Th17 Cells In Peripheral Blood Research Articles

Elevated Circulating CD4+CD25-Foxp3+ Regulatory T Cells in Patients with Nonsmall Cell Lung Cancer.

Purpose: CD4+CD25+Foxp3+ regulatory T (Treg) cell-mediated immunosuppression has been implicated as a crucial mechanism of tumor immune cell escape in nonsmall cell lung cancer (NSCLC). However, little is known concerning the specific role of CD4+CD25-Foxp3+ Treg cells in NSCLC. The aim of this study was to investigate the frequency of circulating CD4+CD25-Foxp3+ Treg cells and their role in NSCLC. Methods: The frequencies of Treg, T helper (Th)1, Th2, and Th17 cells in peripheral blood were separately measured in 36 NSCLC patients and 20 healthy controls (HCs) using flow cytometry. Serum cytokine concentrations were determined using cytometric bead arrays. Results: The frequencies of circulating CD4+CD25+ T cells and CD4+CD25+Foxp3+ and CD4+CD25-Foxp3+ Treg cells were significantly higher in advanced-stage NSCLC patients compared with patients with limited-stage NSCLC. The frequencies of circulating CD4+CD25+Foxp3+ and CD4+CD25-Foxp3+ Treg cells were negatively correlated with interleukin (IL)-17, but positively correlated with serum IL-10 levels. In addition, the Th17/CD4+CD25-Foxp3+ Treg cell ratios were negatively correlated with serum cytokeratin 19 fragment (CYFRA 21-1) concentrations in patients with NSCLC. Moreover, coculturing CD4+CD25-Foxp3+ Treg cells and CD14+ monocytes in vitro resulted in a higher frequency of CD206+CD14+ M2-like monocytes compared with CD14+ monocytes. Conclusions: Elevated circulating CD4+CD25-Foxp3+ Treg cells may be involved in the pathogenesis of NSCLC.

Combination of L-Arginine and L-Norvaline protects against pulmonary fibrosis progression induced by bleomycin in mice

Pulmonary fibrosis (PF) progression may be involved with arginine (Arg) metabolism and immune balance. The present study aimed to explore the effects of L-Arginine (L-Arg) and L-Norvaline (L-Nor) on bleomycin (BLM)-induced PF in mice, meanwhile, and observe dynamic changes of Arg metabolism, immune balance and crosstalk between them in PF progression. Followed intratracheal instillation of BLM or saline, Kunming mice were treated orally with saline, L-Arg, L-Nor and L-Arg + L-Nor three times a day. And the mice were sacrificed on Day 3, 14 and 28 after treatment. Changes of body weight, lung index, lung hydroxyproline and histopathology were analyzed to evaluate the PF degree. Peripheral blood Arg, Citrulline (Cit), Ornithine (Orn) and Proline (Pro), lung NO, NOS and arginase were analyzed to evaluate the Arg metabolism. Peripheral blood Tregs, Th17 and γδT cells were analyzed to evaluate the immune balance. Our data showed that combination of L-Arg and L-Nor dynamically reversed the weight loss, decreased lung index and hydroxyproline, and improved lung histopathological damages induced by BLM. The combination dynamically and significantly rectified Tregs, Th17, γδT and Tregs/Th17 abnormal changes. Meanwhile, these disorders of peripheral blood Arg, Cit, Orn, Pro, Orn/Cit and Pro/Orn, and lung NO, iNOS and TNOS were also improved accordingly. These results demonstrated that combination of L-Arg and L-Nor had inhibitory effects on BLM-induced PF progression, possibly due to their corrective action on immune imbalance, Arg metabolism disorder and crosstalk abnormality in the progression of PF.

Correlation between CTL and Th1 cell proportion in peripheral blood of liver transplantation recipients and the success of hepatitis B vaccination

