-10+ Breg) between 10 RA patients of active group and 19 RA patients of highly active group (P>0.05). There was no significant difference in the number and the proportion of CD19+ IL-10+ Breg in lymphocytes between 6 RA patients of active group and 12 RA patients of highly active group (P>0.05). The proportion of total B cells was weakly positively correlated with IgG type rheumatoid factor (r=0.308). EGCG could significantly increase the proportion of CD19+ IL-10+ Breg (P0.05). Conclusion:B cells may play an auxiliary role in the development of RA. The number of CD19+ IL-10+ Breg in RA patients increases as a feedback. EGCG can promote Breg proliferation and suppress BAFF-R mRNA expression.
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Objectives The aim of the study was to detect the frequency of B regulatory cells (Breg)and the correlation between Breg and T regulatory cells (Treg) in pancreatic cancer patients,and to investigate its role in pathogenesis of pancreatic cancer.Methods 50 pancreatic cancer patients and 21 healthy controls were enrolled.CD19+CD24hiCD38hi Breg and CD4+CD25high Treg was also determined via flow cytometry.The correlation between Breg and Treg was analyzed by Spearman correlation test.Results Upregulation of CD19+CD24hiCD381hi Breg was associated with pancreatic cancer progression.Furthermore,this B cell subset was positively correlated with the frequency of CD4 + CD25high Treg cells.Conclusions Together,CD19 + CD24hiCD38hi Breg cells are significantly elevated in pancreatic cancer patients,indicating this B cell subset might play an vital role in clinical progression of pancreatic cancer.The significant positive correlation between Breg and Treg may suggest CD 1TCD24hiCD38hi Breg are affecting tumor progression through Treg cells.
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Objective To ascertain whether estrogen could induce B cell to produce interleukin(IL)-10. Methods C57BL/6 splenic B cells were purified by magnetic activated cell sorting(MACS)method,followed by estrogen treatment for 3 days. The secretion of IL-10 from cultured cell supernatant was tested by ELISA technique. The abundance of mRNA for IL-10、PD-L1 and RBM47 in B cells with estrogen treatment was tested by real-time PCR method. The intracellular IL-10 expression and the surface PD-L1 expression of treated B cells were tested by fluorescence activated cell sorting(FACS)method. And the expression of RBM47 in B cells by estrogen treatment was tested using Western blotting method. Results Estrogen could induce B cell to produce IL-10 in a dose-dependent manner. Estrogen treatment could increase the percentage of IL-10+B cells,the abundance of mRNA for IL-10,PD-L1 and RBM47 in B cells,as well as the expression of PD-L1 on B cell surface. Furthermore,our experimental result indicated the upreg?ulation of RBM47 expression in B cells by estrogen treatment. Conclusion Estrogen treatment in vitro can induce the upregulation of IL-10+regulatory B cells(Breg). Upregulation of RBM47 in the treated B cells might participate in this process by stabilizing IL-10 mRNA.
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Objective To explore the effect and mechanism of estrogen in mouse model with experimental autoimmune encephalomyelitis (EAE). Methods A mouse model with EAE was induced in female C57BL/6J mice by immunizing with MOG35-55 and CFA. The immunized mice were randomly divided into two groups. In treatment group, estrogen at 50 μmol/L was injected into mice by s.c. in a consecutive fashion from the day of myelin oligodendroglia glycoprotein (MOG) immunization until the day of experiment completion. Meanwhile, in control group, solvent was injected into mice by the same means. The disease score for EAE was recorded everyday. The secretion of TNF-α and IL-17A from cultured mouse splenic cell supernatant was tested by ELISA technique. The abundance of mRNA for TNF-α, IL-17A, PD-1 and PD-L1 in spinal cord was tested by real-time PCR method. The intracellular expression for TNF-α and IL-17A and the surface expression for CD4/PD-1, CD19/PD-L1, CD4/CD25/Foxp3, CD19/CD21/CD23 as well as CD19/ CD5/CD1dhigh of mouse splenocytes were tested by fluorescence activated cell sorting (FACS) method. Results The prophylactic treatment of estrogen could delay the progress in mouse EAE. Histopathological evaluation of mouse spinal cord specimen showed reduced demyelination and inflammatory cell invasion by estrogen treatment. Furthermore, both TNF-α and IL-17A production in estrogen treated mice was significantly downregulated compared to those in control group mice. However, the transcription and expression level for PD-1 in CD4+T cells and that for PD-L1 in CD19+B cells were observed to be upregulated in estrogen treated mice. Also, the percentages of CD19+CD21highCD23low and CD19+CD5+CD1dhigh Breg cells in splenocytes were augmented by estrogen treatment. In contrast, no changes were observed for the proportion of the splenic CD4+CD25+Foxp3+Tregs in mice composed to estrogen treatment with comparison to those in mice with vehicle treatment. Conclusion The prophylactic treatment of estrogen can delay the disease progress in EAE mice, likely through the upregulation of PD-1/PD-L1 pathway and Breg cells.
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Objective To ascertain whether estrogen could induce B cell to produce interleukin (IL) -10. Methods C57BL/ 6 splenic B cells were purified by magnetic activated cell sorting (MACS) method, followed by estrogen treatment for 3 days. The secretion of IL- 10 from cultured cell supernatant was tested by ELISA technique. The abundance of mRNA for IL- 10, PD- L1 and RBM47 in B cells with estrogen treatment was tested by real-time PCR method. The intracellular IL-10 expression and the surface PD-L1 expression of treated B cells were tested by fluorescence activated cell sorting (FACS) method. And the expression of RBM47 in B cells by estrogen treatment was tested using Western blotting method. Results Estrogen could induce B cell to produce IL- 10 in a dose-dependent manner. Estrogen treatment could increase the percentage of IL-10+ B cells, the abundance of mRNA for IL-10, PD-L1 and RBM47 in B cells, as well as the expression of PD-L1 on B cell surface. Furthermore, our experimental result indicated the upregulation of RBM47 expression in B cells by estrogen treatment. Conclusion Estrogen treatment in vitro can induce the upregulation of IL- 10+ regulatory B cells (Breg). Upregulation of RBM47 in the treated B cells might participate in this process by stabilizing IL- 10 mRNA.
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Foxp3 is a transcript factor for regulatory T cell development. Interestingly, Foxp3-expressing cells were identified in B cells, especially in CD19(+)CD5(+) B cells, while those were not examined in CD19(+)CD5(-) B cells. Foxp3-expressing CD5(+) B cells in this study were identified in human PBMCs and were found to consist of 8.5+/-3.5% of CD19(+)CD5(+) B cells. CD19(+)CD5(+)Foxp3(+) B cells showed spontaneous apoptosis. Rare CD19(+)CD5(+) Foxp3(+) regulatory B cell (Breg) population was unveiled in human peripheral blood mononuclear cells and suggested as possible regulatory B cells (Breg) as regulatory T cells (Treg). The immunologic and the clinical relevant of Breg needs to be further investigated.