Proportion Of Th17 Research Articles

Changes of helper T cell 17/regulatory T cells and cytokines in peripheral blood of rats with acute alcoholic liver injury and clinical significance

Objective To investigate the changes of helper T cell 17 (Th17)/regulatory T cell (Treg) cells and cytokines in peripheral blood of rats with acute alcoholic liver injury and the clinical significance. Methods Thirty-six male SD rats were randomly divided into control group and model group. The animals in the model group were given 30°, 40° or 50° liquor at a dose of 10 ml/kg for 2 consecutive weeks, and those in the control group were given an equal volume of distilled water. The aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin (TBIL) levels in peripheral blood were determined using AST, ALT and TBIL test kits. The liver function damage was evaluated by hematoxylin and eosin (HE) staining. The expression of Th17 and Treg cells were analyzed by flow cytometry. The serum levels of interleukin (IL)-6, IL-17, tumor necrosis factor-α (TNF-α), IL-10 and IL-35 were measured by enzyme linked immunosorbent assay (ELISA). Results As compared with the levels of AST [(130.66±12.07) U/L], ALT [(60.49±6.20) U/L] and TBIL [(30.83±3.22) μmol/L] in control group, the AST [(195.61±20.74) U/L], ALT [(88.16±9.33) U/L] and TBIL (48.54±5.41) μmol/L levels in model group were significantly increased (t=3.419, 3.174 and 4.058 respectively, P<0.05). Pathological staining showed that the liver tissue of the model group was seriously damaged. As compared with the proportion of Th17 [(2.48±0.30)%], Treg [(7.74±0.79)%] and the Th17/Treg ratio (0.33±0.07) in control group, the proportion of Th17 [(5.87± 0.61)%] and Th17/Treg ratio (1.76±0.22) in model group was significantly increased [(5.87± 0.61)%], and the proportion of Treg cells was significantly decreased [(3.25±0.35)%, t=4.331, 4.428 and 5.663 respectively, P<0.01]. As compared with the expression of IL-6 [(28.06±3.03) ng/L], IL-17 [(21.39±2.63) ng/L], TNF-α [(70.56±6.99) ng/L], IL-10 [(25.67±2.42) ng/L] and IL-35 [(33.17±3.25) ng/L] in control group, the levels of IL-6 [(62.81±6.55) ng/L], IL-17 [(52.46±5.40) ng/L] and TNF-α [(161.17±17.32) ng/L] in model group were significantly increased in model group (t=4.220, 4.316, 4.207 and 3.574 respectively, P<0.05), and those of IL-10 [(15.72±1.70) ng/L] and IL-35 [(19.66±2.03) ng/L] were significantly reduced (t=3.618, P<0.05). Conclusion The imbalance of Th17/Treg cells and unusual expression of cytokines may play an important role in acute alcoholic liver injury. Key words: Acute alcoholic liver injury; Lymphocyte subset; Cytokines

Changes in interleukin-27 levels in patients with acute coronary syndrome and their clinical significance.

BackgroundThis study evaluated changes in interleukin (IL)-27 levels in patients with acute coronary syndrome (ACS) and their influence on Th1, Th2, and Th17 cells.MethodsSerum levels of IL-27, IL-4, IL-17, and interferon (IFN)-γ in healthy subjects as well as patients with ACS, including stable angina pectoris (SA), unstable angina pectoris (UA), and acute myocardial infarction (AMI), were determined using an enzyme-linked immunosorbent assay. The proportions of Th1, Th2, and Th17 cells among peripheral blood mononuclear cells (PBMCs), were measured using flow cytometry, after incubation with phorbol myristate acetate (PMA) for 4 h. The proportions of Th1 and Th17 cells among PBMCs in AMI and UA were detected after stimulation with IL-27 or PMA + IL-27 for 4, 8, and 12 h.ResultsSerum levels of IL-27 in patients with AMI and UA were significantly lower than those in SA and control groups, while serum levels of IL-17 and IFN-γ in AMI and UA groups were dramatically increased compared to those in SA and healthy control groups. However, there were no statistically significant differences in serum IL-4. The proportions of Th1 and Th17 cells among PBMCs were statistically significantly higher in the AMI and UA groups than those in the SA and control groups, while there was no statistically significant difference in the proportion of Th2 cells among different groups. For patients with AMI and UA, the effect of co-stimulation of PBMCs with PMA and IL-27 was not significantly different from that of PMA single stimulation, while PMA + IL-27 co-stimulation lowered the Th17 cell proportion significantly compared to PMA single stimulation.DiscussionCompared to SA patients and healthy controls, patients with ACS (AMI + UA) had lower serum levels of IL-27 and higher proportions of PBMC Th1 and Th17 cells, which could be attributed to the inhibitory effects of IL-27 on the proliferation of Th17 cells. These results indicated that IL-27 could be a novel therapeutic target in ACS patients.

