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1.
Journal of Experimental Hematology ; (6): 297-300, 2023.
Article in Chinese | WPRIM | ID: wpr-971140

ABSTRACT

The multiple myeloma (MM), the second most common hematologic malignancy, is malignant proliferative disease of plasma cells. Although the application of many targeted drugs has significantly prolonged the survival time of MM patients, it is still an incurable disease. In recent years, the immunosuppression caused by interaction between tumor microenvironment(TME) and tumor cells has attracted people's attention gradually. As a kind of immunosuppressive cells in TME, regulatory T cells (Treg) play an important role in the progress of MM. Treg is related to the proliferation and metastasis of tumors, and can lead to the progress of MM by promoting the angiogenesis and generating immunosuppressive TME. In this review, we briefly summarized the latest research progress on the impact of Treg on the pathogenesis of MM.


Subject(s)
Humans , Multiple Myeloma/pathology , T-Lymphocytes, Regulatory/pathology , Immune Tolerance , Plasma Cells/pathology , Immunosuppression Therapy , Tumor Microenvironment
2.
Journal of Southern Medical University ; (12): 280-286, 2023.
Article in Chinese | WPRIM | ID: wpr-971526

ABSTRACT

OBJECTIVE@#To investigate the changes in percentage of GATA3+ regulatory T (Treg) cells in patients with allergic rhinitis (AR) and mouse models.@*METHODS@#The nasal mucosa specimens were obtained from 6 AR patients and 6 control patients for detection of nasal mucosal inflammation. Peripheral blood mononuclear cells (PBMC) were collected from 12 AP patients and 12 control patients to determine the percentages of Treg cells and GATA3+ Treg cells. In a C57BL/6 mouse model of AR, the AR symptom score, peripheral blood OVA-sIgE level, and nasal mucosal inflammation were assessed, and the spleen of mice was collected for detecting the percentages of Treg cells and GATA3+ Treg cells and the expressions of Th2 cytokines.@*RESULTS@#Compared with the control patients, AR patients showed significantly increased eosinophil infiltration and goblet cell proliferation in the nasal mucosa (P < 0.01) and decreased percentages of Treg cells and GATA3+ Treg cells (P < 0.05). The mouse models of AR also had more obvious allergic symptoms, significantly increased OVA-sIgE level in peripheral blood, eosinophil infiltration and goblet cell hyperplasia (P < 0.01), markedly lowered percentages of Treg cells and GATA3+ Treg cells in the spleen (P < 0.01), and increased expressions of IL-4, IL-6 and IL-10 (P < 0.05).@*CONCLUSION@#The percentage of GATA3+ Treg cells is decreased in AR patients and mouse models. GATA3+ Treg cells possibly participate in Th2 cell immune response, both of which are involved in the occurrence and progression of AR, suggesting the potential of GATA3+ Treg cells as a new therapeutic target for AR.


Subject(s)
Animals , Mice , Humans , Cytokines/metabolism , Disease Models, Animal , GATA3 Transcription Factor , Inflammation , Leukocytes, Mononuclear/metabolism , Mice, Inbred BALB C , Mice, Inbred C57BL , Nasal Mucosa/metabolism , Ovalbumin , Rhinitis, Allergic/therapy , T-Lymphocytes, Regulatory , Th2 Cells/metabolism
3.
Chinese Journal of Otorhinolaryngology Head and Neck Surgery ; (12): 225-232, 2023.
Article in Chinese | WPRIM | ID: wpr-971438

ABSTRACT

Objective: To investigate the role of CD4+CD25+regulatory cell (CD4+CD25+Treg) in auditory neuropathy (AN) using a rat model of autoimmune auditory neuropathy. Methods: The SD rats were immunized with P0 protein emulsified in complete Freunds adjuvant for 8 weeks. The number of CD4+CD25+Treg in peripheral blood and cochlea and the expression of Foxp3 gene in cochlea were detected respectively 2, 4, 6 and 8 weeks after the immunization with P0 protein in rats. Then CD4+CD25+Treg were transferred intravenously to the AN rats at 2, 4, 6 and 8 weeks of the immunization, respectively. The change of auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) were detected, and the morphological changes in the inner ear were investigated. Results: The number of CD4+CD25+Treg in the peripheral blood of AN rats decreased gradually after 2, 4, 6 and 8 weeks of P0 protein immunization. The number of CD4+CD25+Treg in cochlea gradually increased with the prolongation of immunization time, but the expression of Foxp3 gene in cochlea gradually decreased over time. After intravenous transplantation of CD4+CD25+Treg in AN rats, the threshold of ABR response decreased, and DPOAE had no significant change. The number of spiral ganglion neurons in cochlea increased, and hair cells had no significant change under electron microscope. Conclusions: The decrease in the number and function of CD4+CD25+Treg reduces its inhibitory effect on autoimmune response and promotes the occurrence of autoimmune auditory neuropathy in AN rats. Adoptive transfer of CD4+CD25+Treg can reduce the autoimmune response and promote the recovery of autoimmune auditory neuropathy.