Objective: To investigate the correlation between the proportion of CTL and Th1 cells in peripheral blood of liver transplant recipients and the success of hepatitis B vaccination. Methods: The subjects of this study were liver transplantation recipients with chronic HBV-related liver diseases in Organ transplantation institute of the third medical center of PLA general hospital. Subjects were randomly divided into two groups for prospective study. In the rapid group, one dose of 40 μg hepatitis B vaccine was administered at 0, 1, 2and 3 months, and one dose of 20 μg hepatitis B vaccine was administered at 4, 5 and 6 months. In the rapid-enhanced group, one dose of 40 μg hepatitis B vaccine was administered at 0, 1, 2 and 3 months, and one dose of 60 μg hepatitis B vaccine was administered at 4, 5 and 6months. Compare and analyze the success rate of inoculation, the titer of hepatitis B surface antibody (anti-HBs), the proportion of CTL cells in CD8(+)T cells and Th1 cells in CD4(+)T cells. Correlation analysis was performed for CTL and Th1 cells and anti-HBs, Observe the safety of vaccination. Results: The inoculation success rate, anti-HBs growth rate, CTL cell percentage increase and Th1 cell percentage increase in the rapid enhancement group were all higher than those in the rapid enhancement group, and the differences were statistically significant, they were 38.3% (23/60) vs 21.7% (13/60) (P=0.046), 91.3(72.5,124.2) vs 22.1(12.4, 31.6) (P=0.001), 1.4(0.8,1.9) vs 0.4(0.2,1.4) (P=0.001) and 7.4±2.6 vs 5.6±3.7 (P=0.001) respectively. The percentage increase of CTL cells and Th1 cells in the successful group was greater than that in the non-successful group, and the difference was statistically significant. They were 1.9(1.4,2.5) vs 0.1(0.0,1.1) (P=0.024) and 9.6±3.1 vs 2.4±2.0 (P<0.001). There was no significant correlation between anti-HBs increase (105.5±37.1) and CTL increase 1(0,3) (P=0.099), while there was significant positive correlation with Th1 increase 7(2,11) (P<0.001). No rejection reaction occurred during the study period, and there was no special abnormal change in the safety index. Conclusion: Reasonable increase of vaccine dose can up-regulate Th1 cell expression and promote the generation of anti-HBs.

Polysaccharide from Radix Codonopsis has beneficial effects on the maintenance of T-cell balance in mice

Immunity due to immune balance contributes to disease prevention and treatment. Radix Codonopsis polysaccharide (RCP) is isolated from the root of the Chinese herb Codonopsis pilosula. Previous studies have indicated that RCP has immunomodulatory activities; however, the effects of RCP on immunity, especially immune balance, are still largely unknown. In the present study, we investigated the effects of RCP on T-cell balance in mice. The mice were pretreated intragastrically with or without RCP for 15 days and injected with hydrocortisone on days 10–15 to disturb the immune system. The spleen and thymus were weighed and used to calculate immune organ indexes. The percentages of CD4+ T cells, CD8+ T cells, Th1 cells, Th2 cells, regulatory T cells (Tregs) and Th17 cells in peripheral blood were assayed by flow cytometry. Pro-inflammatory and anti-inflammatory cytokines, TNF-α, IL-1β and IL-10, in serum were determined by enzyme-linked immunosorbent assay (ELISA) kits. The results showed that RCP pretreatment could maintain the homeostasis of CD8+ T cells, Tregs, Th17 cells, TNF-α, IL-1β and IL-10 in hydrocortisone-treated mice. Furthermore, RCP pretreatment maintained the immune balance of CD4+/CD8+ T cells, Th1/Th2 cells, Tregs/Th17 cells, IL-10/TNF-α and IL-10/IL-1β. Taken together, RCP pretreatment had beneficial effects on the maintenance of T-cell balance against hydrocortisone disturbance in mice and potential to be developed into novel functional food.

Impact of HIV-ART on the restoration of Th17 and Treg cells in blood and female genital mucosa

The aim of this study was to evaluate the effectiveness of antiretroviral treatment (ART) on the proportion and functions of Th17 and Treg cells in peripheral blood and female genital tract (FGT) respectively. To this aim, samples from 41 HIV-neg, 33 HIV+ ART-naïve and 32 HIV+ ART+ subjects were obtained. In peripheral blood, altered Th17 and Th17/Treg proportions were normalized in HIV+ ART+, but certain abnormal Treg and activated T-cell proportions were still observed. In FGT, abnormal patterns of secretion for Th17-related cytokines were observed in cervical mononuclear cells (CMCs) from HIV+ women, even in those from HIV+ ART+, compared to the HIV-neg group. Moreover, these altered patterns of secretion were associated with diminished levels of CXCL5 and CXCL1 chemokines and with an immunoregulatory skew in the CCL17/CCL20 ratio in ectocervix samples of these women. Finally, ART did not restore proportions of Th17-precursor cells with gut-homing potential in PBMCs, and positive correlations between these cells and the levels of IL-17F and IL-21 production by CMCs may suggest that a better homing of these cells to the intestine could also imply a better restoration of these cells in the female genital tract. These results indicate that antiretroviral treatment did not restore Th17-related immune functions completely at the female mucosal level.

