Efficient Numerical Scheme for the Solution of HIV Infection CD4^(+)T-Cells Using Haar Wavelet Technique

In this paper,Haar collocation algorithmis developed for the solution of first-order ofHIV infection CD4^(+)T-Cells model.In this technique,the derivative in the nonlinear model is approximated by utilizing Haar functions.The value of the unknown function is obtained by the process of integration.Error estimation is also discussed,which aims to reduce the error of numerical solutions.The numerical results show that the method is simply applicable.The results are compared with Runge-Kutta technique,Bessel collocation technique,LADM-Pade and Galerkin technique available in the literature.The results show that the Haar technique is easy,precise and effective.

CD4+ T-Cell Count, Serum Zinc, Copper and Selenium Levels in HIV Sero-Positive Subjects on ART and ART Naïve Subjects in Port Harcourt, Nigeria

Background: HIV infection results in depletion of immunocompetent cells such as CD4+ T-cells. Trace elements such as Copper, Zinc and selenium are known to be involved in immune function. In recent times, HIV-positive patients are treated with antiretroviral therapy (ART), with significant progress. This study was aimed at evaluating CD4+ T-cells levels, serum Copper, Zinc and Selenium levels in HIV seropositive subjects on ART and ART naive subjects (HIV positive subjects that have not started ART treatment) in Rivers State, Nigeria. Methods: 150 subjects aged 20 to 79 years were recruited after informed consent. 70 subjects were HIV-positive on ART, 30 subjects were HIV-positive ART naïve subjects, while 50 subjects were apparently healthy subjects. Ten (10) milliliters of blood was collected using a standard venipuncture technique from each subject for the analysis of CD4 T-cells using BD fluorescent activated cell sorter (FACSC count), serum Copper and Zinc were analyzed colorimetrically using semi auto-analyzer WP 21E, while selenium was analyzed using atomic absorption spectrophotometer ELICO, SL173. Data generated were analyzed using Graph-Pad Prism version 8.0.2 and p Result: This study revealed a significant reduction in mean zinc, selenium and CD4+ T-cell level respectively (p = 0.0006;0.0001;0.0001) in HIV-Positive subjects on ART and ART naive. There was also a significant increase in mean serum copper level in the HIV-positive subject as compared to control subjects (p = 0.0001). ART treatment improved the CD4+ T cell count and serum levels of selenium and zinc;however, ART did not correct the imbalance. Furthermore, female subjects on ART have a significantly higher CD4+ T-cell count than the males (p Conclusion: Selenium and Zinc deficiency are associated with HIV disease despite the role of ART hence micronutrient supplementation is advised for HIV-positive subjects on ART.

儿童过敏性鼻炎特异性免疫治疗过程中外周血CD4^+调节性T细胞的变化及意义

目的探讨儿童过敏性鼻炎(allergic rhinitis,AR)的发病及特异性免疫治疗(specific immunotherapy,SIT)的治疗机制。方法采用流式细胞术检测56例AR患者SIT治疗前、治疗1年后外周血中CD4+CD25+CD127lo/-Treg表达水平:采用ELISA法检测血清中IL-10、TGF-β1,并与30例健康儿童进行对比。结果 56例AR患儿SIT治疗前外周血中CD4+CD25+CD127lo/-Treg占CD4+T细胞的百分比为(5.36±1.31)%,显著低于对照组(10.23±2.26)%,P<0.05,但SIT治疗1年后其数值为(9.37±2.15)%,与对照组无明显差异。AR患儿治疗前血清中IL-10值为(3.68±1.21)pg/ml,显著低于对照组的(12.37±2.18)pg/ml,P<0.05;TGF-β1表达水平与对照组比较差异无统计学意义。SIT治疗1年后血清中IL-10水平亦与对照组差异不明显(P<0.05);而TGF-β1表达水平分别为(20.16±4.45)pg/ml及(9.27±2.38)pg/ml,其差异有统计学意义(P<0.05)。结论儿童AR患者外周血中CD4+Treg表达水平低,且存在功能缺陷,导致体内诱导免疫耐受机能不足,SIT治疗可以明显调节免疫免疫细胞的功能。