Subject(s)
Animals , Rats , Forkhead Transcription Factors , Myelin P0 Protein , Rats, Sprague-Dawley , T-Lymphocytes, Regulatory , CD4 Antigens/immunology , Interleukin-2 Receptor alpha Subunit/immunology
4.
Journal of Clinical Otorhinolaryngology Head and Neck Surgery ; (12): 272-277, 2023.
Article in Chinese | WPRIM | ID: wpr-982731

ABSTRACT

Objective:To prepare PLGA nanoparticles loaded with Der f 1/IGF-1(Der f 1/IGF-1 NPs) and investigate their role in promoting the formation of Treg cells. Methods:NPs coated with Der f 1/IGF-1 were prepared by double emulsion method and their physicochemical properties and cumulative release rate in vitro were analyzed. After pretreatment, BMDC was divided into Saline group, Blank NPs group, Der f 1/IGF-1 group and Der f 1/IGF-1 NPs group. Determination of the expression of IL-10 and TGF-β in BMDC by ELISA. The number of Treg cells was detected by flow cytometry. Results:The results showed that Der f 1/IGF-1 NPs were spherical structures, with good dispersion, particle size less than 200 nm, negative charge and stable slow-release effect of Zeta potential. After BMDC pretreatment, the expression levels of TGF-β and IL-10 in BMDC cells in the Der f 1/IGF-1 NPs group were significantly increased compared with the Blank NPs group, and the difference was statistically significant(P<0.001). After co-culture with CD4+ T cells, the proportion of Treg cells produced in the Der f 1/IGF-1 NPs group was significantly increased, and the difference was statistically significant(P<0.001). Conclusion:Der f 1/IGF-1 NPs can induce Treg cell generation in vitro. This study provides a new and more effective method for the reconstruction of immune tolerance dysfunction.


Subject(s)
Humans , T-Lymphocytes, Regulatory/metabolism , Interleukin-10/metabolism , Insulin-Like Growth Factor I , Transforming Growth Factor beta , Nanoparticles/chemistry , Particle Size , Drug Carriers/chemistry
5.
Chinese Critical Care Medicine ; (12): 586-591, 2023.
Article in Chinese | WPRIM | ID: wpr-982637

ABSTRACT

OBJECTIVE@#To investigate the effect of circulating exosomes (EXO) on T cell function in patients with sepsis.@*METHODS@#Plasma EXO were obtained by ultracentrifugation from 10 patients with sepsis admitted to the emergency intensive care unit of Guangdong Provincial People's Hospital Affiliated to Southern Medical University. Transmission electron microscopy observation, nanoparticle tracking analysis (NTA), and Western blotting were used to detect EXO markers to identify their characteristics. Furthermore, peripheral blood mononuclear cells (PBMC) were isolated from the peripheral blood of 5 healthy volunteers, primary T cells were sorted by magnetic beads and expanded in vitro. After 24 hours of intervention with different doses (0, 1, 2.5, 5, 10 mg/L) of circulating EXO in patients with sepsis, T-cell activity was assessed using a cell counting kit-8 (CCK-8). The expression of T cell activation indicators CD69 and CD25 were observed using flow cytometry. Additional evaluations were performed on immunosuppressive indicators including the expression of programmed cell death 1 (PD-1) in CD4+ T cells and the proportion of regulatory T cell (Treg).@*RESULTS@#The identification results confirmed that the successful isolation of EXO from the plasma of sepsis patients. The expression level of circulating EXO in sepsis patients was higher than that in healthy control group (mg/L: 48.78±5.14 vs. 22.18±2.25, P < 0.01). After 24 hours of intervention with 5 mg/L of plasma EXO from sepsis patients, T cells activity began to show suppression [(85.84±0.56)% vs. (100.00±0.00)%, P < 0.05]. As the dosage increased, after 24 hours of intervention with 10 mg/L of EXO, T cells activity was significantly suppressed [(72.44±2.36)% vs. (100.00±0.00)%, P < 0.01]. Compared with the healthy control group, after T cells intervention with plasma EXO from sepsis patients, the expression of early activation marker CD69 was significantly reduced [(52.87±1.29)% vs. (67.13±3.56)%, P < 0.05]. Meanwhile, there was an upregulation of PD-1 expression in T cells [(57.73±3.06)% vs. (32.07±0.22)%, P < 0.01] and an increase in the proportion of Treg [(54.67±1.19)% vs. (24.60±3.51)%, P < 0.01]. However, the expression of the late activation marker CD25 remained stable [(84.77±3.44)% vs. (85.93±2.32)%, P > 0.05].@*CONCLUSIONS@#Circulating EXO in sepsis patients induce T cell dysfunction, which may be a novel mechanism lead to immunosuppression in sepsis.


Subject(s)
Humans , Leukocytes, Mononuclear , Exosomes/metabolism , Programmed Cell Death 1 Receptor/metabolism , T-Lymphocytes, Regulatory/metabolism , Sepsis/metabolism
6.
Chinese Critical Care Medicine ; (12): 518-523, 2023.
Article in Chinese | WPRIM | ID: wpr-982625