Role of Th9, Th17, Treg Cells levels and IL-9, IL-17 and TGF-β Expression in Peripheral Blood of Patients with ITP in Pathogenesis of ITP

To detect the levels of Treg, Th17, Th9 cells and expression of transforming growth factor-β (TGF-β), interleukin-17 (IL-17) and interleukin-9 (IL-9) in peripheral blood of patients with immune thrombocytopenia (ITP) and to explore its role in the pathogenesis of ITP. Fifty-four patients with ITP (ITP group) and 40 healthy volunteers (control group) were selected in our hospital. The of Treg, Th17 and Th9 cells in peripheral blood of 2 groups were measured by flow cytometry, and the expression of cytokines, such as TGF-β, IL-17 and IL-9 in the peripheral blood of 2 groups were detected by enzyme linked immunosorbent assay (ELISA). The level of Treg cells in the peripheral blood of the ITP group was significantly decreased in comparison with the control group, while the levels of Th17 and Th9 cells significantly increased in comparison with the control group (all P<0.01). The expression of cytokine such as TGF-β in the peripheral blood of the case group significantly decreased in comparison with the control group, while the expression levels of IL-17 and IL-9 significantly increased in comparison with the control group (P<0.01). The results of Pearson correlation analysis showed that there was a positive correlation between the level of Treg cells and platelet count (PLT) in peripheral blood of the ITP group (r=0.35, P<0.05), and there were negative correlation between the level rate of Th17, Th9 cells and Plt count (r=-0.37, -0.43, P<0.05); there was a positive correlation between the expression of the TGF-β in the ITP group and Plt count (r=0.46, P<0.05), while the expression of IL-17 and IL-9 showed negative correlation with PLT (r=-0.48, -0.54, P<0.05). The percentage of Treg, Th17 and Th9 cells in the peripheral blood of patients with ITP is abnormal, and the expression of TGF-β, IL-17 and IL-9 also is abnormal, which may play an important role in the pathogenesis of ITP.

Study of Clinical Profile and Immunological Dysfunction in One Hundred Patients of Recurrent Dermatophytosis

Background: An alarming increase in number of patients with chronic and recurrent dermatophytosis has invoked the need to study immunological parameters of the host in addition to traditional pathogens studies. This study was done to evaluate delayed type of hypersensitivity (DTH) response by estimating TH1 cells along with TH17 cells and immediate hypersensitivity (IH) response by estimating TH2 cells population in peripheral blood along with intradermal trichophytin skin test in patients with recurrent dermatophytosis. Methods: In this case-control study, 100 patients with recurrent dermatophytosis and 50 controls were included. Flow-cytometric evaluation of TH1, TH17 and TH2 cells in peripheral blood along with intradermal trichophytin extract test was done. Dermatophytes pathogens were isolated on culture and antifungal drug susceptibility test was done. Relevant risk factors for recurrent disease were analysed and serum IgE levels were estimated. Findings: TH1 cells were reduced in 72.6 % cases vs 52 % controls (p=0.01) and TH17 cells were reduced in 49.4% cases vs 26 % controls (p=0.006). Intradermal trichophytin test demonstrated negative DTH response in 100 % of cases (p=0.0001). Positive IH response was observed in 91% cases vs 68% controls (p=0.0001). T.mentagrophytes complex (95.8%) was the most common species isolated followed by T.rubrum (4.16%). The risk factors associated were family history of tinea, sharing of towels and clothes and corticosteroids use in recent past (p= 0.007, p=0.009, p=0.0001). Serum IgE was elevated in 83.15 % cases (p=0.01). Interpretations:Our study demonstrated impaired DTH response and reduced TH1 and TH17 cell population in patients with recurrent dermatophytosis. Funding Statement: The authors declare: None . Declaration of Interests: The authors declare: None. Ethics Approval Statement: The study protocol was approved by the Institutional Ethics Committee (Intramural) of the Postgraduate Institute of Medical Education and Research, Chandigarh.