Nocardia cyriacigeorgica infection in a patient with repeated fever and CD4+T cell deficiency:A case report

BACKGROUND Nocardia pneumonia shares similar imaging and clinical features with pulmonary tuberculosis and lung neoplasms,but the treatment and anti-infective medication are completely different.Here,we report a case of pulmonary nocardiosis caused by Nocardia cyriacigeorgica(N.cyriacigeorgica),which was misdiagnosed as community-acquired pneumonia(CAP)with repeated fever.CASE SUMMARY A 55-year-old female was diagnosed with community-acquired pneumonia in the local hospital because of repeated fever and chest pain for two months.After the anti-infection treatment failed in the local hospital,the patient came to our hospital for further treatment.Enhanced computed tomography showed multiple patchy,nodular and strip-shaped high-density shadows in both lungs.A routine haematological examination was performed and showed abnormalities in CD19+B cells and CD4+T cells.Positive acid-fast bifurcating filaments and branching gram-positive rods were observed in the bronchoalveolar lavage fluid of the patient under an oil microscope,which was identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry as N.cyriacigeorgica.The patient’s condition quickly improved after taking 0.96 g compound sulfamethoxazole tablets three times a day.CONCLUSION The antibiotic treatment of Nocardia pneumonia is different from that of common CAP.Attention should be given to the pathogenic examination results of patients with recurrent fever.Nocardia pneumonia is an opportunistic infection.Patients with CD4+T-cell deficiency should be aware of Nocardia infection.

CD4-positive diffuse large B-cell lymphoma:A variant with aggressive clinical potential

CD4 expression is rare in diffuse large B-cell lymphoma(DLBCL), with 4 previously reported cases. Its significance is uncertain. We report five patients with CD4+ DLBCL and one CD4+ primary mediastinal large B-cell lymphoma. Cases were identified by searching the electronic database of the department; each was reviewed. Average age was 56 years. Neoplastic cells expressed CD20(5/6 tested cases). BCL2/BCL6 expression were seen in 3/3 tested cases, suggesting a germinal center origin. Additionally, expression of T-cell antigens CD2 and CD5 was noted in 2/2 and CD7 in 1/1 tested case. CD3 was negative in all. Lymph nodes were commonly involved(67%). Patients received chemotherapy +/- radiation(6/6) and bone marrow transplant(2/6). Average survival was 44.2 mo. CD4 expression in DLBCL raises questions of lineage commitment. CD4+ DLBCL is rare; care should be exercised not to diagnose these as T-cell lymphomas. A subset behaves aggressively.

CD4^(+)T cells produce IFN-I to license cDC1s for induction of cytotoxic T-cell activity in human tumors

CD4^(+)T cells can"help"or"license" conventional type 1 dendritic cells(cDC1s)to induce CD8^(+)cytotoxic T lymphocyte(CTL)anticancer responses,as proven in mouse models.We recently identified cDC1s with a transcriptomic imprint of CD4^(+)T-cell help,specifically in T-cell-infiltrated human cancers,and these cells were associated with a good prognosis and response to PD-1-targeting immunotherapy.Here,we delineate the mechanism of cDC1 licensing by CD4^(+)T cells in humans.Activated CD4^(+)T cells produce IFNβvia the STING pathway,which promotes MHC-I antigen(cross-)presentation by cDC1s and thereby improves their ability to induce CTL anticancer responses.In cooperation with CD40 ligand(L),IFNβalso optimizes the costimulatory and other functions of cDC1s required for CTL response induction.IFN-I-producing CD4^(+)T cells are present in diverse T-cell-infiltrated cancers and likely deliver“help”signals to CTLs locally,according to their transcriptomic profile and colocalization with“helped/licensed”cDCs and tumor-reactive CD8^(+)T cells.In agreement with this scenario,the presence of IFN-I-producing CD4^(+)T cells in the TME is associated with overall survival and the response to PD-1 checkpoint blockade in cancer patients.