ABSTRACT

OBJECTIVE@#To investigate the mechanism of regulatory T cells (Treg) in heat stroke (HS)-induced acute kidney injury (AKI).@*METHODS@#Male SPF Balb/c mice were randomly divided into control group, HS group (HS+Rat IgG), HS+PC61 group, and HS+Treg group (n = 6). The HS mice model was established by making the body temperature of the mice reach 42.7 centigrade at room temperature 39.5 centigrade with relative humidity 60% for 1 hour. In HS+PC61 group, 100 μg PC61 antibody (anti-CD25) was injected through the tail vein in consecutive 2 days before the model was established to eliminate Tregs. Mice in HS+Treg group was injected with 1×106 Treg via tail vein immediately after successful modeling. The proportion of Treg infiltrated in the kidney, serum creatinine (SCr) and histopathology, levels of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) both in the serum and kidney tissue, as well as proportion of neutrophils and macrophages located in the kidney were observed at 24 hours after HS.@*RESULTS@#HS dampened renal function and exaggerated kidney injury, up-regulated levels of inflammatory cytokines both in local kidney and circulation, and increased infiltration of neutrophils and macrophages to the injured kidneys. The proportion of Treg (Treg/CD4+) infiltrated in kidney was significantly decreased in HS group, compared with control group [(3.40±0.46)% vs. (7.67±0.82)%, P < 0.01]. Compared with HS group, local Tregs in kidney were almost completely depleted via PC61 antibody [(0.77±0.12)% vs. (3.40±0.46)%, P < 0.01]. Depletion of Tregs could exacerbate HS-AKI, indicating by increased serum creatinine [SCr (mmol/L): 348.22±35.36 vs. 254.42±27.40, P < 0.01] and pathological injury (Paller score: 4.70±0.20 vs. 3.60±0.20, P < 0.01), incremental levels of IFN-γand TNF-α both in injured kidney and serum [serum IFN-γ (ng/L): 747.70±64.52 vs. 508.46±44.79, serum TNF-α (ng/L): 647.41±26.62 vs. 464.53±41.80, both P < 0.01], and more infiltrated neutrophils and macrophages in the injured kidney [neutrophil proportion: (6.63±0.67)% vs. (4.37±0.43)%, macrophage proportion: (38.70±1.66)% vs. (33.19±1.55)%, both P < 0.01]. On the contrast, adoptive transfer of Tregs could reverse the aforementioned effects of Treg depletion, indicating by incremental proportion of Tregs in the injured kidney [(10.58±1.19)% vs. (3.40±0.46)%, P < 0.01], decreased serum creatinine [SCr (mmol/L): 168.24±40.56 vs. 254.42±27.40, P < 0.01] and pathological injury (Paller score: 2.73±0.11 vs. 3.60±0.20, P < 0.01), reduced levels of IFN-γ and TNF-α both in injured kidney and serum [serum IFN-γ (ng/L): 262.62±22.68 vs. 508.46±44.79, serum TNF-α (ng/L): 206.41±22.58 vs. 464.53±41.80, both P < 0.01], and less infiltrated neutrophils and macrophages in the injured kidney [neutrophil proportion: (3.04±0.33)% vs. (4.37±0.43)%, macrophage proportion: (25.68±1.93)% vs. (33.19±1.55)%, both P < 0.01].@*CONCLUSIONS@#Treg might be involved in HS-AKI, possibly via down-regulation of pro-inflammatory cytokines and infiltration of inflammatory cells.


Subject(s)
Male , Animals , Mice , Rats , T-Lymphocytes, Regulatory , Creatinine , Tumor Necrosis Factor-alpha , Heat Stroke , Acute Kidney Injury , Cytokines , Interferon-gamma
7.
Journal of Zhejiang University. Science. B ; (12): 312-325, 2023.
Article in English | WPRIM | ID: wpr-982370

ABSTRACT

Spinal cord injury (SCI) causes motor, sensory, and autonomic dysfunctions. The gut microbiome has an important role in SCI, while short-chain fatty acids (SCFAs) are one of the main bioactive mediators of microbiota. In the present study, we explored the effects of oral administration of exogenous SCFAs on the recovery of locomotor function and tissue repair in SCI. Allen's method was utilized to establish an SCI model in Sprague-Dawley (SD) rats. The animals received water containing a mixture of 150 mmol/L SCFAs after SCI. After 21 d of treatment, the Basso, Beattie, and Bresnahan (BBB) score increased, the regularity index improved, and the base of support (BOS) value declined. Spinal cord tissue inflammatory infiltration was alleviated, the spinal cord necrosis cavity was reduced, and the numbers of motor neurons and Nissl bodies were elevated. Enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction (qPCR), and immunohistochemistry assay revealed that the expression of interleukin (IL)‍-10 increased and that of IL-17 decreased in the spinal cord. SCFAs promoted gut homeostasis, induced intestinal T cells to shift toward an anti-inflammatory phenotype, and promoted regulatory T (Treg) cells to secrete IL-10, affecting Treg cells and IL-17+ γδ T cells in the spinal cord. Furthermore, we observed that Treg cells migrated from the gut to the spinal cord region after SCI. The above findings confirm that SCFAs can regulate Treg cells in the gut and affect the balance of Treg and IL-17+ γδ T cells in the spinal cord, which inhibits the inflammatory response and promotes the motor function in SCI rats. Our findings suggest that there is a relationship among gut, spinal cord, and immune cells, and the "gut-spinal cord-immune" axis may be one of the mechanisms regulating neural repair after SCI.


Subject(s)
Animals , Rats , Interleukin-17 , Rats, Sprague-Dawley , Recovery of Function , Spinal Cord Injuries/drug therapy , T-Lymphocytes, Regulatory , Receptors, Antigen, T-Cell, gamma-delta/immunology
8.
Journal of Experimental Hematology ; (6): 666-670, 2023.
Article in Chinese | WPRIM | ID: wpr-982114

ABSTRACT

OBJECTIVE@#To investigate the expression and significance of regulatory T cells (Tregs), FoxP3 and transforming growth factor-β (TGF-β) in different phase of chronic myeloid leukemia (CML).@*METHODS@#Peripheral blood of 73 CML patients in Department of Hematology, Heze Municipal Hospital from March 2018 to March 2021 were collected. According to patient's period in CML, they were divided into ND CML group (newly diagnosed), CP CML group (chronic period), and BP CML group (blast phase). The percentage of Tregs, expression level of FoxP3 mRNA and TGF-β were detected by flow cytometry, RT-qPCR, and ELISA, respecitively. The roles of above indices in clinical pathogenesis of patients with CML were analyzed.@*RESULTS@#The proportion of Treg in the ND CML group was slightly higher than the CP CML group, but the difference was not statistically significant (P =0.695), while the BP CML group was significantly higher than the other two groups (P =0.008, P <0.001). The expression levels of FoxP3 mRNA in ND CML group, CP CML group and BP CML group were 11.61±2.21, 6.46±1.35 and 8.54±2.13, respectively. Significant difference in FoxP3 mRNA levels was observed among patients in different phases of CML (F =55.199, P <0.001). The expression levels of FoxP3 mRNA both in ND CML group and BP CML group were significantly higher than that in CP CML group (P <0.001), and the ND CML group was the highest (P <0.001). However, the expression levels of TGF-β in different phases of CML showed no statistical differences (H =0.634, P =0.728).@*CONCLUSION@#The abnormal distribution of Treg subset in different phases of CML and the significant increase of the expression level of FoxP3 mRNA in the new onset and blast phase of CML suggest that Tregs may promote the occurrence and progression of CML through immune regulation.