Th17 cell frequency is associated with low bone mass in primary sclerosing cholangitis

Osteoporotic fractures are a major cause of morbidity and reduced quality of life in patients with primary sclerosing cholangitis (PSC), a progressive bile duct disease of unknown origin. Although it is generally assumed that this pathology is a consequence of impaired calcium homeostasis and malabsorption, the cellular and molecular causes of PSC-associated osteoporosis are unknown. We determined bone mineral density by dual-X-ray absorptiometry and assessed bone microstructure by high-resolution peripheral quantitative computed tomography in patients with PSC. Laboratory markers of liver and bone metabolism were measured, and liver stiffness was assessed by FibroScan. We determined the frequency of Th17 cells by the ex vivo stimulation of peripheral blood mononuclear cells in a subgroup of 40 patients with PSC. To investigate the potential involvement of IL-17 in PSC-associated bone loss, we analyzed the skeletal phenotype of mice lacking Abcb4 and/or Il-17. Unlike in patients with primary biliary cholangitis, bone loss in patients with PSC was not associated with disease duration or liver fibrosis. However, we observed a significant negative correlation between the bone resorption biomarker deoxypyridinoline and bone mineral density in the PSC cohort, indicating increased bone resorption. Importantly, the frequency of Th17 cells in peripheral blood was positively correlated with the urinary deoxypyridinoline level and negatively correlated with bone mass. We observed that Abcb4-deficient mice displayed a low-bone-mass phenotype, which was corrected by an additional Il-17 deficiency or anti-IL-17 treatment, whereas the liver pathology was unaffected. Our findings demonstrate that an increased frequency of Th17 cells is associated with bone resorption in PSC. Whether antibody-based IL-17 blockade is beneficial against bone loss in patients with PSC should be addressed in future studies. Primary sclerosing cholangitis (PSC) is a cholestatic liver disease characterized by progressive bile duct destruction. One serious complication of PSC is reduced bone mass resulting in increased fracture risk. Herein, we demonstrate that Th17 cells mediate bone loss in PSC by inducing bone resorption, which suggests that antibody-based IL-17 blockade might be beneficial for the treatment of bone loss in affected patients.

Pregnancy Epigenetic Signature in T Helper 17 and T Regulatory Cells in Multiple Sclerosis.

Increasing evidence supports the anti-inflammatory role of estrogens in Multiple Sclerosis (MS), originating from the observation of reduction in relapse rates among women with MS during pregnancy, but the molecular mechanisms are still not completely understood. Using an integrative data analysis, we identified T helper (Th) 17 and T regulatory (Treg) cell-type-specific regulatory regions (CSR) regulated by estrogen receptor alpha (ERα). These CSRs were validated in polarized Th17 from healthy donors (HD) and in peripheral blood mononuclear cells, Th17 and Treg cells from relapsing remitting (RR) MS patients and HD during pregnancy. 17β-estradiol induces active histone marks enrichment at Forkhead Box P3 (FOXP3)-CSRs and repressive histone marks enrichment at RAR related orphan receptor C (RORC)-CSRs in polarized Th17 cells. A disease-associated epigenetic profile was found in RRMS patients during pregnancy, suggesting a FOXP3 positive regulation and a RORC negative regulation in the third trimester of pregnancy. Altogether, these data indicate that estrogens act as immunomodulatory factors on the epigenomes of CD4+ T cells in RRMS; the identified CSRs may represent potential biomarkers for monitoring disease progression or new potential therapeutic targets.

Effects of thermal ablation on Treg/Th17 in hepatocellular carcinoma of mice

The study was aimed to explore the possible function of thermal ablation treatment on T helper 17 (Th17) cells and regulatory T (Treg) cells in transplantation of hepatocellular carcinoma in mice. In total, 60 male C57BL/6 mice were divided into control group, model group, and treat group. Flow cytometry was used to detect the frequency of Th17 and Treg cells in peripheral blood. The levels of interleukin (IL)-17, IL-23, IL-10, and transforming growth factor beta (TGF-β) in serum were detected by enzyme-linked immunosorbent assay (ELISA).The levels of IL-17, RORγt, Foxp3, and TGF-β mRNA in tumor tissues were detected by real-time fluorescence quantitative PCR (qRT-PCR). Compared with the model group, tumor size was significantly decreased after thermal ablation treatment. After treatment, the frequency of Th17 cells in peripheral blood was significantly decreased, while the frequency of Treg cells was profoundly increased ( P &lt; 0.05). The levels of IL-17 and IL-23 were significantly downregulated, while IL-10 and TGF-β levels were upregulated ( P &lt; 0.05). IL-17 and RORγt mRNA levels in tumor tissues were significantly decreased ( P &lt; 0.05), and Foxp3 and TGF-β mRNA levels were significantly increased ( P &lt; 0.05). Thermal ablation treatment plays a positive role in the treatment of hepatoma in mice through affecting the imbalance of Th17/Treg cells.