Baseline Naive CD4＋ T-cell Level Predicting Immune Reconstitution in Treated HIV-infected Late Presenters

Background：Among HlV-infected patients initiating antiretroviral therapy （ART）,early changes in CD4＋ T-cell subsets are well described.However,HIV-infected late presenters initiating treatment present with a suboptimal CD4＋ T-cell reconstitution and remain at a higher risk for AIDS and non-AIDS events.Therefore,factors associated with CD4＋ T-cell reconstitution need to be determined in this population,which will allow designing effective immunotherapeutic strategies.Methods：Thirty-one adult patients with baseline CD4＋ T-cell count 〈350 cells/mm^3 exhibiting viral suppression after ART initiation were followed in the HIV/AIDS research center of Peking Union Medical College Hospital in Beijing,China,from October 2002 to September 2013.Changes in T-cell subsets and associated determinants were measured.Results：Median baseline CD4＋ T-cell count was 70 cells/mm3.We found a biphasic reconstitution ofT-cell subsets and immune activation：a rapid change during the first 6 months followed by a more gradual change over the subsequent 8 years.Baseline CD4＋ T-cell count 〉200 cells/ mm3 in comparison to CD4＋ T-cell count ≤200 cells/mm3 was associated with more complete immune Reconstitution （77.8% vs.27.3% respectively;P =0.017） and normalized CD4/CD8 ratio.We showed that the baseline percentage of naive CD4＋ T-cell was a predictive marker for complete immune reconstitution （area under receiver operating characteristic curve 0.907）,and 12.4% as cutoffvalue had a sensitivity of 84.6% and a specificity of 88.2%.Conclusions：Baseline naive CD4＋ T-cell percentage may serve as a predictive marker for optimal immune reconstitution during long-term therapy.Such study findings suggest that increasing thymic output should represent an avenue to improve patients who are diagnosed late in the course of infection.

CD4^＋ T-cell dependence of primary CD8^＋ T-cell response against vaccinia virus depends upon route of infection and viral dose

CD4^＋ T-cell help （CD4 help） plays a pivotal role in CD8^＋ T-cell responses against viral infections. However, the role in primary CD8^＋ T-cell responses remains controversial. We evaluated the effects of infection route and viral dose on primary CD8^＋ T-cell responses to vaccinia virus （VACV） in MHC class II^-/- mice. CD4 help deficiency diminished the generation of VACV-specific CD8^＋ T cells after intraperitoneal （i.p.） but not after intranasal （i.n.） infection. A large viral dose could not restore normal expansion of VACV-specific CD8^＋ T cells in i.p. infected MHC II-/- mice. In contrast, dependence on CD4 help was observed in i.n. infected MHC II-/- mice when a small viral dose was used. These data suggested that primary CD8~ T-cell responses are less dependent on CD4 help in i.n. infection compared to i.p. infection. Activated CD8~ T cells produced more I FN-y, TNF-a and granzyme B in i.n. infected mice than those in i.p. infected mice, regardless of CD4 help. IL-2 signaling via CD25 was not necessary to drive expansion of VACV-specific CD8~ T cells in i.n. infection, but it was crucial in i.p. infection. VACV-specific CD8^＋ T cells underwent increased apoptosis in the absence of CD4 help, but proliferated normally and had cytotoxic potential, regardless of infection route. Our results indicate that route of infection and viral dose are two determinants for CD4 help dependence, and intranasal infection induces more potent effector CD8^＋ T cells than i.D. infection.

Early life undernutrition reprograms CD4^+T-cell glycolysis and epigenetics to facilitate asthma

With the support by the National Natural Science Foundation of China,the research team directed by Prof.Huang HeFeng(黄荷风)at Shanghai Key Laboratory of Embryo Original Disease,Institute of Embryo Fetal Original Adult Disease and International Peace Maternity&.Child Health Hospital,School of Medicine,Shanghai Jiao Tong University.