Subject(s)
Humans , Blast Crisis/metabolism , Forkhead Transcription Factors/metabolism , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , RNA, Messenger/metabolism , T-Lymphocytes, Regulatory/metabolism , Transforming Growth Factor beta/metabolism
9.
Chinese Journal of Schistosomiasis Control ; (6): 277-285, 2022.
Article in Chinese | WPRIM | ID: wpr-940948

ABSTRACT

OBJECTIVE@#To investigate the serum microRNA (miRNA) expression and examine the impact of miRNA expression profiles on T helper type 17 (Th17)/regulatory T cells (Treg) imbalance among patients with cystic echinococcosis, so as to provide insights into the illustration of the mechanisms underlying chronic Echinococcus granulosus infections, and long-term pathogenesis.@*METHODS@#Total RNA was extracted from the sera of cystic echinococcosis patients and healthy controls, and subjected to high-throughput sequencing with the Illumina sequencing platform. Known miRNAs were annotated and new miRNAs were predicted using the miRBase database and the miRDeep2 tool, and differentially expressed miRNAs were identified. The target genes of differentially expressed miRNAs were predicted using the software miRanda and TargetScan, and the intersection was selected for Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Among the differentially expressed miRNAs with the 20 highest fold changes, miRNAs that targeted genes relating to key transcription factors RORC and FOXP3 that determine the production of Th17 and Treg cells or their important regulatory pathways (PI3K-Akt and mTOR pathways) were matched.@*RESULTS@#A total of 53 differentially expressed miRNAs were screened in sera of cystic echinococcosis patients and healthy controls, including 47 up-regulated miRNAs and 6 down-regulated miRNAs. GO enrichment analysis showed that these differentially expressed miRNA were involved DNA transcription and translation, cell components, cell morphology, neurodevelopment and metabolic decomposition, and KEGG pathway analysis showed that the differentially expressed miRNA were mainly involved in MAPK, PI3K-Akt and mTOR signaling pathways. Among the differentially expressed miRNAs with the 20 highest fold changes, there were 3 miRNAs that had a potential for target regulation of RORC, and 15 miRNAs that had a potential to target the PI3K-Akt and mTOR signaling pathways.@*CONCLUSIONS@#Significant changes are found in serum miRNA expression profiles among patients with E. granulosus infections, and differentially expressed miRNAs may lead to Th17/Treg imbalance through targeting the key transcription factors of Th17/Treg or PI3K-Akt and mTOR pathways, which facilitates the long-term parasitism of E. granulosus in hosts and causes a chronic disease.


Subject(s)
Humans , Echinococcosis/genetics , Gene Expression Profiling , MicroRNAs/metabolism , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins c-akt/genetics , T-Lymphocytes, Regulatory , TOR Serine-Threonine Kinases/genetics , Th17 Cells , Transcription Factors/genetics
10.
Chinese Journal of Contemporary Pediatrics ; (12): 411-416, 2022.
Article in Chinese | WPRIM | ID: wpr-928623

ABSTRACT

OBJECTIVES@#To study the expression level of plasma miR-106b-5p in primary immune thrombocytopenia (ITP) and its correlation with the levels of T helper 17 cell (Th17) and regulatory T cell (Treg) and the Th17/Treg ratio.@*METHODS@#A total of 79 children with ITP (ITP group) and 40 healthy children (control group) were selected as subjects. According to the treatment response, the 79 children with ITP were divided into three groups: complete response (n=40), partial response (n=18), and non-response (n=21). Quantitative real-time PCR was used to measure the expression level of miR-106b-5p. Flow cytometry was used to measure the frequencies of Th17 and Treg, and the Th17/Treg ratio was calculated. The correlation of the expression level of plasma miR-106b-5p with the frequencies of Th17 and Treg and the Th17/Treg ratio was analyzed.@*RESULTS@#Compared with the control group, the ITP group had significantly higher levels of miR-106b-5p, Th17, and Th17/Treg ratio (P<0.05) and a significantly lower level of Treg (P<0.05). After treatment, the ITP group had significant reductions in the levels of miR-106b-5p, Th17, and Th17/Treg ratio (P<0.05) and a significant increase in the level of Treg (P<0.05). Compared with the partial response and non-response groups, the complete response group had significantly lower levels of miR-106b-5p, Th17, and Th17/Treg ratio (P<0.05) and a significantly higher level of Treg (P<0.05). The correlation analysis showed that in the children with ITP, the expression level of plasma miR-106b-5p was positively correlated with the Th17 level and the Th17/Treg ratio (r=0.730 and 0.816 respectively; P<0.001) and was negatively correlated with the Treg level (r=-0.774, P<0.001).@*CONCLUSIONS@#A higher expression level of miR-106b-5p and Th17/Treg imbalance may be observed in children with ITP. The measurement of miR-106b-5p, Th17, Treg, and Th17/Treg ratio during treatment may be useful to the evaluation of treatment outcome in children with ITP.


