Regulation of Immune Balance by Traditional Chinese Medicine in Treatment of Cough Variant Asthma： A Review / 中国实验方剂学杂志

Cough variant asthma （CVA） is a chronic respiratory disease with cough as its main symptom. The occurrence of CVA is closely related to non-specific airway inflammation， and its pathogenesis involves environmental， genetic， immune， and other factors. In recent years， the advantages of traditional Chinese medicine （TCM） in the treatment of CVA have attracted the attention of experts and scholars in China and abroad， especially its prominent role in regulating immune balance， relieving cough symptoms in CVA patients， and reducing recurrence. T Helper cells 1 （Th1）， T helper cells 2 （Th2）， T helper cells 17 （Th17）， and regulatory T cells （Treg） are derived from CD4+ T cells. Immune imbalance of Th1/Th2 and Th17/Treg is a new hotspot in the pathogenesis of CVA and a potential key target in the treatment of CVA by TCM. Th cell subsets are in dynamic balance under physiological conditions， maintaining respiratory immune homeostasis in which pro-inflammatory cytokines and anti-inflammatory cytokines are balanced. Immature helper T cells （Th0） can be differentiated into Th1， Th2， Th17， Treg， and other cell subsets due to cytokine types in the microenvironment in the stage of CVA maturation. The proliferation of Th2 cells leads to eosinophilic airway inflammation. Excessive differentiation of Th17 cells induces neutrophil airway inflammation. Th1/Th2 and Th17/Treg cells are mutually restricted in number and function， and the immune imbalance of Th1/Th2 and Th17/Treg is easy to aggravate the generation of inflammatory response. Restoring immune balance is particularly important for the airway anti-inflammatory therapy of CVA. In this paper， the imbalance of Th1/Th2 and Th17/Treg and the pathogenesis of CVA were systematically expounded. Meanwhile， the latest research on the regulation of immune imbalance by TCM compound， single TCM， and its effective ingredients in the treatment of CVA was reviewed. It provides ideas and references for revealing the scientific connotation of TCM regulating immune balance therapy of CVA， as well as the development of clinical treatment and basic research of CVA.

Effect of acute or subchronic stress on T cell response in peripheral blood: Regulatory role of vitamin D

The immune response, orchestrated by helper (Th1, Th2, and Th17) and regulatory (Treg) T cells, is modulated by stress and Vitamin D (Vit-D). Although the immunomodulatory functions of both are known, their specific roles on Th cells have not been fully clarified, yet. On this background, we aimed to investigate the effect of acute or subchronic stress on the distribution of peripheral T lymphocytes, as well as the immunomodulatory role of Vit-D. Young adult male, Swiss-albino mice (30–40g) were allocated to the control, acute stress (AS), subchronic stress (ChS), control+Vit-D, AS+Vit-D, and ChS+Vit-D groups (n=11/group). The combined cold (2-h at 4°C)-immobilization (2-h in a restrainer) stress protocol was employed as one day in AS groups and five consecutive days in ChS groups. Vit-D (2?g/kg ip) was applied every other day, until the end of the protocol. Serum cortisol, Vit-D and cytokine levels (IL-4, IFN-?, and IL-17A) were measured, and lymphocytes from blood samples were subtyped by flow-cytometry. Stress exposure caused differential Th and Treg responses, acute stress shifting the response to Th1, and subchronic stress shifting the response to Th2. Th17 and Treg cells were lower in subchronic stress exposed mice. These changes became comparable to control values in Vit-D treated groups. The T cell response, crucial for immune system function, differs on the basis of stress exposure as such the Vit-D treatment. The tolerogenic profile created by Vit-D should be considered for management of stress-related diseases. Our results may help to provide a better understanding of disease pathogenesis.

Effect of Fugan Huaxian Decoction （扶肝化纤汤） on Th17/Treg Balance and Related Transcription Factors in Hepatic Fibrosis with Healthy Qi Deficiency and Toxin Accumulation Pattern Model Rats / 中医杂志