Parameters estimation of HIV infection model of CD4＋ T-cells by applying orthonormal Bernstein collocation method

The HIV infection model of CD4＋ T-cells corresponds to a class of nonlinear ordinary differential equation systems. In this study, we provide the approximate solution of this model by using orthonormal Bernstein polynomials （OBPs）. By applying the proposed method, the nonlinear system of ordinary differential equations reduces to a nonlinear system of algebraic equations which can be solved by using a suitable numerical method such as Newton＇s method. We prove some useful theorems concerning the convergence and error estimate associated to the present method. Finally, we apply the proposed method to get the numerical solution of this model with the arbitrary initial conditions and values. Furthermore, the numerical results obtained by the suggested method are compared with the results achieved by other previous methods. These results indicate that this method agrees with other previous methods.

A numerical method for the solutions of the HIV infection model of CD4＋ T-cells

In this paper, the human immunodeficiency virus （HIV） infection model of CD4＋ T-cells is considered. In order to numerically solve the model problem, an operational method is proposed. For that purpose, we construct the operational matrix of integration for bases of Taylor polynomials. Then, by using this matrix operation and approximation by polynomials, the HIV infection problem is transformed into a system of algebraic equations, whose roots are used to determine the approximate solutions. An important feature of the method is that it does not require collocation points. In addition, an error estimation technique is presented. We apply the present method to two numerical examples and compare our results with other methods.

固体火箭冲压发动机直连试验分析方法研究

阐述了固冲发动机直连试验和试验方法,并根据试验获得的静温/静压/流量等参数提出了试验分析方法,能够获得燃烧效率、比冲效率。在不考虑热力计算误差的条件下,根据试验系统的测试精度,对该方法进行误差分析,表明:(1)通过补燃室尾部静压、静温、流量来换算尾部总压,相对误差较大,应该对尾部总压进行直接测量。(2)用该系统得到的燃烧效率、推力增益比冲、台架推力比冲的相对误差在±3.6%左右,主要误差来源于空气流量、补燃室尾部静压、台架推力,应该对这些参数的测试精度进行严格控制,以减小试验误差。

Treg/Th17 cell balance and phytohaemagglutinin activation of T lymphocytes in peripheral blood of systemic sclerosis patients