T helper 17 cells and interleukin-17 in patients with rheumatoid arthritis

Rheumatoid Arthritis (RA) is one of the most prevalent autoimmune disease which may lead to a shorter life expectancy and lessened personal satisfaction. it is driven by effector T cells, particularly Th17 cells which possess a proinflammatory activity via the production of potent proinflammatory molecules IL-17. We aimed to assess and find possible correlations between the 28-joint Disease Activities Scores (DAS28), Th17 cells frequencies and IL-17 serum levels, and evaluation of the effect of anti-rheumatic therapy on Th17 cells and IL-17 levels. The frequencies of the circulating Th17 cells and serum levels of IL-17 were quantified using flow cytometry analysis and ELISA, respectively, in RA patients both before (baseline) and four months after anti-rheumatic therapy. Th17 cells in Peripheral Blood (PB) and serum IL-17 were found to be significantly increased in RA patients than in controls. The frequencies of circulating Th17 cells, the serum level of IL-17, and DAS28 score showed significant decline after therapy, the circulating Th17 cells, the serum levels of IL-17 were positively correlated with DAS28, also Th17 cells significantly correlated with serum IL-17. This study demonstrated increased level of Th-17 cells and serum IL-17 in RA indicating a role in pathogenesis and disease activity.

Comparison of Peripheral Blood Th17 Cells and Associated Cytokines in Fingolimod-Receiving and Untreated Multiple Sclerosis Patients

Comparison of Peripheral Blood Th17 Cells and Associated Cytokines in Fingolimod-Receiving and Untreated Multiple Sclerosis Patients

Importance of Th22 Cell Disequilibrium in Immune Thrombocytopenic Purpura.

BackgroundThe disequilibrium of T helper (Th) cells play an important role in the occurrence and development of immune thrombocytopenic purpura (ITP). Th22 cells, as a newly discovered subset of T lymphocytes, plays an important role in autoimmune disorders and inflammatory diseases.Material/MethodsThis study explored the role of different lymphocyte subsets in chronic ITP. To explore the value of Th22 cells in the diagnosis of ITP, the numbers of Th1, Th17, and Th22 cells were detected by a 4-color flow cytometric in 32 chronic ITP patients and 30 healthy controls.ResultsOur data showed that, compared with healthy controls, the numbers of circulating Th1, Th17, and Th22 (p<0.05) cells increased significantly in ITP patients, and Th22 cells were correlated positively with Th1 cells (r=0.4041, p<0.01) and Th17 cells (r=0.4637, p<0.05). Moreover, a positive relationship was found between Th1/Th22 cells and Th1 cells (r=0.7696, p<0.001).ConclusionsA disequilibrium expression profile of Th22 cells in peripheral blood was associated with pathogenesis of ITP, possibly through cooperatively working with Th17 and Th1, which may provide a novel approach for diagnosis of ITP.

Aberrant Expression of MicroRNAs in CD4+ Cells May Contribute to the Imbalance of Th17/Treg Cells in Primary Immune Thrombocytopenia