ObjectiveTo investigate the possible mechanism of Fugan Huaxian Decoction （扶肝化纤汤， FHD） against hepatic fibrosis （HF） from the perspective of immunity. MethodsForty-eight SD rats were randomly divided into blank group， model group， colchicine group， FHD high-， medium- and low-dose group， with eight rats in each group. Except for the blank group， the disease-syndrome combined model of HF with healthy qi deficiency and toxin accumulation pattern was established during six weeks in the other five groups. After successful modeling， the high-， medium- and low-dose FHD groups were respectively given 37.5， 18.75 and 9.38 g/（kg·d） of FHD granules by gavage， while the colchicine group received 2 mg/ （kg·d） of colchicine tablets by gavage， and the blank group and the model group were given 10 ml/（kg·d） of purified water， all for 3 weeks. The general condition of the rats was recorded. After the treatment， the histopathological morphology of the liver was observed by HE staining， and the levels of interleukin 10 （IL-10） and interleukin 17 （IL-17） in serum were determined by enzyme-linked immunosorbent assay （ELISA）. The expression of helper T cells 17 （Th17） and regulatory T cells （Treg） in peripheral blood were detected by flow cytometry， and the Th17/Treg value was calculated. The mRNA expression of retinoic acid-related nuclear orphan receptor γ （RORγt） and fork-head/wing-like helix transcription factor （FoxP3） in liver tissue were detected by qRT-PCR. ResultsCompared to the general condition of rats in the blank group， those in the model group were listless， less active， stretched and pushed， arched and prone， having no resistance to gavage， significantly reduced food intake， loose stools， dirty anus， slow weight gain， dry and dull hair， purple and darkening skin of the limbs with ecchymoses， purple and black spots with varying degrees of the skin of the tail； hepatic fibrosis and hyperplasia of rats in model group were more obvious； serum IL-17， peripheral blood Th17 expression and Th17/Treg value， RORγt mRNA expression in the liver tissue significantly increased in the model group， while expression of IL-10， Treg and FoxP3 mRNA significantly decreased （P＜0.05 or P＜0.01）. Compared to those in the model group， the general condition of the rats and the liver fibrosis of HE stained liver tissue were improved in all the medication groups； the expression of IL-17 and Th17， Th17/Treg， and RORγt mRNA expression significantly decreased， while expression of IL-10， Treg， and FoxP3 mRNA increased in the high- and medium-dose FHD groups and the colchicine group； the expression of IL-17， Th17， and RORγt mRNA decreased， while the expression of IL-10 and FoxP3 mRNA increased in the low-dose FHD group （P＜0.05 or P＜0.01）. And more improvements were found in the FHD high-dose group than FHD medium- and low-dose groups and colchicine group （P＜0.05 or P＜0.01）. ConclusionFHD can may regulate immune balance and act against fibrosis by regulating the expression of specific transcription factors FoxP3 and RORγt， affecting the differentiation of Th17 and Treg cells and Th17/Treg balance， and regulating the secretion of IL-10 and IL-17.

JAK inhibition ameliorated experimental autoimmune encephalomyelitis by blocking GM-CSF-driven inflammatory signature of monocytes

Monocytes are key effectors in autoimmunity-related diseases in the central nervous system (CNS) due to the critical roles of these cells in the production of proinflammatory cytokines, differentiation of T-helper (Th) cells, and antigen presentation. The JAK-STAT signaling is crucial for initiating monocytes induced immune responses by relaying cytokines signaling. However, the role of this pathway in modulating the communication between monocytes and Th cells in the pathogenesis of multiple sclerosis (MS) is unclear. Here, we show that the JAK1/2/3 and STAT1/3/5/6 subtypes involved in the demyelination mediated by the differentiation of pathological Th1 and Th17 and the CNS-infiltrating inflammatory monocytes in experimental autoimmune encephalomyelitis (EAE), a model for MS. JAK inhibition prevented the CNS-infiltrating CCR2-dependent Ly6Chi monocytes and monocyte-derived dendritic cells in EAE mice. In parallel, the proportion of GM-CSF+CD4+ T cells and GM-CSF secretion were decreased in pathological Th17 cells by JAK inhibition, which in turns converted CNS-invading monocytes into antigen-presenting cells to mediate tissue damage. Together, our data highlight the therapeutic potential of JAK inhibition in treating EAE by blocking the GM-CSF-driven inflammatory signature of monocytes.