AIM To investigate T-cell activation, the percentage of peripheral T regulatory cells(Tregs), Th17 cells and the circulating cytokine profile in systemic sclerosis(SSc).METHODS We enrolled a total of 24 SSc patients and 16 healthy controls in the study and divided the patients as having diffuse cutaneous SSc(dc SSc, n = 13) or limited cutaneous SSc(lc SSc, n = 11). We performed a further subdivision of the patients regarding the stage of the disease-early, intermediate or late. Peripheral venous blood samples were collected from all subjects. We performed flow cytometric analysis of the activationcapacity of T-lymphocytes upon stimulation with PHA-M and of the percentage of peripheral Tregs and Th17 cells in both patients and healthy controls. We used ELISA to quantitate serum levels of human interleukin(IL)-6, IL-10, tissue growth factor-β1(TGF-β1), and IL-17 A.RESULTS We identified a decreased percentage of CD3+CD69+ cells in PHA-stimulated samples from SSc patients in comparison with healthy controls(13.35% ± 2.90% vs 37.03% ± 2.33%, P < 0.001). However, we did not establish a correlation between the down-regulated CD3+CD69+ cells and the clinical subset, nor regarding the stage of the disease. The activated CD4+CD25+ peripheral lymphocytes were represented in decreased percentage in patients when compared to controls(6.30% ± 0.68% vs 9.36% ± 1.08%, P = 0.016). Regarding the forms of the disease, dc SSc patients demonstrated lower frequency of CD4+CD25+ T cells against healthy subjects(5.95% ± 0.89% vs 9.36% ± 1.08%, P = 0.025). With regard to Th17 cells, our patients demonstrated increased percentage in comparison with controls(18.13% ± 1.55% vs 13.73% ± 1.21%, P = 0.031). We detected up-regulated Th17 cells within the lc SSc subset against controls(20.46% ± 2.41% vs 13.73% ± 1.21%, P = 0.025), nevertheless no difference was found between dc SSc and lc SSc patients. Flow cytometric analysis revealed an increased percentage of CD4+CD25-Foxp3+ in dc SSc patients compared to controls(10.94% ± 1.65% vs 6.88% ± 0.91, P = 0.032). Regarding the peripheral cytokine profile, we detected raised levels of IL-6 [2.10(1.05-4.60) pg/m L vs 0.00 pg/m L, P < 0.001], TGF-β1(19.94 ± 3.35 ng/m L vs 10.03 ± 2.25 ng/m L, P = 0.02), IL-10(2.83 ± 0.44 pg/m L vs 0.68 ± 0.51 pg/m L, P = 0.008), and IL-17 A [6.30(2.50-15.60) pg/m L vs 0(0.00-0.05) pg/m L, P < 0.001] in patients when compared to healthy controls. Furthermore, we found increased circulating IL-10, TGF-β, IL-6 and IL-17 A in the lc SSc subset vs control subjects, as it follows: IL-10(3.32 ± 0.59 pg/m L vs 0.68 ± 0.51 pg/m L, P = 0.003), TGF-β1(22.82 ± 4.99 ng/m L vs 10.03 ± 2.25 ng/m L, P = 0.031), IL-6 [2.08(1.51-4.69) pg/m L vs 0.00 pg/m L, P < 0.001], and IL-17 A [14.50(8.55-41.65) pg/m L vs 0.00(0.00-0.05) pg/m L, P < 0.001]. Furthermore, circulating IL-17 A was higher in lc SSc as opposed to dc SSc subset(31.99 ± 13.29 pg/m L vs 7.14 ± 3.01 pg/m L, P = 0.008). Within the dc SSc subset, raised levels of IL-17 A and IL-6 were detected vs healthy controls: IL-17 A [2.60(0.45-9.80) pg/m L vs 0.00(0.00-0.05) pg/m L, P < 0.001], IL-6 [2.80(1.03-7.23) pg/m L vs 0.00 pg/m L, P < 0.001]. Regarding the stages of the disease, TGF-β1 serum levels were increased in early stage against late stage, independently from the SSc phenotype(30.03 ± 4.59 ng/m L vs 13.08 ± 4.50 ng/m L, P = 0.017).CONCLUSION It is likely that the altered percentage of Th17 and CD4+CD25-Fox P3+ cells along with the peripheral cytokine profile in patients with SSc may play a key role in the pathogenesis of the disease.

Lymphocytic esophagitis: Still an enigma a decade later

Lymphocytic esophagitis (LE) is a clinicopathologic entity first described by Rubio et al in 2006. It is defined as peripapillary intraepithelial lymphocytosis with spongiosis and few or no granulocytes on esophageal biopsy. This definition is not widely accepted and the number of lymphocytes needed to make the diagnosis varied in different studies. Multiple studies have described potential clinical associations and risk factors for LE, such as old age, female gender and smoking history. This entity was reported in inflammatory bowel disease in the pediatric population but not in adults. Other associations include gastroesophageal reflux disease and primary esophageal motility disorders. The most common symptom is dysphagia, with a normal appearing esophagus on endoscopy, though esophageal rings, webs, nodularities, furrows and strictures have been described. Multiple treatment modalities have been used such as proton pump inhibitors and topical steroids. Esophageal dilation seems to be therapeutic when dysphagia is present along with esophageal narrowing secondary to webs, rings or strictures. The natural history of the disease remains unclear and needs to be better delineated. Overall, lymphocytic esophagitis seems to have a chronic and benign course, except for two cases of esophageal perforation in the literature, thought to be secondary to this entity.

Unravelling the Functions of Regulatory T Cells during Infection

Accumulating evidences have suggested that Treg have an active role in the regulation of immunity to infection. Treg suppress not only autoimmune responses but also other immune responses for instance, during acute infections, against commensal microbes in inflammatory diseases or during chronic illness. Treg have been shown to limit exacerbated inflammation to avoid collateral tissue damage. Treg are also suggested to provide early protective responses in some viral infections as the permitting timely entry of effector cells in infected tissue. Furthermore, Treg have been shown to contribute to form memory pool after resolution of infection. In this review, we survey and analysis our current knowledge and relative dynamics of Treg in a wide range of infection settings and elaborate the examples in which these cells are of critical importance in conferring tolerance, suppressing pathogenesis, inducing protection and optimizing immunity to eliminate infection.