Microbiotas from Humans with Inflammatory Bowel Disease Alter the Balance of Gut Th17 and RORγt+ Regulatory T Cells and Exacerbate Colitis in Mice

Microbiota are thought to influence the development and progression of inflammatory bowel disease (IBD), but determining generalizable effects of microbiota on IBD etiology requires larger-scale functional analyses. We colonized germ-free mice with intestinal microbiotas from 30 healthy and IBD donors and determined the homeostatic intestinal Tcell response to each microbiota. Compared to microbiotas from healthy donors, transfer of IBD microbiotas into germ-free mice increased numbers of intestinal Th17 cells and Th2 cells and decreased numbers of RORγt+ Treg cells. Colonization with IBD microbiotas exacerbated disease in a model where colitis is induced upon transfer of naive Tcells into Rag1-/- mice. The proportions of Th17 and RORγt+ Treg cells induced by each microbiota were predictive of human disease status and accounted for disease severity in the Rag1-/- colitis model. Thus, an impact on intestinal Th17 and RORγt+ Treg cell compartments emerges as a unifying feature of IBD microbiotas, suggesting a general mechanism for microbial contribution to IBD pathogenesis.

Gestational Diabetes and T-cell (Th1/Th2/Th17/Treg) Immune Profile

Gestational diabetes mellitus (GDM) is a common pregnancy complication, characterized by insulin resistance and low-grade systemic inflammation with a pro-inflammatory immune system response. Our objective was to study the peripheral Th1, Th2, Th17 and Treg response in GDM compared to normal pregnancy. Th1, Th2, Th17 and Treg subsets was determined by flow cytometry based on staining for specific intracellular cytokines, as well as C-reactive protein (CRP) and total IgE circulating levels. The health status of all offspring was also assessed 6 months post-delivery. A total of 49 Caucasian adult pregnant women were enrolled into a GDM (n=26) and Control (n=23) group. At the third trimester of pregnancy, the GDM group had a higher proportion of Th2, Th17 and Treg cells compared to control. Contrary to the control group, the GDM group exhibited no significant change in the Th1/Th2/Th17/Treg profile postpartum. Furthermore, higher circulating CRP and total IgE levels were noted in the GDM group compared to controls. At the 6-month post-delivery assessment, 30.8% of the offspring from the GDM group were found to have developed atopic dermatitis, food allergy or allergic proctocolitis compared to none from the control group. Compared to an uncomplicated pregnancy, GDM exhibits a significantly different peripheral T-cell profile at the third pregnancy trimester characterized by higher proportion of Th2, Th17 and Treg cells which persist six months post-delivery, while the increased high sensitivity CRP (hsCRP) levels stressed the low-grade inflammatory profile of this disease.

Dasatinib Significantly Enhances the Level of Th1 Cells While Decreases the Level of Treg Cells in Chronic Myeloid Leukemia Patients, and Th1 Can be a Potential Marker for Evaluating the Therapeutic Efficacy and Prognosis