Linkage of blood cell division cycle 42 with T helper cells, and their correlation with anxiety, depression, and cognitive impairment in stroke patients

Cell division cycle 42 (CDC42) regulates T helper (Th) cell differentiation and is related to psychological disorders. This study aimed to assess the correlation between blood CDC42 and Th cells, and their association with mental issues in stroke patients. Peripheral blood samples were obtained from 264 stroke patients and 50 controls. Then, serum CDC42 was measured by enzyme-linked immunosorbent assay, and Th1, Th2, and Th17 cells were detected by flow cytometry. Hospital Anxiety and Depression Scale (HADS) and Mini Mental State Examination (MMSE) were applied to patients. CDC42 was decreased (P<0.001), Th1 (P=0.013) and Th17 (P<0.001) cells were elevated, while Th2 cells (P=0.108) showed no difference in stroke patients compared to controls. In addition, CDC42 was negatively associated to Th1 (P=0.013) and Th17 (P<0.001) cells in stroke patients but were not associated with Th2 cells (P=0.223). Interestingly, CDC42 was negatively associated with HADS-anxiety (P<0.001) and HADS-depression scores (P=0.034) and positively associated with MMSE score (P<0.001) in stroke patients. Lower CDC42 was associated to lower occurrence of anxiety (P=0.002), depression (P=0.001), and cognitive impairment (P=0.036) in stroke patients. Furthermore, increased Th17 cells were positively correlated with HADS-anxiety and HADS-depression scores and inversely correlated with MMSE score, which were also associated with higher occurrence of anxiety, depression, and cognitive impairment in stroke patients (all P<0.05). Blood CDC42 and Th17 cells were correlated, and both of them were linked to the risk of anxiety, depression, and cognitive impairment. However, the findings need further large-scale validation, and the implicated mechanism needs more investigation.

The sensitization of thymic stromal lymphopoietin to type 2 lymphocytes in the lung / 国际儿科学杂志

Thymic stromal lymphopoietin(TSLP)can enhance the secretion of type 2 cytokines by type 2 T helper(Th2)cells and type 2 innate iymphocytes(ILC2s)in the lung through direct and indirect action.In terms of indirect effects, TSLP can promote the proliferation and expansion of naive CD4 + T cells by using dendritic cells, and promote the recruitment of Th2 cells to the initial inflammatory site.It can also use stromal mononuclear/macrophages cells to start the acute primary Th2-dependent immune response.In the aspect of direct effect, TSLP can activate ILC2s before the adaptive immune response is initiated, and also can use immature T cells, effector Th2 cells and memory Th2 cells to participate in the adaptive immune response.Therefore, TSLP plays an important role in allergic immune response of lung.

Therapeutic Effect of Mesenchymal Stem Cells Overexpressing Interleukin-10 on Inflammatory Bowel Disease / 中国生物化学与分子生物学报

Inflammatory bowel disease (IBD) is an, intractable inflammatory autoimmune disease characterized by T-cell infiltration to the colon. Mesenchymal stem cells (MSCs), owing to their immunosuppressive capabilities, have the potential to rescue IBD. But the therapeutic effectiveness of MSCs is sometime thwarted by their variable immunomodulatory ability in vivo. In the present study, we produced engineered MSCs that secrete interleukin10 (IL-10) and evaluated their therapeutic potential in IBD mouse model. The MSCs maintained the phenotype and cell proliferation rate after overexpression of IL-10 by lentivirus (LV) infection. Immune cells and MSCs in vitro co-culture systems exhibited that relative to unmodified MSCs, immune cells co-cultured with IL-10-overexpressing MSCs had significantly lower numbers of T helper 1 cells (Th1) and T helper 17 cells (Th17) (P0.05). Overall, LV induced MSCs overexpressing IL-10 might be a promising alternative therapeutic option for the treatment of IBD.

Diagnostic Value of Bcl-2, miR-451 and Th17 Cells in Esophageal Cancer and Their Relation with Recurrence / 肿瘤防治研究

Objective To investigate the diagnostic value of Bcl-2, miR-451 and Th17 cells in esophageal cancer and their relation with recurrence. Methods We selected 101 patients with esophageal cancer as the experimental group and 95 healthy patients as the control group. The correlation between the clinicopathological characteristics and the level of each peripheral blood index was analyzed. The ROC curve was used to analyze the diagnostic value of each peripheral blood index. Multiple linear regression analysis was used to analyze the relation between each index and tumor recurrence. Results Peripheral blood Bcl-2, miR-451 and Th17 cells in the experimental group were higher than those in the control group (all P < 0.05); differentiation degree, clinical stage, tumor diameter and lymph node metastasis were positively correlated with the levels of Bcl-2, miR-451, and Th17 cells (all P < 0.05). Bcl-2, miR-451 and Th17 cells in relapsed patients were higher than those in non-relapsed patients (all P < 0.05); after controlling other factors such as differentiation degree, clinical stage, tumor size and lymph node metastasis, the levels of Bcl-2, miR-451 and Th17 cells were significantly correlated with recurrence (all P < 0.05). Conclusion Bcl-2, miR-451 and Th17 cells in peripheral blood of esophageal cancer patients are abnormally expressed and their expression are closely related to differentiation degree, clinical stage and recurrence. The combined detection could provide an objective basis for clinical diagnosis and prognosis assessment.