CTL Response Suppression in Chronic Phase of Infection:A mathematical study

Human immunodeficiency virus(HIV)has had an insightful impact about the state of healthiness of human immune system.Due to great improvement in drug therapy,HIV infections have been reduced by 17%over the past eight years.It has been proved that most effective treatment HAART(Highly Active Anti Retroviral Therapy)mainly controls the diseases progression but it does not eradicate the diseases completely.Reverse Transcriptase Inhibitor drugs specially associated with virus specific Cytotoxic T-Lymphocyte(CTL)that declines with disease progression. CTL responses against AIDS pathogenesis could be potential in the dynamics of virus replication, recognition and clearance of infected cells.In this research article a mathematical model has been proposed on the basis of CTL response suppression in the chronic phase of infection due to presence of virus.We also consider the growth of the virus population from the infected CD4^+T cells budding process and from the other infected cells like macrophages and thymocytes.Our analytical and numerical studies are consistent with existing observations from allied areas.

Does Cyclosporine Down Regulate IL-17 in Cardiac Allograft Vasculopathy?

Background: Cardiac Allograft Vasculopathy (CAV) is characterized by vascular inflammation and intimal proliferation which results in luminal stenosis and myocardial infarction. During vascular inflammation elaboration of several cytokines and differential expression of growth factors have been noted. CAV remains the major threat to long-term graft survival. CD4 and CD8 T-cell subsets play a significant role in the development of transplant rejection. Chronic transplant rejection often leads to development of CAV. A new CD4 effector cell subset that produces IL-17 (Th17) has been shown to be up-regulated in the murine system in the setting of CAV. This study assesses the level of IL-17 in cardiac transplant patients with and without CAV as compared to nontransplanted controls. Methods: Levels of IL-17, IL-6, MCP-1 were measured by ELISA in plasma of four nontransplanted controls, nine cardiac allograft recipients with CAV (HT-GVD) and eight post transplant subjects without a diagnosis of CAV (HT-No GVD). All post transplant patients were immune suppressed with cyclosporine. HT-GVD patients were 1-15 years post transplant while HT-No GVD subjects were 1 - 10 years post transplant. Results: IL-17, MCP-1 and IL-6 were significantly down regulated in HT-GVD subjects compared to the HT-No GVD subjects (p 0.001) but not significant between controls and HT-No GVD (p = ns). Conclusions: A decrease in IL-17 in HT-GVD subjects as compared to HT-No GVD in the presence of cyclosporine treatment could be a consequence of down regulation of IL-6. It is likely that cyclosporine differentially regulates pro inflammatory molecules in the setting of graft vascular disease.

The Effects of Treatment on Serum Hepcidin and Iron Homeostasis in HIV-1-Infected In-dividuals

Background: Hepcidin is the principal regulator of iron absorption and its tissue distribution. Its correlation with iron homeostasis in individuals infected with human immunodeficiency virus type-1 (HIV-1) treated with different regimens of highly active antiretroviral therapy (HAART) was investigated. Methods: Serum hepcidin levels were determined in 448 volunteers. Of these, 372 were HIV-1-infected individuals, and 93 did not receive HAART (ART-na&iuml;ve) while 279 received HAART consisting of a non-nucleoside reverse transcriptase inhibitor (NNRTI-based) and protease inhibitors (PI-based);both were used in association with a nucleoside reverse transcriptase inhibitor (NRTI). Seventy-six additional HIV-1 seronegative individuals were enrolled in the study. The following parameters were quantified: hematological parameters, iron biomarkers and markers of infection (CD4+ and CD8+ T-cells), and HIV-1 RNA (viral load). Results: Serum hepcidin, iron and ferritin levels, as well as the marker of infection, CD4+ T-cells, were significantly lower in the ART-na&iuml;ve group compared with other groups. Additionally, transferrin saturation, iron binding capacity, hemoglobin level and erythrocyte level were not significantly different, and anemia was not observed in the different groups. Conclusions: HIV-1 infection affected serum hepcidin, iron and ferritin levels in the ART-na&iuml;ve group, and the different HAART regimens restored the levels of hepcidin and iron homeostasis in HIV-1-infected individuals who have undetectable HIV-1 RNA levels.