Subject(s)
Child , Humans , Lymphocyte Count , MicroRNAs/genetics , Purpura, Thrombocytopenic, Idiopathic/genetics , T-Lymphocytes, Regulatory , Th17 Cells
11.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 185-193, 2022.
Article in English | WPRIM | ID: wpr-929250

ABSTRACT

To explore the effectiveness and safety of a Chinese medicinal decoction Wuwei Xiaodu Drink (WWXDD) in inhibiting chronic osteomyelitis via regulatory T cells signaling. The effective constitutes of WWXDD and osteomyelitis related genes were screened. Target proteins were cross-validated using the Venny database. GO function and KEGG pathway analysis were performed for target proteins, while pharmacological network was constructed. The bone properties were analyzed by HE staining and the concentrations of immune factors were measured by ELISA. The expression of CTLA-4 and Foxp3 mRNA and STAT5, p-STAT5, CTLA-4 and Foxp3 protein were detected using Real-time PCR and Western blot, respectively. FACS was used to analyze the percentages of cells. A total of 117 genes overlapped between 785 target genes of the active compounds of WWXDD and 912 osteomyelitis related genes. Inflammation-related genes, including IL-6, TNFα, IL-1β and IL-2 showed high connection degree in the drug-compound-disease-target network. GO function and KEGG pathway analysis revealed that 117 intersection genes mainly enriched in virus infection related pathways, immune related pathways and chemokine signaling pathway. Furthermore, the development of chronic osteomyelitis was suppressed in model rats after treatment with WWXDD. Meanwhile, the concentrations of IL-2 and CD4+CD25+Foxp3 Treg percentages together with the levels of p-STAT5, CTLA-4 and Foxp3 were also down-regulated. Furthermore, IL-2 and WWXDD drug-containing serum exhibited opposite effects on regulating IL-2, IL-10, TGF-β1, Foxp3, CTLA4 and STAT5. In addition, a STAT5 phosphorylation inhibitor suppressed the expression of Foxp3 and CTLA-4. WWXDD can treat chronic osteomyelitis through suppressing the main regulating factors of Tregs and interfere its immunodepression. Our results bring a new solution for chronic osteomyelitis.


Subject(s)
Animals , Rats , Forkhead Transcription Factors/metabolism , Interleukin-2/metabolism , Osteomyelitis/metabolism , STAT5 Transcription Factor/metabolism , Signal Transduction , T-Lymphocytes, Regulatory
12.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 102-110, 2022.
Article in English | WPRIM | ID: wpr-929240

ABSTRACT

The infiltration of immune cells into the hepatocellular carcinoma microenvironment is the main reason why hepatocellular carcinoma patients are prone to carcinoma recurrence and the disease are incurable. Notably, the infiltration of Treg cells is the main trigger. Dahuang Zhechong pill (DHZCP) is a traditional Chinese herbal compound successful in the treatment of hepatitis and hepatocellular carcinoma. DHZCP can heal and nourish while slowing the onset of the disease, thereby strengthening the body's immune function. It can localize tumors and ultimately achieve the goal of eliminating tumors. In this study, an orthotopic liver cancer model of mice was used to explore the mechanism of DHZCP enhancing anti-tumor immunity, which showed more Th1 cells in the peripheral blood and spleen after DHZCP treatment, while more IFN-γ was secreted to activate CD8+ T cells and Treg cell production was inhibited, thereby suppressing the growth of HCC. Finally, we also analyzed the potential components of DHZCP from the perspective of modern targets using network pharmacology methods and experimental results.


Subject(s)
Animals , Humans , Mice , CD8-Positive T-Lymphocytes , Carcinoma, Hepatocellular/drug therapy , Drugs, Chinese Herbal , Liver Neoplasms/drug therapy , T-Lymphocytes, Regulatory , Tumor Microenvironment
13.
Journal of Experimental Hematology ; (6): 237-243, 2022.
Article in Chinese | WPRIM | ID: wpr-928700

ABSTRACT

OBJECTIVE@#To investigate the role of relationship between the expression of miRNA181a-5p and imbalance of Treg/Th17 in the pathogenesis of primary immune thrombocytopenia(ITP), which contributes to clarify the mechanism of T cell immune imbalance in ITP patients.@*METHODS@#Peripheral blood was collected from 37 ITP patients, concluding 21 untreated patients and 16 effectively treated patients, and 19 healthy controls; Peripheral blood mononuclear cells (PBMC) were isolated and the expression of miRNA181a-5p and Notch1 was analyzed by RT-PCR. The proportion of Th17 subsets and Treg cells in the peripheral circulation was detected by flow cytometer (FCM). Clinical data of ITP group was collected, including age, platelet count and disease course.@*RESULTS@#The expression of miR-181a-5p was significantly decreased in ITP group than that of healthy control group (P<0.01). After effective treatment, the expression of miR-181a-5p was significantly higher than that of ITP group (P<0.05), but still significantly lower than that of healthy control group (P<0.01); The expression of Notch1 was significantly increased in ITP group and effectively treated group than that of healthy control group (P<0.01). There was no significant difference in proportion of Treg cells in ITP group, effectively treated group and healthy control group (P>0.05). The proportion of Th17 subsets in ITP group was significantly increased than that of healthy control group (P<0.05), while the ratio of Treg/Th17 was significantly decreased (P<0.05). There was a positive correlation between the expression of miR-181a-5p and ratio of Treg/Th17 in ITP group (r=0.555).@*CONCLUSION@#The expression of miR-181a-5p is significantly decreased in ITP patients, which is closely related to the imbalance of Treg/Th17 cells. After effective treatment, the expression of miR-181a-5p can be significantly corrected, but still failed to reach the level of healthy people. While the expression of Notch1 is significantly increased in ITP patients, and could not reach the level of healthy people after effective treatment.