In this study, we evaluate the T cell subtypes by flow cytometry on the chronic myeloid leukemia (CML) patients of our center who have received the treatment with dasatinib (n=10), nolotinib (n=26) or imatinib (n=44) for more than 3 months. We also analyze and correlate these data with the clinical remission situations and prognosis. Results: 1. For the anti-cancer cellular immunity associated Th1 cells: 80% of the patients in dasatinib group, 12.5% of the patients in nilotinib group, 27.5% of the patients in imatinib group have a Th1 proportion (Th1/CD4+ T) higher than the upper limit of normal. The statistical analysis shows that the Th1 proportion in dasatinib group (30.86±9.75%) is significantly higher than that in nilotinib group (17.37±9.35%, p=0.00) and in imatinib group (20.79±9.01%, p=0.00). 2. As for the CD8+ T cell proportion (CD8+ T/Lymphocyte) dasatinib group does not show the statistical difference compared with the nilotinib group and the imatinib group respectively (p=0.24; p=0.09). 3. As for the Th2 cell proportion (Th2/CD4+ T), dasatinib group does not show the statistical difference compared with nilotinib group and imatinib group (p=0.96; p=0.62). 4. The Treg proportion (Treg/CD4+ T) in dasatinib group (1.31±0.10%) is significantly lower than that in nilotinib group (2.65±0.97%, p=0.00) and in imatinib group (2.99±1.40%, p=0.00). 5. When we analyzes all the CML patients with a TKI treatment: (1) In those patients with a Th1 proportion above the upper limit of normal _ 25.8% (n=28), 84.62% of these patients obtain CCyR (complete cytogenetic response), 71.43% of these patients obtain MMR (major molecular response ), and 71.43% of these patients obtain MR4.5; (2) In those patients with a Th1 proportion in the normal range _ 11.8-25.8% (n=45), 90.7% of these patients obtain CCyR, 75.56% of these patients obtain MMR, and 75.56% of these patients obtain MR4.5; (3) In those patients with a Th1 proportion below the lower limit of normal _ 11.8% (n=21), 57.14% of these patients obtain CCyR, 47.62% of these patients obtain MMR, and 47.62% of these patients obtain MR4.5. The patients in the high Th1 level or normal Th1 level groups exhibit deeper remission level, which indicates lower risk of disease progression, higher chance for treatment-free and better prognosis. Conclusion: The data of our center indicates that during the TKI treatment for CML patients, the higher or normal level of Th1 may become a potential candidate marker to be monitored, so as to predict the better therapeutic efficacy and prognosis besides CCyR, MMR, and MR4.5. Dasatinib can significantly improve the anti-cancer immunity associated markers compared with nilotinib and imatinib, and this may be the mechanism of dasatinib to bring good therapeutic efficacy and prognosis. DisclosuresNo relevant conflicts of interest to declare.

Preoperative Th1/Th2 and related cytokines: Prediction value in postoperative febrile UTI after ureteroscopy in patients with ureteral calculi.

The topic of whether preoperative Th1/Th2 cells and their related factors have a predictive value for postoperative febrile urinary tract infection (UTI) in patients with ureteral calculi has not been explored. The objective of this study was to investigate the role of preoperative Th1/Th2 cells and related cytokines in the prediction of postoperative febrile UTI after ureteroscopy in patients with ureteral calculi. One hundred sixty patients who underwent ureteroscopic pneumatic lithotripsy in the Affiliated Hospital of Hangzhou Normal University (China) were recruited and divided into febrile UTI group (n = 78) and non-UTI group (n = 82). Flow cytometry was used to detect the proportions of Th1 and Th2 cells (Th1% and Th2%). Detection of Th1/Th2 cell-related cytokines was conducted using enzyme-linked immunosorbent assay (ELISA). Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to measure the expression of T-bet and GATA3. Compared with patients in non-UTI group, those in febrile UTI group had significantly increased proportions of Th2 cells, levels of Th2 cytokines (interleukin (IL)-4, IL-10 and IL-5), and mRNA expression of Th2-associated transcription factor GATA3 (all p < 0.05). In addition, the Th1/Th2 ratio of febrile UTI group was significantly lower than that of non-UTI group (p < 0.001). Receiver operating characteristic (ROC) curve analysis showed that the accuracy rate of Th2%, Th1/Th2 ratio, and IL-4, IL-10 and IL-5 levels for the diagnosis of postoperative febrile UTI in patients with ureteral calculi was 90.63%, 85.00%, 72.50%, 87.50%, and 91.88%, respectively, and their combined diagnostic sensitivity was 97.4% with specificity as high as 100%. Perioperative Th2 dominance was correlated with the risk of postoperative febrile UTI after ureterscopy in patients with ureteral calculi, which can provide clinical guidance for the development of individualized treatment.

Sulfatides ameliorate experimental autoimmune neuritis by suppressing Th1/Th17 cells

Sulfatides have immunomodulatory functions, and play protective roles in multiple autoimmune diseases. In the present study, we showed that sulfatides ameliorated experimental autoimmune neuritis in Lewis rats induced with bovine peripheral myelin, which was associated with decreased proportions of Th1 and Th17 cells. Furthermore, compared control group, cells from sulfatide-treated rats exhibited lower potential in proliferation and IL-17 secretion in the presence of BPM or ConA in vitro. Moreover, sulfatides also reduced the proportions of NK and NKT cells. In summary, our study indicated that sulfatides might become a new therapeutic agent in Guillain-Barré syndrome in the future.