Mifepristone (RU486) Inducing Abortion in a Mouse Model by Regulating Innate and Adaptive Immune Responses

Objective:Mifepristone(RU486),one of the most common medications for artificial abortion,attenuates the immunoregulatory effects of progesterone.However,the specific immune regulatory mechanism of RU486 in abortion remains unknown.We intended to investigate the immunomodulatory effects of RU486 on abortion.Methods:Sixty female mice were divided into the control group(0 mg RU486)and RU486 group(2 mg/kg RU486).The uterus,peripheral blood,and spleen were obtained for isolation of specific cell types.The population and phenotype of immune cells in the decidua,peripheral blood,and spleen were analyzed using flow cytometry.Statistical differences between groups were determined using two-tailed t-test.For all statistical tests,P<0.05 was considered statistically significant.Results:RU486 effectively induced abortion in pregnant mice,with a significantly higher number of decidual macrophages(dMφ)(control group=25.55%±2.467%,RU486 group=19.41%±1.423%;P<0.05),especially the major histocompatibility complex II high subset.No difference in Mφnumber was observed in the spleen or peripheral blood.Moreover,the dMφfrom mice with RU486-induced abortion displayed a remarkable activated phenotype,with increased expressions of inducible nitric oxide synthase,tumor necrosis factor-α,and interleukin(IL)-12 but decreased expressions of arginase-1 and IL-10.We also found elevated levels of decidual CD4+T-cells in the RU486 group that exhibited a higher level of the proinflammatory cytokine interferon-γand a lower level of the anti-inflammatory cytokines,IL-4 and IL-10.Conclusions:We report a new mechanism of RU486-induced abortion via the regulation of innate cell Mφactivation and the adaptive response of CD4+T-cells present in the decidua but not the periphery.

MicroRNA-125b regulates Th17/Treg cell differentiation and is associated with juvenile idiopathic arthritis

Background Juvenile idiopathic arthritis(JIA)is the most common rheumatic disease in childhood driven by aberrant pathways of T-cell activation.T helper 17(Th17)/regulatory T cell(Treg)imbalance plays critical roles in the pathogenesis of arthritis.MicroRNA-125b(miR-125b)was upregulated after the activation of the initial CD4^+T cells,and could regulate the differentiation of CD4^+T cells.However,the effects of miR-125b on Th17/Treg imbalance and differentiation of Th 17/Treg cells remain unknown.Methods In this study,we evaluated the expression of miR-125b in the peripheral blood mononuclear cells(PBMCs)of children with JIA,and the relationship of miR-125b with Th17/Treg imbalance.Then,we used lentivirus vector-mediated overexpression technology to investigate the regulatory function of miR-125b in CD4^+T cells or dendritic cell/CD4^+T co-culture system.Results Decreased miR-125b expression in PBMCs and CD4^+T cells of JIA patients was negatively correlated with the ratio of Th17/Treg cells.It also correlated negatively with retinoic acid receptor-related orphan receptorγt but positively with Forkhead box protein 3 at transcriptional levels.Furthermore,we found that miR-125b overexpression inhibited Th17 cell differentiation,whereas facilitated the differentiation of Treg cells.MiR-125b upregulation led to the decrease of Th 17-secreting cytokines but the increase of the Treg-secreting cytokines.Conclusions Our results demonstrate that miR-125b participated in regulating Thl7/Treg cell differentiation and imbalance in JIA patients.These findings provide novel insight into the critical role of miR-125b in the Th17/Treg imbalance of JIA,and raise the distinct possibility that miR-125b may prove to be a potential therapeutic target for JIA.