Subject(s)
Humans , Leukocytes, Mononuclear , Platelet Count , Purpura, Thrombocytopenic, Idiopathic , T-Lymphocytes, Regulatory , Th17 Cells
14.
Journal of Experimental Hematology ; (6): 36-42, 2022.
Article in Chinese | WPRIM | ID: wpr-928667

ABSTRACT

OBJECTIVE@#To investigate regulatory T cells (Tregs) relative content in peripheral blood and bone marrow of patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) treated with or without decitabine (DAC), analyze the immunomodulatory of Tregs in pathogenesis and remission of MDS and AML, as well as effect of DAC on Tregs.@*METHODS@#From October 2018 to February 2019, 15 patients with MDS and 49 patients with AML (newly diagnosed, treated with DAC or other chemotherapy regimens) were enrolled in this study, and 14 cases with iron deficiency or megaloblastic anemia while without malignant tumor and autoimmune disease as controls. The Tregs relative contents in bone marrow and peripheral blood were analyzed by flow cytometry, meanwhile clinical data of the objects were collected.@*RESULTS@#In peripheral blood and bone marrow of the patients with MDS and AML, the Tregs relative contents at newly diagnosed were higher than those of the control group (P=0.05, P=0.043). The Tregs relative content of AML patients in DAC regimen treatment group was significantly lower than that in the newly diagnosed group and non-DAC chemotherapy group (P<0.05). In DAC regimen treatment group, the Tregs relative contents was significantly lower in remission group than in non-remission group (P<0.05). There was no difference between DAC regimen treatment group and control group in Tregs relative content.@*CONCLUSION@#DAC may increase the body's anti-tumor immunity by consuming Tregs content, enhance the body's immune function to identify and kill tumor cells, thereby promote the patients' reliefs.


Subject(s)
Humans , Antineoplastic Combined Chemotherapy Protocols , Bone Marrow , Decitabine/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Myelodysplastic Syndromes/drug therapy , T-Lymphocytes, Regulatory , Treatment Outcome
15.
Journal of Integrative Medicine ; (12): 453-462, 2022.
Article in English | WPRIM | ID: wpr-939897

ABSTRACT

OBJECTIVE@#Rheumatoid arthritis (RA) progression is associated with the balance of T-regulatory (Treg) and T-helper 17 (Th17) cells, while the role of microRNAs (miRs) in regulating Treg/Th17 cell balance has not been clarified. This study aimed to assess whether moxibustion could regulate Treg/Th17 cell balance by modulating the miR-221/suppressor of cytokine signaling 3 (SOCS3) axis in the RA mouse model.@*METHODS@#A mouse model of collagen-induced arthritis (CIA) was established in male DBA/1J mice. Twenty-two days after CIA induction, the mice received daily treatment with moxibustion for 12 times. Pathological scores were assessed according to the levels of synovial hyperplasia. The expression levels of cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-17 and IL-10 were analyzed in serum by enzyme-linked immunosorbent assay. The cluster of differentiation 4 (CD4+) splenocytes was analyzed by fluorescence-activated cell sorting. The expression levels of RA-related miRs and target genes were subsequently detected, and the target of miR-221 was confirmed by the dual-luciferase reporter assay.@*RESULTS@#It was revealed that moxibustion treatment decreased the pathological scores and downregulated the expression levels of IL-1β, IL-6, TNF-α, IFN-γ and IL-17, while upregulated the expression level of IL-10. The Treg/Th17 cell balance was regulated by moxibustion treatment. The expression level of miR-221 was suppressed by moxibustion treatment. Furthermore, SOCS3 was found as the direct target of miR-221, which mediated the function of moxibustion by regulating the Treg/Th17 cell balance.@*CONCLUSION@#Moxibustion therapy regulated the Treg/Th17 cell balance by modulating the miR-221/SOCS3 axis in the RA mouse model.


Subject(s)
Animals , Male , Mice , Arthritis, Experimental/therapy , Arthritis, Rheumatoid/therapy , Cytokines , Disease Models, Animal , Interleukin-10 , Interleukin-17 , Interleukin-6 , Mice, Inbred DBA , MicroRNAs/genetics , Moxibustion , T-Lymphocytes, Regulatory , Th17 Cells/pathology , Tumor Necrosis Factor-alpha
16.
Frontiers of Medicine ; (4): 483-495, 2022.
Article in English | WPRIM | ID: wpr-939876

ABSTRACT

The pathological hallmarks of psoriasis involve alterations in T cell genes associated with transcriptional levels, which are determined by chromatin accessibility. However, to what extent these alterations in T cell transcriptional levels recapitulate the epigenetic features of psoriasis remains unknown. Here, we systematically profiled chromatin accessibility on Th1, Th2, Th1-17, Th17, and Treg cells and found that chromatin remodeling contributes significantly to the pathogenesis of the disease. The chromatin remodeling tendency of different subtypes of Th cells were relatively consistent. Next, we profiled chromatin accessibility and transcriptional dynamics on memory Th/Treg cells. In the memory Th cells, 803 increased and 545 decreased chromatin-accessible regions were identified. In the memory Treg cells, 713 increased and 1206 decreased chromatin-accessible regions were identified. A total of 54 and 53 genes were differentially expressed in the peaks associated with the memory Th and Treg cells. FOSL1, SPI1, ATF3, NFKB1, RUNX, ETV4, ERG, FLI1, and ETC1 were identified as regulators in the development of psoriasis. The transcriptional regulatory network showed that NFKB1 and RELA were highly connected and central to the network. NFKB1 regulated the genes of CCL3, CXCL2, and IL1RN. Our results provided candidate transcription factors and a foundational framework of the regulomes of the disease.