Research progress on the role of T helper cells 17 and interleukin 17 in oral mucosal diseases / 口腔疾病防治

@#T helper 17 (Th17) cells are a new type of CD4+ T helper cell. They participate in the immune and inflammatory response by secreting specific interleukin-17 (IL-17). In oral mucosal diseases, oral lichen planus (OLP), recurrent aphthous ulcer (RAU) and Behcet′s disease (BD) are associated with Th17 cells and IL-17. There were 17 kinds of proteins in the saliva of patients with OLP that could upregulate the expression of Th17 cells and induce the secretion of IL-17. IL-17 can stimulate epithelial cells, endothelial cells and fibroblasts to produce a variety of cytokines, such as IL-6, IL-8, granulocyte macrophage colony-stimulating factor and cell adhesion molecule-1, leading to the production and aggravation of inflammation. Th17/Tc17 cell-targeted therapy can significantly improve the clinical symptoms of OLP patients′ mucosa and skin. IL-17 can stimulate oral keratinocytes through the IL-17RA or IL-17RE receptor and produce proinflammatory effects in RAU. Th17 cells in the peripheral blood of BD patients are significantly increased, while Treg cells are significantly decreased.

Progress of immune functions of T helper cells 17 and regulatory T cells and their immunomodulatory effect on non-small cell lung cancer / 肿瘤研究与临床

Under the regulation of various cytokines and different concentrations of cytokines, primary CD4+ T cells can differentiate into different Th subgroups. T helper cells 17 (Th17) and regulatory T cells (Treg cells) are research hotspots in recent years. They play diverse immunomodulatory roles by secreting various target cytokines. Th17 and Treg cells are different from each other but connect with each other, their regulatory mechanism is complex, and they play important roles in non-small cell lung cancer (NSCLC). This paper reviews the progress of the differentiation, the development and the immunological function of Th17 and Treg cells and their immunomodulatory effect on the NSCLC.

Effects of compound sophora flavescens injection on T helper cells 17, regulatory T cells and the related cytokines in lung cancer patients with cirrhosis / 肿瘤研究与临床

Objective@#To investigate the effect of compound sophora flavescens injection on T helper cells 17 (Th17), regulatory T-cells (Treg cells) and the related cytokines in lung cancer patients with cirrhosis.@*Methods@#A total of 63 patients with early non-small cell lung cancer and cirrhosis in Shouguang People's Hospital of Shandong Province from January 2016 to January 2018 were selected. All patients were scheduled to undergo surgical treatment. The patients were randomly divided into observation group (33 cases) and control group (30 cases) according to the random number table method. The patients in the control group were treated with liver protection, and the patients in the observation group were given compound sophora flavescens on the basis of the control group. After 3 months of treatment, the changes of liver fibrosis index, the levels of Th17 and Treg cells in peripheral blood and the changes of interleukin (IL)-10, IL-17, IL-6, and transforming growth factor (TGF)-β in serum were compared between the two groups.@*Results@#After treatment, the alanine aminotransferase (ALT) of 15 cases (45.45%) in the observation group were normalized and 6 cases (20.00%) in the control group were normalized. There was a significant difference in ALT normalization rate between the two groups (P < 0.05). The levels of serum laminin (LN) and hyaluronic acid (HA) in the two groups after treatment were lower than those before treatment (all P < 0.05), and the serum LN [(156.74±30.52) ng/ml] and HA [(179.56±25.32) ng/ml] in the observation group after treatment was lower than those in the control group [(210.58±39.42) ng/ml and (203.75±28.79) ng/ml] (t values were 18.236 and 12.184, both P < 0.01). There was no significant difference in the level changes of type Ⅲ procollagen and type Ⅳ collagen between the two groups before and after treatment (all P > 0.05). After treatment, the levels of Th17 and Th17/Treg increased and the level of Treg cells decreased (all P < 0.05). After treatment, the levels of Th17 [(1.32±0.18)%] and Th17/Treg (0.23±0.04) in the observation group were higher than those in the control group [(1.21±0.17)% and 0.20±0.03] (t values were 3.201 and 1.087, both P < 0.01), while the level of Treg cells in the observation group was lower than that in the control group (P < 0.05). After treatment, the serum levels of IL-10, IL-17, IL-6, and TGF-β in the two groups were lower than those before treatment (all P < 0.05), and their levels in the observation group were lower than those in the control group (all P < 0.05).@*Conclusion@#Compound sophora flavescens injection can improve the liver function and fibrosis index of patients with lung cancer and cirrhosis, and it can regulate the levels of Th17, Treg cells and their related factors, which can be used as a clinical adjuvant.