Backgrounds:Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by reduced platelet count and an increased risk of bleeding. The imbalance of Treg/Th17 cells has been demonstrated in ITP, but the mechanism of Th17/Treg cells imbalance is still not clear. In this study, we aimed to investigate whether the expression of helper T (Th) or Treg cell-related microRNAs, such as miR-183-96-182 cluster, miR-17-5p, miR-99a, miR-146-5p, miR-155-5p, miR-181-5p, and miR-326, regulates the ratio of Th17/Treg in CD4+ T cells and could be used to evaluate the clinical implications of ITP patients.Methods: Peripheral blood was obtained from 54 patients with active ITP and 34 healthy controls. Peripheral blood mononuclear cells (PBMCs) were isolated using Ficoll density-gradient centrifugation and the CD4+ cells were separated by immuno-magnetic microbeads selection. Amplification technique of RT-PCR using stem-loop primers was applied to detect the relative expression of microRNAs (miR-17-5p, miR-99a, miR-96-5p, miR-146a-5p, miR-155-5p, miR-181a-5p, miR-182-5p, miR-183-5, miR-326) and U6 was normalized as control for miRNA quantification. The frequencies of Th17 and Treg cells in peripheral blood were analyzed by flow cytometry. The mRNA expression levels of Il-6, Il-10, Il-17, Rorγ-t and Foxp-3 in CD4+ cells were determined by RT-PCR. Platelet autoantibodies specific for GPIIb/IIIaor GPIb/IX were measured using MAIPA method. CD4+ cells were transfected with miRNAs (miR-99a, miR-182-5p, miR-183-5), mimics or inhibitors, which were used to detect the function of miRNAs. Cytokines in culture medium were determined by ELISA.Results: Our results showed that the relative expression of miR-182-5p and miR-183-5p in CD4+ cells was significantly increased in active ITP patients, compared to healthy controls (miR-182-5p, median 9.2678 vs 5.2723, p < 0.05, Fig. 1a; miR-183-5p, median 5.4435 vs 2.009, p < 0.05, Fig. 1b). In addition, the relative expression of miR-99a in ITP patients was lower than that of healthy controls (median 3.4214 vs 7.9648, p < 0.05; Fig. 1c). Moreover, the frequency of Treg cells decreased significantly in ITP patients compared to those in controls (1.89±1.59% vs 4.12±1.42%, p < 0.05; Fig. 2a), and the percentage of Treg cells was positively correlated with the relative expression of miR-99a in ITP patients(r=0.461, p< 0.05; Fig. 2c) and health controls(r=0.729, p< 0.05; Fig. 2d). Though the percentage of Th17 cells increased in ITP patients compared to the health controls (3.51±2.13%vs 1.85±0.63%, p < 0.05; Fig. 2b), there was no correlation between the percentage of Th17 and the relative expression of microRNAs in ITP patients or health controls. Besides, there was no correlation between the expression of mRNAs (Il-10, Il-17, Rorγ-t and Foxp-3) and microRNAs (miR-99a, miRNA-182-5p or miR-183-5p). No significant correlation was found between the microRNAs expression and platelets counts or different autoantibody subsets in ITP patients. The relative expression of other microRNAs (miR-17-5p, miR-96-5p, miR-146a-5p, miR-155-5p, miR-181-5p, miR-326) revealed no difference in CD4+ cells between ITP patients and health controls. Furthermore, the down-regulated expression of miR-183-5p with inhibitors promoted to the differentiation of Th17 cells(Fig. 3a), while up-regulated expression of miR-99a with mimics contributed to Treg cells in CD4+ cells from ITP patients (Fig. 3b). Meanwhile, the IL-17A in culture medium decreased in inhibitor group of miR-183-5p or miR-183-5p. However, miR-182-5p inhibitor had no effect on the differentiation of Th17 cells.Conclusions: Our results show the abnormal expression of microRNAs (miR-99a, miRNA-182-5p and miR-183-5p) in CD4+ cells and the miR-99a was closely correlated with the Treg cells. The aberrant expression of microRNAs may contribute to the imbalance of Th17/Treg cells in the development of ITP patients and potentially constitute a novel therapeutic target. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Effects of Early Enteral Nutrition on Immune Function and Prognosis of Patients With Sepsis on Mechanical Ventilation.

To explore the therapeutic effects of early enteral nutrition (EEN) on patients with sepsis on mechanical ventilation. Patients with sepsis on mechanical ventilation in the medical intensive care unit (ICU) from January 2013 to March 2016 were treated with enteral nutrition. Patients treated within 48 hours of initiation of mechanical ventilation were assigned to the EEN group, and the rest were assigned to the delayed enteral nutrition (DEN) group. Peripheral blood Th17 cells and Treg cells, endotoxin (ET) level, 28-day mortality, duration of mechanical ventilation, lengths of ICU stay and hospital stay, and incidence of ICU-acquired weakness (ICU-AW) were analyzed between the 2 groups. The proportion of Th17 cells and ET levels in the EEN group were significantly lower than those in the DEN group, whereas the proportion of Treg cells in the EEN group was remarkably higher than that in the DEN group (P < .05). The duration of mechanical ventilation, lengths of ICU stay and hospital stay, and incidence of ICU-AW were higher in the DEN group than in the EEN group (P < .05), but there was no significant difference in the 28-day mortality between the 2 groups. Patients with sepsis mainly present with an increased proportion of Th17 cells in the early stage, manifesting as enhanced immune response. Early enteral nutrition can inhibit the excessive immune response, shorten the duration of mechanical ventilation, lengths of ICU stay and hospital stay, and reduce the incidence of ICU-AW, but it has no obvious effect on 28-day mortality.

IL-17A contributes to HSV1 infection-induced acute lung injury in a mouse model of pulmonary fibrosis.