T cells in IgA nephropathy: role in pathogenesis, clinical significance and potential therapeutic target

BackgroundImmunoglobulin A nephropathy (IgAN), the most frequent cause of primary glomerulonephritis worldwide, is an autoimmune disease with complex pathogenesis. In this review, we focus on T cells and summarize knowledge about their involvement in pathophysiology and treatment of IgANMethodsWe reviewed the literature for (1) alterations of T cell subpopulations in IgAN, (2) experimental and clinical proofs for T cells’ participation in IgAN pathogenesis, (3) clinical correlations with T cell-associated alterations, and (4) influence of drugs used in IgAN therapy on T cell subpopulations.ResultsWe found that IgAN is characterized by higher proportions of circulatory Th2, Tfh, Th17, Th22 and γδ T cells, but lower Th1 and Treg cells. We discuss genetic and epigenetic makeup that may contribute to this immunological phenotype. We found that Th2, Th17 and Tfh-type interleukins contribute to elevated synthesis of galactose-deficient IgA1 (Gd-IgA1) and that the production of anti-Gd-IgA1 autoantibodies may be stimulated by Tfh cells. We described the roles of Th2, Th17, Th22 and Treg cells in the renal injury and summarized correlations between T cell-associated alterations and clinical features of IgAN (proteinuria, reduced GFR, hematuria). We detailed the impact of immunosuppressive drugs on T cell subpopulations and found that the majority of drugs have nonoptimal influence on T cells in IgAN patients.ConclusionsT cells play an important role in IgAN pathogenesis and are correlated with its clinical severity. Clinical trials with the drugs targeting the reported alterations of the T-cell compartment are highly desirable.

Oligo-fucoidan improved unbalance the Th1/Th2 and Treg/Th17 ratios in asthmatic patients: An ex vivo study.

An imbalance in the helper T cells (Th)1/Th2 and regulatory T cells (Tregs)/Th17 ratios is believed to play a key role in asthmatic inflammatory responses. Fucoidan reportedly reduces the production of inflammatory factors. Nutritional intervention is an important tool in decreasing the severity of asthmatic disease. This study aimed to investigate the beneficial roles of oligo-fucoidan in balancing the T cell subtype ratios and reducing airway inflammation ex vivo. Peripheral blood mononuclear cells (PBMCs) were collected from 30 asthmatic subjects and 15 healthy subjects. Harvested PBMCs were stimulated and treated with or without oligo-fucoidan (100 or 500 µg/ml) for 48 h. Cell surface and intracellular cytokine markers were examined by flow cytometry. The pro-inflammatory factors in plasma and culture supernatants were measured using ELISA kits. We found that oligo-fucoidan increases the proportion of Th1 and Treg cells, but did not affect the proportion of Th2 and Th17 cells. Oligo-fucoidan also increased the levels of interferon-γ and interleukin-10. Thus, we concluded that oligo-fucoidan might improve the imbalance in Th1/Th2 and Treg/Th17 ratios to reduce airway inflammation, which could be a potential adjuvant therapy for allergic asthma.

Comparative Mid-term Follow-up Study of Primary Total Hip Arthroplasty with Metal-on-metal and Metal-on-polyethylene Bearings.

To compare mid-term clinical results of total hip arthroplasty (THA) with metal-on-metal (MoM) and metal-on-polyethylene (MoP) bearings and to evaluate the biological safety of the two kinds of prostheses. Thirty-two patients who received a primary THA with an MoM articulation between January 2008 and December 2010 were selected to form the MoM group retrospectively. The MoP group consisted of 32 patients who received a THA with an MoP prosthesis during the same period. Clinical assessments, imaging examinations, laboratory tests, and metal ion concentration detections were conducted on each patient. Another 32 healthy volunteers were recruited as the control group. Twenty-seven patients in the MoM group and 28 patients in the MoP group completed the follow-up, with a mean follow-up time of 74.6 and 75.9 months, respectively. The mean Harris score at the latest follow-up was 91.5 ± 5.1 in the MoM group versus 88.9 ± 4.0 in the MoP group (P = 0.22). The MoM group showed a better range of motion in flexion, abduction, and external rotation. Co and Cr levels in the MoM group were 2.5-fold and 2.0-fold of these in the MoP group. A mild change of liver function was observed in both groups, while the values of renal function and humoral immunity stayed static. Elevated proportions of Th1 and Th17 cells and decreased proportion of Th2 cells were observed in the MoM group. The occurrence rate of pseudotumors in the MoM and MoP groups was 40.74% ± 9.45% and 14.28% ± 6.61%, respectively (P < 0.05). At the mid-term follow-up, clinical results were satisfied in both groups. MoM prosthesis could result in elevated serum metal ion levels and there is a higher risk of pseudotumor. Long follow-up is needed to evaluate the safety of MoM prostheses.