Primary epiglottic follicular variant of peripheral T-cell lymphoma

The follicular variant of peripheral T-cell lymphoma, not otherwise specified, is very rare. Primary epiglottic follicular variant of peripheral T-cell lymphoma is extremely rare in clinical practice. Here, we report the first case of a follicular variant of peripheral T-cell lymphoma not otherwise specified in a 44-year-old Chinese man, who presented with a tumor in the middle of the epiglottis tongue surface. Microscopically, the tumor had a vague nodular growth pattern and the morphology of the nodules was different from each other at low power. Atypical lymphoid cells were medium to large in size and had round nuclei, with an irregular nuclear membrane, distinct nucleoli, and rapid mitotic activity. Plasma cells were found surrounding the nodules. The tumor cells were positive for follicular helper T-cell markers (CD10, PD-1, CXCL13, and BCL-6). The EBER was negative by in situ hybridization. Polymerase chain reaction-based analysis showed monoclonal rearrangements of TCR?, TCR?, and polyclonal rearrangements of IgH, IgK, and IgL. The clinical and imaging features and the prognostic factors of FV PTCL-NOS remain poorly understood. Thus, investigation of more cases and longer follow-up is necessary to understand the disease and to identify the best treatment to improve prognosis.

Guizhi decoction suppresses mouse allergic contact dermatitis by inhibiting differentiation of lymphocytes to Th2 cells / 中国药理学通报

Aim To reveal the effects of Guizhi decoction (G Z D) on allergic contact dermatitis by establishing the mouse allergic contact dermatitis model induced by fluoresciniso thiocyate (FITC) and culturing splenic lymphocytes. Methods BALB/c mice were sensitized by smearing the 1.5% FITC on the shaved abdomens on day 1 and day 2 and elicited on the right ear with 0. 6% FITC solution on day 6. GZD was administered from day 1 to day 7. Ear thickness was measured 24 h after elicitation. HE staining was performed for pathohistological examination. Interleukin-4 (I L - 4), IL-5, IL-9, interferon γ(IFN-γ) in ear tissue homogenates and IgE in serum were detected. The splenic lymphocytes were stimulated with ConA. Results The ear swelling was significantly suppressed by administering GZD. GZD reduced the infiltration of inflammatory cells and edema in the ear, and the levels of I L 4, IL-9, IFN7 and IgE. GZD could also reduce the expression of I L 4, IL-10, IFNγ and GATA3. Conclusions GZD could suppress allergic contact dermatitis elicited by FITC, which may result from inhibiting the differentiation of lymphocytes to Th2 cells.

Role of intestinal flora disturbance in development of POCD in aged mice: the relationship with Treg and Th1/Th2 cells in small intestine / 中华麻醉学杂志