Subject(s)
Humans , Chromatin/genetics , Chromatin Assembly and Disassembly , Gene Regulatory Networks , Psoriasis/genetics , T-Lymphocytes, Regulatory
17.
Journal of Experimental Hematology ; (6): 970-974, 2022.
Article in Chinese | WPRIM | ID: wpr-939718

ABSTRACT

Langerhans cell histiocytosis (LCH) is a rare proliferative disease dominated by the proliferation of Langerhans cells, which is inflammatory myeloid neoplasms. Its clinical manifestations are variable, occurring at any age and at any site, and it is rarer in adults than in children. The gold standard for diagnosis is histopathological biopsy. Due to the rarity of adult LCH and the heterogeneity of this disease, treatment of adult LCH should be developed according to the extent of the disease and risk stratification. With the discovery of MAPK, PI3K and c-KIT signaling pathway activation, especially BRAF V600E and MAP2K1 mutations, targeted therapy has become a hot spot for therapeutic research. Meanwhile, the discovery of high expression of M2-polarized macrophages and Foxp3+ regulatory T cells (Treg) in LCH has provided an important basis for the immunotherapy. In this article, we will focus on reviewing the latest research progress in the treatment of adult LCH in recent years, and provide a reference for clinical research on the treatment of adult LCH patients.


Subject(s)
Adult , Child , Humans , Histiocytosis, Langerhans-Cell/therapy , Mutation , Proto-Oncogene Proteins B-raf/metabolism , Signal Transduction , T-Lymphocytes, Regulatory/pathology
18.
Chinese Journal of Otorhinolaryngology Head and Neck Surgery ; (12): 142-152, 2022.
Article in Chinese | WPRIM | ID: wpr-936187

ABSTRACT

Objective: To detect the percentages of CD8+Treg cells in the nasal mucosa and peripheral blood of chronic rhinosinusitis (CRS) and to explore their correlation with eosinophilic infiltration. Methods: Thirty-three chronic rhinosinusitis with polyp (CRSwNP), 26 chronic rhinosinusitis without polyp (CRSsNP) and 27 control patients who were collected with the nose mucosal tissue and peripheral blood in the Third Affiliated Hospital of Sun Yat-sen University from March 2017 to October 2018 were selected, including 59 males and 27 females, aging from 18 to 72 years. Hematoxylin and eosin (HE) staining was used to observe the number of eosinophils in the nasal tissues and to classify the CRS into eosinophilic CRS (ECRS) and non-eosinophilic CRS (Non-ECRS). Flow cytometry was used to detect the percentages of CD4+ and CD8+T cells in lymphocytes of nasal mucosa and peripheral blood. The percentages of CD8+Foxp3+Treg cells, CD8+Foxp3-IL-10+Treg cells, CD8+IFN-γ+T cells (Tc1), CD8+IL-4+T cells (Tc2) and CD8+IL-17A+T cells (Tc17) in lymphocytes of nasal mucosa and peripheral blood were also tested. Besides, the percentages of Foxp3+TGF-β+Treg cells and Foxp3+IL-10+Treg cells in CD8+T cells were determined. All data were represented by M (IQR). GraphPad 7.0 and SPSS 16.0 were used for illustration and statistical analysis. Results: The percentage of CD8+T cells (37.75%(17.35%)) was higher than that of CD4+T cells (4.72%(4.29%)) in nasal mucosa (Z=-5.70, P<0.001), while lower (23.60%(9.33%)) than that of CD4+T cells (44.05% (10.93%)) in peripheral blood (t=9.72, P<0.001). CRSwNP patients possessed the highest Tc2 (1.82% (1.22%)) and Tc17 (1.93% (2.32%)) percentages than CRSsNP (Tc2: 0.84% (0.79%); Tc17: 0.54% (1.04%)) and control (Tc2: 1.09% (0.92%); Tc17: 0.47% (0.51%), both P<0.05) patients. While, CRSwNP patients possessed the lowest CD8+Foxp3+Treg cells percentage (0.10% (0.32%)) than CRSsNP (0.43% (1.45%)) and control (0.48% (0.83%), Z value was -2.24, -2.22, respectively, P value was 0.025, 0.027, respectively). The percentages of Foxp3+TGF-β+Treg cells and Foxp3+IL-10+Treg cells of CD8+T cells in nasal mucosa in CRSwNP were also lower than controls (Z value was 1.46, 0.49, respectively, both P=0.001). Moreover, the percentage of CD8+Foxp3-IL-10+Treg cells of CD8+T cells was decreased in nasal mucosa of CRSwNP patients (0.14% (0.28%)) when compared with that of CRSsNP (0.89% (0.81%), Z=0.61, P=0.03). ECRS patients had the lower percentages of CD8+Foxp3+Treg cells (0.07% (0.44%)) and CD8+Foxp3-IL-10+Treg cells (0.13% (0.21%)) than Non-ECRS patients (CD8+Foxp3+Treg cells: 0.53% (0.75%); CD8+Foxp3-IL-10+Treg cells: 0.29% (0.76%), t value was 2.14, 2.78, respectively, both P<0.05). The percentage of CD8+Foxp3+Treg cells and the ratio of CD8+Foxp3-IL-10+T per CD8+T cells were negatively correlated with the percentage of eosinophils in CRS patients(R2 value was 0.56, 0.78, respectively, both P<0.001). There was no significant difference in the distribution of CD8+Fxop3+Treg cells and CD8+Fxop3-IL-10+Treg cells in peripheral blood among different groups. Conclusion: The percentages of CD8+Treg cells decrease in CRSwNP patients, especially in ECRS patients, which are opposite to that of Tc2 and Tc17, and negatively correlate with the eosinophils percentage. This indicates that the decrease in the ratio of CD8+Treg cell may be associated with the immune-imbalance and eosinophilic infiltration in nasal mucosa of CRS patients.