1,25-Dihydroxyvitamin D3 modulates T cell differentiation and impacts on the production of cytokines from Chinese Han patients with early rheumatoid arthritis.

To study the effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on the differentiation of T cells and the levels of cytokines in patients with early rheumatoid arthritis (eRA). The levels of Th1, Th2, Th17, and Treg cells were detected with BDFACS Calibur flow cytometer. The expression of IFN-ɤ, TNF-α, IL-2, IL-4, IL-6, IL-10, IL-17, and IL-22 was examined in 54 patients with eRA using a cytometric bead array (CBA). After 72h of incubation of PBMCs from eRA patients with 1,25(OH)2D3, the levels of IFN-ɤ, TNF-α, IL-2, IL-6, and IL-17 significantly decreased compared to those of the control. 1,25(OH)2D3 had no significantly impact on the levels of IL-4, IL-10, and IL-22. The proportion of Th17 and the ratio of Th17/Treg significantly decreased in 1,25(OH)2D3-treated groups compared to those of the control. 1,25(OH)2D3 had no significantly impact on the proportion of Th1, Th2, Treg, and the ratio of Th1/Th2. Although no statistically significant difference was observed, proportion of Th1 was decreased after 1,25(OH)2D3 treatment compared with anti-CD3/CD28 only. The present study demonstrated that 1,25(OH)2D3 inhibited the synthesis of specific cytokines: Th1 (IFN-ɤ) and Th17 (IL-17, IL-22, IL-6, TNF-α) might upregulated Th2 cytokine (IL-4), which indicated the possible immunoregulatory roles and bone-sparing effects of 1,25(OH)2D3 in eRA through modulation of the Th1 and Th17 cytokine balance.

Detailed endometrial immune assessment of both normal and adverse reproductive outcome populations.

Using a comprehensive flow cytometric panel, do endometrial immune profiles in adverse reproductive outcomes such as repeat implantation failure (RIF) and repeat pregnancy loss (RPL) differ from each other and male-factor controls? Six-hundred and twelve patients had an endometrial biopsy to assess the immunophenotype. History on presentation was used to subdivide the population into recurrent implantation failure (RIF) [n = 178], recurrent pregnancy loss (RPL) [n = 155], primary infertility [n = 130] and secondary infertility [n = 114]. A control group was utilised for comparative purposes [n = 35] and lymphocyte subpopulations were described. Distinct lymphocyte percentage differences were noted across the populations. Relative to controls and RPL, patients with a history of RIF had significantly raised uterine NKs (53.2 vs 45.2 & 42.9%, p < 0.0001). All sub-fertile populations had increased percentage peripheral type NKs (p = 0.001), and exhibited increased CD69+ activation (p = 0.005), higher levels of B cells (p < 0.001), elevated CD4:CD8 ratio (p < 0.0001), lower T-regs (p = 0.034) and a higher proportion of Th1+ CD4s (p = 0.001). Patient aetiology confers some distinct findings, RPL; pNK, Bcells and CD4 elevated; RIF; uNK and CD56 raised while CD-8 and NK-T lowered. Flow cytometric endometrial evaluation has the ability to provide a rapid and objective analysis of lymphocyte subpopulations. The findings show significant variations in cellular proportions of immune cells across the patient categories relative to control tissue. The cell types involved suggest that a potential differential pro-inflammatory bias may exist in patients with a history of adverse reproductive outcomes. Immunological assessment in appropriate populations may provide insight into the underlying aetiology of some cases of reproductive failure.