Objective To evaluate the role of intestinal flora disturbance in development of postoperative cognitive dysfunction (POCD) in aged mice and the relationship with regulatory T cells (Treg) and T helper cells 1/T helper cells 2 (Th1/Th2) in the small intestine.Methods Thirty-six SPF healthy male C57BL/6J mice,weighing 45-50 g,aged 18 months,were divided into 3 groups (n=12 each) using a random number table method:control group (group C),POCD group and POCD plus VSL#3 group (group PV).POCD was induced by abdominal exploration.VSL#3 probiotics was given by intragastric gavage (300 μl per time,once a day) every 24 h for 7 consecutive days starting from the end of surgery in group PV.Morris water maze test was used to assess the cognitive function at day 7 after operation.Orbital venous blood samples were collected after the end of Morris water maze test,and animals were then sacrificed and small intestine and hippocampi were removed for measurement of the percentage of CD4+ CD25+ Foxp3+Treg,TCD4+IFN-γ+Th1 and CD4+IL-4+Th2 in the lamina propria of small intestine and plasma and expression of IL-4 and IFN-γmRNA in the lamina propria of small intestine,plasma and hippocampal tissues,and IL-4 mRNA/IFN-γmRNA ratio was calculated.Results Compared with group C,the percentage of CD4+CD25+Foxp3+Treg and CD4+IL-4+ Th2 in the lamina propria of small intestine and plasma was significantly decreased,the percentage of CD4+ IFN-γ+Th1 in the lamina propria of small intestine and plasma was increased,the expression of IL-4 mRNA in the lamina propria of small intestine,plasma and hippocampal tissues was down-regulated,the expression of IFN-γ mRNA in the lamina propria of small intestine,plasma and hippocampal tissues was up-regulated,IL-4 mRNA/IFN-γ mRNA ratio was decreased,the escape latency and swimming distance were prolonged,and the time spent in the target quadrant was shortened in group POCD (P＜0.05).Compared with group POCD,the percentage of CD4+ CD25+ Foxp3+ Treg and CD4+IL-4+ Th2 in the lamina propria of small intestine and plasma was significantly increased,the percentage of CD4+IFN-γ+Th1 in the lamina propria of small intestine and plasma was decreased,the expression of IL-4 mRNA in the lamina propria of small intestine,plasma and hippocampal tissues was upregulated,the expression of IFN-γmRNA in the lamina propria of small intestine,plasma and hippocampal tissues was down-regulated,IL-4 mRNA/IFN-γmRNA ratio was increased,the escape latency and swimming distance were shortened,and the time spent in the target quadrant was prolonged in group PV (P＜ 0.05).Conclusion Intestinal flora disturbance can promote the development of POCD in aged mice,which is related to the decreased percentage of Treg and Th1/Th2 imbalance in the small intestine.

Increased Macroautophagy in Interferon-Gamma-Producing T Cells from Patients with Newly Diagnosed Systemic Lupus Erythematosus / 中华医学杂志(英文版)

<p><b>Background</b>Imbalance of interferon-gamma (IFN-γ), interleukin (IL)-4, and IL-17 producing by T cells is confirmed to contribute to the pathogenesis of systemic lupus erythematosus (SLE). Autophagy is now emerging as a core player in the development and the function of the immune system. Therefore, we investigated the autophagic behavior in IFN-γ-, IL-4-, and IL-17-producing T cells from patients with SLE.</p><p><b>Methods</b>Thirty patients with SLE and 25 healthy controls matched for gender and age were recruited between September 2016 and May 2017. The autophagic levels in IFN-γ T cells, IL-4 T cells, and IL-17 T cells from patients with newly diagnosed SLE and healthy controls were measured using flow cytometry. The plasma levels of IFN-γ were determined by enzyme-linked immunosorbent assay in SLE patients and healthy controls. Unpaired t-tests and the nonparametric Mann-Whitney U-test were used to compare data from patients with SLE and controls. Spearman's rank correlation coefficient was applied for calculation of the correlation between parallel variables in single samples.</p><p><b>Results</b>Our results showed increased percentage of autophagy in IFN-γ T cells from patients with SLE and healthy controls ([8.07 ± 2.72]% vs. [3.76 ± 1.67]%, t = 5.184, P < 0.001), but not in IL-4 T cells or IL-17 T cells (P > 0.05) as compared to healthy donors. Moreover, the plasma levels of IFN-γ in SLE patients were significantly higher than those in healthy controls ([68.9 ± 29.1] pg/ml vs. [24.7 ± 17.6] pg/ml, t = 5.430, P < 0.001). Moreover, in SLE patients, the percentage of autophagy in IFN-γ T cells was positively correlated with the plasma levels of IFN-γ (r = 0.344, P = 0.046), as well as the disease activity of patients with SLE (r = 0.379, P = 0.039).</p><p><b>Conclusion</b>The results indicate that autophagy in IFN-γ T cells from SLE patients is activated, which might contribute to the persistence of T cells producing IFN-γ, such as Th1 cells, and consequently result in the high plasma levels of IFN-γ, and then enhance the disease activity of SLE.</p>

New method of non-alcoholic fatty liver disease mouse models and mechanism about immune cells / 中国药理学通报