BackgroundPatients with idiopathic pulmonary fibrosis (IPF) often experience acute exacerbation (AE) after an episode of common cold.AimsTo establish a mouse model of virus infection‐induced AE‐IPF and investigate the mechanism underlying the AE‐IPF.MethodsHerpes simplex virus 1 (HSV1) was inoculated intranasally to wild‐type (WT) and IL‐17A gene knockout (IL‐17A‐/‐) mice 21 days after intratracheal administration of bleomycin (BLM).Results HSV1 infection caused acute exacerbation in mice with BLM‐induced fibrosis. Compared with the BLM+Saline mice, the mice with BLM+HSV1 showed significantly higher acute lung injury (ALI) score (P < 0.0001), lower survival rate (100% vs 21.4%, P < 0.0001), poorer lung function and higher inflammatory response representing by increased total inflammatory cells in bronchoalveolar lavage fluid (BALF) (P = 0.0323), increased proportion of Th17 cells in peripheral blood (P = 0.0004) and higher inflammatory factors in BALF. In addition, HSV1 infection increased the expression of endoplasmic reticulum stress (ERS)‐related proteins in mice with BLM‐induced fibrosis. The inhibition of ERS by tauroursodeoxycholic acid (TUDCA, an ERS inhibitor) significantly reduced the IL‐17A levels in BALF (P = 0.0140) and TH17 cells in the peripheral blood (P = 0.0084) of mice with BLM+HSV1, suggesting that suppression of ERS may reduce TH17 response in mice with AE‐IPF. Compared with WT mice with BLM+HSV1, IL‐17A‐/‐ mice with BLM+HSV1 had lower ALI score (P = 0.0119), higher survival rate (78.6% vs 21.4%, P = 0.004), improved lung function, and milder inflammatory response.Conclusions HSV1 infection in addition to BLM‐induced IPF can successfully establish AE‐IPF in mice. IL‐17A and ERS promote lung inflammation in AE‐IPF development.

Peripheral Th17 cells expressing β7 intestinal homing receptor in recent and chronic HIV infections.

The objective of this study was to conduct an analysis of peripheral blood Th17 cells with the ability to home to gut mucosa (CD4+ Th17+ β7+ ) during recent or chronic human immunodeficiency virus (HIV) infections. The relationship between HIV load and systemic inflammation markers was studied. Twenty-five patients with recent (n=10) or chronic (n=15) untreated HIV infections; 30 treated HIV-infected patients with undetectable HIV load at the time of inclusion and 30 healthy controls were included. Bacterial translocation markers (16S rDNA), soluble CD14 (sCD14) and interleukin (IL)-6 monocyte activation parameters, CD4/CD8 ratio and T helper type 17 (Th17) subpopulations [CD4+ Th17+ expressing the IL-23 receptor (IL-23R) or β7] were analysed at baseline and after 6 and 12months of anti-retroviral therapy (ART). 16S rDNA was detected in all patients. Significantly increased serum levels of sCD14 and IL-6 and a decreased CD4/CD8 ratio were observed in patients. Similar percentages of CD4+ IL-23R+ and CD4+ Th17+ β7+ cells were observed in healthy controls and patients at baseline. After 12months of therapy, patients with a recent HIV infection showed significant increases of CD4+ IL-23R+ and CD4+ Th17+ β7+ cell percentages and a decrease in IL-6 levels, although 16S rDNA continued to be detectable in all patients. No significant differences were observed in Th17 subpopulations in patients with chronic HIV infection after therapy. Early initiation of ART helps to increase the number of Th17 cells with the ability to home to the intestinal mucosa and to partially restore gut mucosal homeostasis. These results provide a rationale for initiating ART during the acute phase of HIV infection.

Interleukin-17 inhibits the growth of oral squamous cell carcinoma by promoting the differentiation of T helper 17 cells

Background: The infiltration of T helper 17 (Th17) cells has been reported in multiple solid tumors. Recent studies implicated that Th17 cells played an inhibitory role in the tumor growth. However, if Th17 cells infiltrated and played a role in oral squamous cell carcinoma (OSCC) remained unknown. Methods: Fluorescence activated cell sorting (FACS) was performed to confirm the increase of Th17 cells in the peripheral blood and the infiltration in tumor samples from OSCC patients. To mimicking the effect of Th17 cells on OSCC growth, an OSCC line stably expressing human interleukin-17A (IL-17A) was established. Human-PBL-SCID-beige mice were employed as the hosts for the implantation of OSCC/IL-17A cells. Quantitative PCR, ELISA and Western blotting were performed to analyze Th17 differentiation and function in the implanted tumors. Results: The percentage of Th17 cells increased significantly in both the peripheral blood and the tumor tissues from OSCC patients. Expression of IL-17A promoted the differentiation of Th17 cells and suppressed the growth of implanted OSCC tumors. The transcription as well as the protein levels of IL-6 and granzyme B in the implanted OSCC cells was remarkably elevated by IL-17A expression. Conclusions: The increased infiltration of Th17 cells was suggested to result in a therapeutic effect on OSCC as Th17 cells did in other tumors. IL-17 could promote the differentiation of Th17 cells by increasing IL-6 expression. The inhibitory effect of Th17 cells on OSCC growth was associated with their increased cytotoxic activity.