The cholinergic anti-inflammatory pathway ameliorates acute viral myocarditis in mice by regulating CD4+ T cell differentiation

ABSTRACT Many studies have found that abnormalities in the proportion and differentiation of CD4+ T cells (Th cells) are closely related to the pathogenesis of viral myocarditis (VMC). Our previous research indicates that the cholinergic anti-inflammatory pathway (CAP) attenuates the inflammatory response of VMC and downregulates the expression of cytokines in Th1 and Th17 cells. This suggests that the cholinergic anti-inflammatory pathway likely attenuates the inflammatory response in VMC by altering Th cell differentiation. The aim of this study is to investigate the effect of CAP on CD4+ T cell differentiation in VMC mice. CD4+ T cells in the spleen of VMC mice were obtained and cultured in the presence of nicotine or methyllycaconitine (MLA). Cells were harvested and analyzed for the percentage of each Th cell subset by flow cytometry and transcription factor release by Western blot. Then, we detected the effect of CAP on the differentiation of Th cells in vivo. Nicotine or MLA was used to activate and block CAP, respectively, in acute virus-induced myocarditis. Nicotine treatment increased the proportion of Th2 and Treg cells, decreased the proportion of Th1 and Th17 cells in the spleen, reduced the level of proinflammatory cytokines, and attenuated the severity of myocardium lesions and cellular infiltration in viral myocarditis. MLA administration had the opposite effect. Our result demonstrated that CAP effectively protects the myocardium from virus infection, which may be attributable to the regulation of Th cell differentiation.

Rhubarb Peony Decoction ameliorates ulcerative colitis in mice by regulating gut microbiota to restoring Th17/Treg balance

Ethnopharmacology relevanceRhubarb Peony Decoction (RPD) is a formula of traditional Chinese medicine chronicled in Jin Gui Yao Lve, commonly used to treat ulcerative colitis (UC). However, the underlying mechanism of RPD treating UC remains elusive. In our study, we investigated the therapeutic efficacy of RPD and potential mechanism involved in inhibiting dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. MethodsThe colitis was induced by DSS in mice for 5 days and estimated body weight loss, disease activity index (DAI) and colon length. Histological changes were observed by H&E staining. The number and abundance of gut mircrobiota were measured with 16 S rDNA sequencing. GC-MS was used to detect the concentration of short chain fatty acids (SCFAs) in cecum. Flow cytometry analyzed the proportion of Th17 and Treg cells in mesenteric lymph nodes (MLNs). IL-17A and Foxp3 in colon were determined by immunohistochemical analyses. The level of cytokine was determined by Multi-Analyte Flow Assay Kit. ResultsAdministration of RPD significantly alleviated the pathological changes of UC mice, involving rescued the inflammation-related reduction of colon length, ameliorated body weight loss and damaged tissue. In addition, RPD altered the gut microbiota, involving restored α diversity, increased significantly the abundance of Firmicutes and Actinobacteria, decreased the Proteobacteria and Bacteroidetes. Furthermore, the number of Butyricicoccus pullicaecorum, a butyrate-producing bacterium, were augmented obviously by RPD. Besides, RPD restored the content of SCFA in intestinal tract. Additionally, the proportion of Th17 cells and Treg cells in mesenteric lymph nodes, likewise, the expression of IL-17A and Foxp3 in colon were regulated by RPD, contributing to the restoration of Th17/Treg balance. Moreover, RPD significantly decreased the level of IL-6, TNF-α, IFNγ, IL-10, IL-17A, IL-21, IL-22 in colon, simultaneously increased Treg-related cytokine TGF-β at dose-dependently. ConclusionsThese results demonstrated that RPD had effect on ulcerative colitis, which was related to regulating gut microbiota, especially Butyricicoccus pullicaecorum, and SCFAs to restore the gut Th17/Treg homeostasis.

An imbalance in the T-helper phenotypes displayed by senescent CD4+CD28null T cells is associated with erosive arthritis (rhupus syndrome) in systemic lupus erythematosus.