Aim To establish non-alcoholic fatty liver disease mouse model and study different kinds of lymphocytes in C57BL/6J mouse model. Methods SPF male C57BL/6J mice were randomly divided into control group ( normal diet ) and model group( normal diet with high fat diet by gavage) . Models of non-alcoholic fatty liver disease were established. At 12th and 16th weeks, body weight, liver index, serum TC, TG, HDL, LDL, ALT, AST were measured. Pathological examination of fat deposition in liver was performed. Flow cytometry was used to assay the percentage of natural killer cells, T helper cells, natu-ral killer T cells and IL4 +NKT cells in mouse liver. Results Liver index, serum TC, LDL, ALT, AST were significantly higher in model group(P<0.05) after 16 weeks. Pathological sections showed that liver fat deposition in model group was quite severe and large lipid droplets spread through the mouse liver. The percentage of natural killer T cells increased significantly( P<0.05 ) and the percentage of IL4 +NKT cells increased even more obviously(P<0.01). Conclusions C57BL/6J mice fed with normal diet and high fat diet by gavage can form a good non-alcoholic fatty liver disease mouse model. In this model, the number and activity of natural killer T cells are significantly changed, and natural killer T cells may be the new target of the mechanism and drug treatment of nonalcoholic fatty liver dis-ease.

Effect of rhIL?11 on Th1/Th2 and T?bet/GATA?3 imbalance in idiopathic thrombocytopenic purpura / 中国综合临床

Objective To investigate the effect of recombinant human interleukin 11(rhlL-11)in the treatment of idiopathic thrombocytopenic purpura(ITP)on the levels of Th1,Th2 and the expression of their transcription factors T-bet mRNA,GATA-3 mRNA.Methods Fifty-six cases adult ITP patients hospitalized in the department of hematology of the Second People's Hospital of Datong from May 2015 to December 2016 were collected,including 21 males and 35 females,aged 29~73 years; 10 healthy people in the same period were enrolled as control group,4 males and 6 females,aged 20~52 years.Th1 and Th2 cell ratio and Th1/Th2 ratio of ITP patients were detected by flow cytometry before and after treatment.The expression levels of transcription factor T-bet and GATA-3 were measured using real-time fluorescence quantitative reverse transcription polymerase chain reaction(RT-PCR)before and after treatment.Results The effective rate of rhlL-11 in ITP treatment was 76.8%(43/56).For the effective patients,the median PLT after treatment increased(25.0(15. 0,36.0)×109/L vs.68.0(49.0,108.0)×109/L,Z=-5.712,P<0.001); Th1 cells decreased,compared with that before the treatment(14.8 %(12.6%,17.6%)vs.10.6 %(9.8%,12.6%),Z=-4.825,P<0.001);Th2 cell increased,compared with that before the treatment(0.4%(0.3%,0.5%)vs.1.2%(0.9%,1.4%), Z=-5.720,P<0.001); Th1/Th2 decreased,compared with that before the treatment(40(30,49)vs.10.6(7.8,12.0),Z=-5.711,P<0.001];the expression level of T-bet mRNA decreased(0.36(0.18,0.51)vs 0.09(0.05,0.13),Z=-2.668,P=0.008);the expression level of GATA-3 mRNA increased,compared with that before treatment(0.04(0.03,0.05)vs.0.12(0.09,0.15),Z=-2.366,P=0.018).For ineffective patients,the median PLT before treatment was(11.0(8.0,15.5)×109/L),and the median PLT after treatment was(15.0(10.0,19.5)×109/L)(Z=-3.027,P=0.002); there was no significant difference in Th1,Th2, ratio of Th1/Th2 and T-bet and GATA-3 mRNA expression level before and after treatment in patients with ITP (P>0.05).Conclusion rhIL-11 can effectively correct the imbalance in Th1 and Th2 cells and the imbalance of T-bet and GATA-3 in ITP patients,but it has no obvious therapeutic effect on a small number of patients

Plasmacytoid dendritic cells and CD4+ T helper cells function in acute and chronic hepatitis B patients / 中华实验和临床病毒学杂志

Objective@#To investigate the differences in function of plasmacytoid dendritic cells (pDC) and CD4+ T helper cells (CD4+ Th cells) between acute hepatitis B (AHB) and chronic hepatitis B (CHB).@*Methods@#In this study, patients with AHB and those with CHB in immune active (IA) phase were enrolled. The frequencies of pDC, CD86+ pDC, CD4+ T cells and their subsets, surface functional molecules were detected respectively among patients with chronic HBV infection in IA phase, patients with AHB, those recovered from AHB. Meanwhile, their correlations with ALT, HBV DNA and HBV markers were analyzed.@*Results@#The ALT level in AHB was significantly higher than that in IA, and inflammation was more obvious in AHB. Between IA and AHB, CD86+ pDC frequency and the mean fluorescence intensity of functional molecule CD86 (CD86MFI) were higher in IA than those in AHB, but the frequency of CD4+ T cells in AHB was higher than that in IA. For patients who got over AHB, the frequency of CD86+ pDC increased; Th1 were on the rise, while the frequencies of CD4+ T and Th2 decreased after the recovery of AHB, and Th2 / Th1 ratio decreased..In AHB, HBVDNA loads were positively correlated with ALT levels and Th2 frequencies.@*Conclusions@#In CHB immune active phase, CD86+ pDC with stimulating function played an important role, but the cellular immune response of CD4+ T cells decreased. In AHB inflammatory stage, CD4+ T cells played a strong cellular immune response, which result ed in viral clearance. Th2 cells regulation of CD4+ T cells played a dominant role, which was involved in the inflammatory response, and the cytotoxic role of Th1 cells during the recovery period was dominant, playing a strong cellular immune response, then the virus were completely eliminated.