Subject(s)
Female , Humans , Male , CD8-Positive T-Lymphocytes , Chronic Disease , Nasal Polyps/complications , Rhinitis/complications , Sinusitis/complications , T-Lymphocytes, Regulatory
19.
Journal of Peking University(Health Sciences) ; (6): 272-277, 2022.
Article in Chinese | WPRIM | ID: wpr-936146

ABSTRACT

OBJECTIVE@#To evaluate the effects of hepatitis B virus (HBV) on helper T lymphocytes 17 (Th17), regulatory T lymphocyte (Treg) and Th17/Treg ratio in chronic hepatitis B patients in different alanine aminetransferase (ALT) stages.@*METHODS@#In the study, 336 chronic hepatitis B patients in the first hospital of Lanzhou University were analyzed. The hepatitis B antigen antibody parameters were measured by chemiluminescence immunoassay analyzer, the liver function parameters were measured by automatic biochemical analyzer, the HBV loads were measured by quantitative PCR, Th17, Treg and Th17/Treg ratios were detected by flow cytometry. Among them, 111 cases (ALT < 40 U/L) of ALT were normal hepatitis B, 108 cases of chronic hepatitis B with ALT above normal upper limit and < 2 times higher (40 U/L≤ALT < 80 U/L), and 117 cases of chronic hepatitis B with ALT above 2 times normal upper limit (80 U/L≤ALT). According to the viral load, they were divided into low replication group with HBV DNA < 4.0 lg copies/mL, medium replication group with 4.0 lg copies/mL≤HBV DNA < 6.0 lg copies/mL and high replication group with HBV DNA ≥ 6.0 lg copies / mL. Dunnett T3 variance analysis were used to analyze the effects of HBV on Th17, Treg and Th17/Treg ratio in the chronic hepatitis B patients in different ALT stages. The changes of virological and immunological indexes before and after treatment were observed for 24 weeks of antiviral therapy in the hepatitis B patients with ALT≥double upper limit of normal group.@*RESULTS@#In the ALT normal group, different virus load HBV had minor effects on Th17, Treg and Th17/Treg ratio. In the ALT≥2 times upper limit of normal group, with the virus load increased, Th17 (3.18%±0.79% in low replication group, 3.78%±0.92% in medium replication group and 4.57%±1.15% in high replication group), Treg cells (5.52%±1.58% in low replication group, 5.89%±1.84% in medium replication group and 6.37%±2.35% in high replication group) and their ratio Th17/Treg (0.57±0.25 in low replication group, 0.65±0.29 in medium replication group and 0.73±0.36 in high replication group) were significantly increased (P < 0.05). After entecavir treatment 24 weeks, the patient' s HBV-DNA decreased significantly, Th17 (3.89%±1.02% vs. 2.06%±0.46%), Treg (6.02%±2.03% vs. 5.06%±1.25%), Th17/Treg ratio (0.65±0.28 vs. 0.41±0.14) decreased significantly (P < 0.05).@*CONCLUSION@#Investigation on the effects of HBV on Th17 and Treg cells and their ratios in different ALT states can clarify the effects of HBV on the body from the immunological perspective and can further understand the ALT grouping for antiviral treatment theoretical significance, which is helpful for clinical treatment.


Subject(s)
Humans , Alanine/therapeutic use , Alanine Transaminase/therapeutic use , Antiviral Agents/therapeutic use , DNA, Viral/therapeutic use , Hepatitis B/drug therapy , Hepatitis B virus/genetics , Hepatitis B, Chronic/drug therapy , T-Lymphocytes, Regulatory
20.
China Journal of Chinese Materia Medica ; (24): 1300-1306, 2022.
Article in Chinese | WPRIM | ID: wpr-928056

ABSTRACT

This study aims to investigate the regulatory effect of Sishen Pills(SSP) and its split prescriptions Ershen Pills(EP) and Wuweizi Powder(WP) on T follicular helper(Tfh) cell subset in the dextran sodium sulfate(DSS)-induced colitis mice and the mechanism. A total of 60 male SPF BALB/c mice were used, 10 of which were randomly selected as the normal group. The rest 50 were induced with 3% DSS solution for colitis modeling. After modeling, they were randomized into 5 groups: model group, SSP group, EP group, WP group, and mesalazine group. Body mass, colon mass, colon mass index, colon length, and unit colon mass index in each group were observed. After hematoxylin-eosin(HE) staining, the pathological injury of colon tissue was scored. The expression levels of molecules related to the STAT/SOCS signaling pathway in colon tissues were analyzed by Western blot. Differentiation levels of Tfh cells such as CD4~+CXCR5~+IL-9~+(Tfh9), CD4~+CXCR5~+IL-17~+(Tfh17), and CD4~+CXCR5~+Foxp3~+(Tfr) in peripheral blood of mice were detected by flow cytometry. The results showed each treatment group demonstrated significant increase in body mass and colon length, decrease in colon mass, colon mass index, unit colon mass index, and histopathological score(P<0.05, P<0.01), reduction of the expression of p-STAT3, STAT3, p-STAT6, and STAT6(P<0.05, P<0.01), rise of the expression of SOCS1 and SOCS3(P<0.05, P<0.01), decrease of Tfh9 and Tfh17 cells, and increase of Tfr cells(P<0.05, P<0.01) compared with the model group. These results indicated that SSP and the split EP and WP may alleviate ulcerative colitis by inhibiting the activation of STAT/SOCS signaling pathway and regulating the balance of Tfr/Tfh9/Tfh17 cells.


Subject(s)
Animals , Male , Mice , Colitis/genetics , Colitis, Ulcerative/metabolism , Mice, Inbred BALB C , Prescriptions , T-Lymphocytes, Regulatory
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