The objective was to assess the proportion of Th1, Th2 and Th17 phenotypes in senescent CD4+CD28null cells from patients with systemic lupus erythematosus (SLE) and its association with the pattern of joint involvement. This cross-sectional study was performed in SLE patients with erosive arthritis (rhupus) or nondeforming, nonerosive arthritis. Total CD4+CD28null cells as well as the proportion of these cells expressing T-bet, GATA3 or RORγt were analyzed by color-flow cytometry. Serum osteopontin levels were measured by ELISA. Eighteen SLE patients (nine with rhupus and nine with nonerosive arthritis) were studied. The percentage of CD4+CD28null/CD4+ cells (17.7%, 10.3-25.0% versus 9.4%, 8.1-22.4%; P = 0.386) as well as the osteopontin levels (5800, 5,134-5995 pg/ml versus 5578, 5171-5717 pg/ml; P > 0.05) were similar in both groups. A higher percentage of CD4+CD28nullT-bet+ cells (42.8%, 33.5-53.4% versus 30.0%, 23.3-34.2%) but a lower percentage of CD4+CD28nullGATA3+ cells (3.1%, 1.7-5.6% versus 6.2%, 2.6-18.4%) was observed in patients with rhupus than in their counterparts ( P = 0.016). The frequency of CD4+CD28nullRORγt+ cells was similar between groups. In patients with rhupus, senescent CD4+CD28null cells are preferentially polarized to a Th1 phenotype, whereas this is partial towards Th2 in lupus patients with a nonerosive arthritis pattern.

The changes of expressive levels of IL-17A, STAT3, and RORγt in different invasive pulmonary aspergillosis mice.

BackgroundT helper 17 (Th17) lymphocytes play an important role in Aspergillus adaptive immune response against Aspergillus fumigatus, but there is little attention focused on the different types of immunosuppressive models in which invasive pulmonary aspergillosis (IPA) develops. In addition, the expression levels of signal transducer and activator of transcription 3 (STAT3)/retinoic acid-related orphan nuclear receptor gamma (RORγt)/interleukin (IL)-17A signaling pathway, which is involved in the regulation of Th17 cells, as well as whether there are differences between two types of IPA mice models, remain unknown.Materials and methodsSix to eight weeks old female BALB/c mice were treated with cortisone acetate or cyclophosphamide to establish the immunosuppressive mice models, and then, A. fumigatus inoculum was injected to form the IPA groups and sterile saline was injected to form the control groups. Flow cytometry was performed to measure the proportion of Th17 cells in CD4+ T cells in the peripheral blood, spleen, and lung of the mice. The expression of IL-17A, RORγt, and STAT3 mRNA was detected by real-time polymerase chain reaction. Concentrations of IL-6 in the plasma and bronchoalveolar lavage fluid were measured by enzyme-linked immunosorbent assay.ResultsThe proportion of Th17 in the peripheral blood and lung tissue in neutropenic IPA mice showed a more significant increase than in non-neutropenic IPA mice (P<0.01). The IL-6 protein also showed the same trend in plasma and bronchoalveolar lavage fluid (P<0.01). Compared with the control groups, the expression of IL-17A at mRNA level in the lung was significantly increased, while RORγt/STAT3 mRNA was significantly decreased in the IPA groups (P<0.01).ConclusionThe expression of RORγt and STAT3 mRNA in the lung tissue in both groups was significantly decreased. IL-17 may play a negative role in the defense against Aspergillus through uprating IL-6.

Correlations between the T helper cell 17/regulatory T cells balance in peripheral blood of patients with oral lichen planus and clinical characteristics

This study aimed to investigate the ratio of T helper cell 17 (Th17) and regulatory T cells (Treg) in peripheral blood of oral lichen planus (OLP) and explore the pathogenesis of its possible role and significance. The peripheral blood samples were obtained from 33 patients with OLP (15 cases of reticular OLP and 18 cases of erosive OLP) and 17 healthy controls. The percentages of Th17 and Treg cells were detected by flow cytometry (FCM). Real-time fluorescence quantitative polymerase chain reaction (qPCR) technique was used to detect the expression levels of retinoid-related orphan nuclear receptor γt (RORγt) and forkhead box 3 (Foxp3). The proportions of Th17, Treg cells, and their transcription factors (RORγt and Foxp3) in OLP were higher than those in the control groups (P<0.05). By contrast, in Treg cells and Foxp3, no significance was observed between erosive OLP and reticular OLP. Th17/Treg ratio increased in OLP. This ratio was significantly increased in erosive OLP compared with those in the control groups and reticular OLP (P<0.01). Nevertheless, no significance was noted between reticular OLP and control groups. Statistical analysis demonstrated positive correlations among Th17 cells, Th17/Treg, and clinical characteristics (r=0.66, P=0.00; r=0.66, P=0.00; r=0.52, P=0.00; r=0.50, P=0.00). Positive correlations also existed between Th17 and Treg cells (r=0.39, P=0.03). Th17 cells, Treg cells, and their ratios all increased in the peripheral blood of OLP. Moreover, the imbalance inTh17/Treg may play a role in the pathogenesis of erosive OLP.