Detection of Treg/Th17 cells and related cytokines in peripheral blood of chronic hepatitis B patients combined with thrombocytopenia and the clinical significance

Changes of regulatory T (Treg) cells and Th17 cells, and related cytokines in peripheral blood of patients with chronic hepatitis B combined with thrombocytopenia were investigated to explore the relationship with treatment outcomes. A total of 45 chronic hepatitis B patients combined with thrombocytopenia were selected in Heilongjiang Provincial Hospital from June 2015 to December 2016. All patients were treated with prednisolone acetate + γ globulins for 60 days. Treg cells and Th17 cells in peripheral blood were detected by flow cytometry, and IL-10, TGF-β, IL-17, IL-21 and IL-22 in peripheral blood were detected by ELISA before and after treatment. No significant differences in the percentages of Treg and Th17, and levels of IL-10, TGF-β, IL-17, IL-21 and IL-22 were found in non-responders (n=17, platelets <100×109/l) before and after treatment (P>0.05). After treatment, percentage of Treg was significantly increased (higher than that of non-responders) and percentage of Th17 was significantly decreased (lower than that of non-responders) in responders (P<0.05). In addition, serum levels of IL-10 and TGF-β were significantly increased (higher than that of non-responders) and serum levels of IL-17, IL-21 and IL-22 were significantly decreased (lower than that of non-responders) in responders (P<0.05). The results showed that after treatment, the number of Treg cells was increased, the number of Th17 cells was decreased, the levels of anti-inflammatory factors IL-10 and TGF-β were increased, and levels of pro-inflammatory factors IL-17, IL-21 and IL-22 were decreased in chronic hepatitis B patients combined with thrombocytopenia, indicating the decreased autoimmune response and improved thrombocytopenia. The changes were closely related to the complete response.

Higher levels of serum interleukin-35 are associated with the severity of pulmonary fibrosis and Th2 responses in patients with systemic sclerosis.

The aim of the study is to investigate the levels of serum interleukin-35 (IL-35) before and after treatment and its relationship with clinical parameters as well as the frequency of different subsets of CD4+ T cells in patients with systemic sclerosis (SSc) to explore the role of IL-35 in the pathogenesis of SSc. The levels of serum IL-35, interferon-γ (IFN-γ), IL-4, IL-17A, and IL-10 in 49 patients with SSc and 50 age- and gender-matched healthy subjects were measured by enzyme-linked immunosorbent assay (ELISA). The percentages of peripheral blood Th1, Th2, Th17 cells and Tregs in 49 SSc patients and 20 healthy controls were characterized by flow cytometry. The relationship between the levels of serum IL-35 and the percentages of different subsets of CD4+ T cells, disease duration, the values of forced vital capacity (FVC), modified Rodnan skin scores (MRSS) or high-resolution computed tomography (HRCT) scores was analyzed in patients with SSc. The levels of serum IL-35 in SSc patients were significantly higher than that of healthy controls (P < 0.001), but significantly reduced after treatment for 3months (P = 0.001). The levels of serum IL-35 were positively correlated with the HRCT scores in SSc patients (P = 0.014) and with disease duration in patients with diffuse cutaneous SSc (P = 0.03), but negatively correlated with the FVC values in SSc patients (P = 0.034). In comparison with that in the healthy controls, significantly decreased percentages of Th1, but increased Th2 and Th17 cells were detected in patients, leading to reduced ratios of Th1/Th2 and increased ratios of Th17/Tregs (P < 0.001). The levels of serum IL-35 were positively correlated with IL-4 (P = 0.036) and tended to be positively associated with the frequency of Tregs in SSc patients (P = 0.054). Higher levels of serum IL-35 may be associated with the development of SSc and severity of pulmonary fibrosis in SSc patients.