Influence of propofol intravenous anesthesia on T helper cells of patients with primary liver cancer in perioperative period / 局解手术学杂志

Objective To study the effect of propofol intravenous anesthesia on T helper cells of patients with primary liver cancer during perioperative period.Methods A total of 86 patients with primary liver cancer in our hospital from November 2014 to October 2015 were selected,who were divided into observation group and control group according to the method of random numbers,43 cases in each group.The observation group were taken propofol intravenous anesthesia,and the control group were treated with sevoflurane inhalation anesthesia.The Th1 cells percentage,Th2 cells percentage and the ratio changes of the Th1/Th2 cells of two groups before anesthesia and postoperative 1 day were compared.The plasma cortisol levels of two groups before anesthesia,after anesthesia,intraoperative and 1 day after operation were observed.Results The percentage of Th2 cells in observation group and control group 1 day after surgery had no significant difference (P ＞ 0.05).The percentage of Th1 cells and Th1/Th2 cells ratio of the observation group were higher than those of the control group [(16.32 ± 1.76) ％ vs.(14.16 ± 1.03),(8.48 ± 0.92) vs.(7.11 ± 0.72)],the differences were significant (P ＜ 0.05).The plasma cortisol levels of observation group during operation and 1 day after operation were lower than those of the control group[(12.34 ± 1.02) μg/dL vs.(16.13 ± 1.26) μg/dL,(12.01 ± 0.94) μg/dL vs.(15.25 ± 1.08) μg/dL],the differences were significant(P ＜ 0.05).Conclusion The propofol intravenous anesthesia can encourage more Th to differentiate into Th1 cells,which plays a protective role in the patient's immune function.

The Immunomodulatory Effects of All-trans Retinoic Acid on AChR-specific Lymphocytes / 现代生物医学进展

Objective:To observe the effects of All-trans retinoic acid (ATRA) on the immune functions of AChR-specific lymphcytes via in vitro assays,and investigate the possibility of ATRA in the clinical treatment of myasthenia gravis (MG).Methods:CFA control group and EAMG experimental rats were established to obtain single lymphocytes suspension and cells were followed by AChR97-116 peptide with or without ATRA stimulation for 72 h,and then viable cell population,cell apoptosis,cell cycle and the distribution of Th cells were determined by flow cytometry.CCK-8 assay was selected to evaluate the effects of ATRA on proliferatory ability of lymphocytes.ELISA was used to detect the antibody secretion of B cells affected by ATRA.Results:Compared with CFA group,lymphocytes obtained from EAMG rats had higher ratios of living cells,and this ratio was obviously decreased after ATRA treatment,P＜0.001.Different concentrations of ATRA promoted the apoptosis of AChR-specific cells (P＜0.001),and the promoted effects were ATRA dose-dependent,however,cell cycles were not changed.ATRA markedly inhibited the proliferation of cells from both CFA and EAMG groups,moreover,AChR-specific cells were more sensitive to ATRA treatment (P＜0.01) than that of cells from CFA rats (P＜0.05).The ratio of AChR-specific CD4+T cells was reduced by ATRA (P＜0.01),and ATRA incubation significantly promoted the percentages of Th2,(PCD4+-4IL-4+＜0.001),Treg (PCD4+-Foxp3+＜0.001) cell types,but markedly inhibited the percentages ofThl7 (PCD4+-IL-17+＜0.05),Thl (PCD4+-IFN-γ+＜0.001) cells.ELISA data showed us that ATRA obviously down regulated the antibody secretion of AChR-specific B cells,P＜0.01.Conclusions:ATRA not only inhibited the functions of AChR-specific T cells,but also suppressed the roles of AChR-specific B cells,predicating a therapeutic effect of ATRA on myasthenia gravis therapy.