Switched memory B cells promote alveolar bone damage during periodontitis: An adoptive transfer experiment

Periodontitis is a bacteria-induced disease that often leads to alveolar bone damage. We sought to determine the role and mechanism of switched memory B cells in alveolar bone destruction during periodontitis. Sensitized B cells were sorted and cultured, then their expression of receptor activator for nuclear factor-κB ligand (RANKL), interleukin-6 (IL-6), and interleukin-12 (IL-12) was detected. Using these cells, we prepared adoptive transfer models in which we induced periodontitis. We found that switched memory B cells produced more RANKL in terms of both protein and mRNA levels than other subpopulations. Switched memory B cells expressed more IL-6 and IL-12 mRNA than other subpopulations, but differences in respective protein levels were not significant. Moreover, we found that switched memory B cell transfer resulted in increased alveolar bone loss and periodontal osteoclastogenesis. Moreover, switched memory B cell transfer increased the proportion of Th1 and Th17 cells as well as the expression of RANKL, osteoprotegerin (OPG), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-1β, IL-6, IL-17A in gingiva, and cervical lymph nodes (CLNs). The outcomes of the present study indicate that switched memory B cells regulate alveolar bone homeostasis via enhancing cytokine expression and increasing proliferation of Th1 and Th17 cells.

MicroRNA-155 regulates cervical cancer via inducing Th17/Treg imbalance.

To explore the effect of microRNA-155 on cervical cancer and its underlying mechanism. Peripheral blood and cervical cancer tissues were collected. We used quantitative Real-time polymerase chain reaction (qRT-PCR) to detect expressions of microRNA-155, SOCS1, Th17-related genes (RORγt, IL-17A, IL-21, and IL-22), and Treg-related genes (foxp3, TGF-β, IL-10, and IL-35) in peripheral blood and cervical cancer tissues. Western blot was used to detect protein expressions of RORγt and foxp3. The proportions of Th17 and Treg cells in CD4+ T cells were measured by flow cytometry. Moreover, IL-17 expression was detected by enzyme-linked immunosorbent assay (ELISA). MicroRNA-155 was overexpressed in peripheral blood and cervical cancer tissues of patients with cervical cancer compared with those of normal controls. Th17-related transcription factors and cytokines in cervical cancer tissues were remarkably elevated than those of normal controls, including RORγt, IL-17, and IL-6. Treg-related transcription factors and cytokines obtained the similar results. Besides, the proportion of Th17 cells in CD4+ T cells was higher in cervical tissues than that of normal controls. In vitro experiments suggested that overexpressed microRNA-155 can inhibit the expression of target gene SOCS1, promote the differentiation of Th17 and increase levels of IL-17, RORγt, and STAT3. MicroRNA-155 is involved in the occurrence and progression of cervical cancer via inhibiting SOSC1 expression and inducing Th17/Treg imbalance.

Changes in Th17 cells function after nanocurcumin use to treat multiple sclerosis

BackgroundMS is a chronic inflammatory disease that causes to brain inflammation and Th17 cells are considered to be important in multiple sclerosis pathogenesis. In the current study, we aimed to identify nanocurcumin effects on Th17 cells frequency, cytokines secretion, and expression of transcription factor of patients with relapsing-remitting multiple sclerosis (RRMS). MethodsIn this study we investigated frequency of Th17 lymphocytes; the expression of transcription factor, associated cytokines and the concentration of them in 35 healthy controls, and from 25 patients at baseline and after 6 months of nanocurcumin treatment and also from 25 patients whose received placebo by flowcytometry, real-time PCR and ELISA, respectively. ResultsOur analysis revealed that the proportions of Th17 were increased dramatically, along with increases in the levels of IL-17A, IL-23, and RORγt expression in MS patients in compared with healthy control group. Post-treatment evaluation of the nanocurcumin group revealed a significant decrease in Th17 associated parameters such as Th17 frequency (p = 0.029), expression levels of RORγt (p < 0.0001) and IL-17 (p = 0.0044) and also secretion level of IL-17 (p = 0.0011), but IL-23 mRNA expression levels and IL-23 concentration were not influenced by nanocurcumin. However, in the placebo group there is no significant changes in these factors. ConclusionOur study suggests that the increase in proportion of Th17 cells might contribute to the pathogenesis of RRMS. The results of the current work indicated that nanocurcumin is able to restore the dysregulated of Th17 cells in MS patients.