Dexamethasone Reduces IL-17 and Tim-3 Expression in BALF of Asthmatic Mice

Summary： This study investigated the expression of interleukin-17 （IL-17） and T cell immunoglobulin mucin and domain-containing molecule-3 （Tim-3） in bronchoalveolar lavage fluid （BALF） of asthmatic mice and the effect of dexamethasone （DEX） on these factors. Thirty-six mice were randomly divided into three groups： normal group, asthmatic group and DEX group. The mouse model of asthma was es- tablished by sensitization with ovalbumin in both the asthmatic and DEX groups. The levels of IL-6, IL-10, IL-17 and TGF-β were measured in BALF by enzyme-linked immunesorbent assay （ELISA）. The mRNA expression level of Tim-3 was detected by reverse transcription polymerase chain reaction （RT-PCR）. The ratio of Tim-3＋CD4＋ cells to total CD4＋ cells in BALF was determined by flow cy- tometry. Differential inflammatory cells in BALF were detected. The correlations among IL-17, IL-6, IL-10, Tim-3 and inflammatory cells were analyzed. The results showed that the levels of IL-17, IL-6 and Tim-3 were substantially increased and the IL-10 level decreased in BALF in the asthmatic mice, which was significantly reversed by DEX treatment. IL-17 expression was positively correlated with IL-6 and Tim-3 expression and the number of inflammatory cells but negatively with IL-10 expression. These results indicate that the increased expression of IL-17 and Tim-3 in BALF may be implicated in the occurrence and development of asthmatic inflammation; the mechanism by which DEX suppresses asthmatic airway inflammation involves down-regulation of IL-17 and Tim-3 levels.

Th17/Treg Imbalance in Malignant Pleural Effusion

Both T helper IL-17-producing cells （Thl7 cells） and regulatory T cells （Tregs） have been found to be increased in malignant pleural effusion （MPE）. However, the possible imbalance between Thl7 cells and Tregs, as well as the association of.Thl7/Treg and Thl/Th2 cells in MPE remains to be elucidated. The objective of the present study was to investigate the distribution of Th 17 cells in relation to Tregs, as well as Thl/Th2 balance in MPE. The number ofThl7, Tregs, Thl, and Th2 cells in MPE and peripheral blood was determined by using flow cytometry. The relationship among the number of Thl7, Tregs, Thl, and Th2 cells was explored. It was found that the number of Thl7, Tregs, Thl, and Th2 cells was all increased in MPE as compared with the corresponding peripheral blood. The number of Thl7 cells was correlated negatively with Tregs in MPE, but not in blood. Thl7 cells and Thl7/Treg ratio were positively, and Tregs were negatively, correlated with Thl cells, but not with either Th2 cells or Th1/Th2 ratio in MPE. This study supports earlier data that both Thl7 cells and Treg are present at higher frequencies in MPE than in the autologous blood. For the first time, we show that Thl7/Treg imbalance exists in MPE.

Correlation of Thl7 cells and CD4＋CD25＋ regulatory T cells with clinical parameters in patients with systemic sclerosis

Background Systemic sclerosis （SSc） is an autoimmune disease that has three major components： inflammation, fibrosis, and vasculopathy. T-helper 17 cell （Th17） and regulatory T cell （Treg） are considered to be critical for autoimmune disease pathogenesis. The role of Th17 and Treg in SSc is still unclear. The aim of this study was to detect the presence of Th17s and CD4＊CD25~ Tregs in peripheral blood samples from SSc patients and to investigate the possible roles of these two T cell subsets in SSc pathogenesis. Methods Th17s （CD4 and IL-17 positive） and CD4＊CD25~ Tregs （CD4, CD25 and Foxp3 positive） in the peripheral blood mononuclear cells of 53 SSc patients and 27 healthy controls were counted by flow cytometry. The differences between SSc and control patients were analyzed. Clinical parameters, including disease duration, duration of the second symptoms, Modified Rodnan Skin Score （MRSS）, anti-topoisomerase I antibody, anti-U1 ribonucleoprotein （RNP） antibody, systemic involvements, pulmonary function test （PFT） and high resolution computed tomography （HRCT） score were prospectively collected following EUSTAR （EULAR scleroderma trial and research group） protocols. The correlations between the experimental and clinical data were investigated. Results The ratio of Th17 in SSc patients was significantly elevated compared to healthy controls （8.74% vs. 4.41%, P 〈0.001）. The amount of Th17 was positively correlated with disease duration （R=-0.531, P=-0.013） and duration of the second symptoms （R=-0.505, P=0.023）. The ratio of CD4＊CD25＊ Treg in SSc patients also significantly differed from the healthy controls （3.04% vs. 2.24%, P=0.018）. Elevated Tregs were more frequently observed in patients with a high interstitial lung disease （ILD） score on computed tomography （24/36） compared with patients with normal ILD scores （4/12, ,P=-0.043）. Elevated Tregs were also more often observed in patients with low carbon monoxide diffusing capacity （DLCO） （24/34） compared with patients with normal DLCO （4/11, P=0.042）. Conclusions T cell abnormalities are remarkable in systemic sclerosis. Th17s proliferate and their numbers increase with lengthened disease duration. Th17s might participate in both inflammation and fibrosis by secreting IL-17. CD4＋CD25＋ Tress also proliferate in SSc and may play important roles in promoting fibrosis.

Coexistence of Th1/Th2 and Thl7/Treg imbalances in patients with allergic asthma

Background Recent recognition is that Th2 response is insufficient to fully explain the aetiology of asthma. Other CD4^＋ T cells subsets might play a role in asthma. We investigated the relative abundance and activities of Thl, Th2, Th17 and CD4^＋CD25^＋ Treg cells in patients with allergic asthma. Methods Twenty-two patients with mild asthma, 17 patients with moderate to severe asthma and 20 healthy donors were enrolled. All patients were allergic to house dust mites. Plasma total IgE, pulmonary function and Asthma Control Questionnaire were assessed. The proportions of peripheral blood Thl, Th2, Th17 and CD4^＋CD25^＋ Treg cells were determined by flow cytometry. The expression of cytokines in plasma and Jn the culture supernatant of peripheral blood mononuclear cells was determined by enzyme linked, immunosorbent assay. Results The frequency of blood Th2 cells and IL-4 levels in plasma and culture supernatant of peripheral blood mononuclear cells were increased in all patients with allergic asthma. The frequency of Th17 cells and the plasma and culture supernatant levels of IL-17 were increased, whereas the frequency of CD4^＋CD25^＋ Treg cells and plasma IL-10 levels were decreased in patients with moderate to severe asthma. Dermatophagoides pteronyssinus specific IgE levels were positively correlated with the percentage of blood Th2 cells and plasma IL-4 levels. Forced expiratory volume in the first second was negatively correlated with the frequency of Th17 cells and plasma IL-17 levels, and positively correlated with the frequency of Treg cells. However, mean Asthma Control Questionnaire scores were positively correlated with the frequency of Th17 cells and plasma IL-17 levels, and negatively correlated with the frequency of Treg cells. Conclusions Imbalances in Thl/Th2 and Th17/Treg were found in patients with allergic asthma. Furthermore, elevated Th17 cell responses, the absence of Tregs and an imbalance in Th17/Treg levels were associated with moderate to severe asthma.

Th17 Cells in autoimmune diseases

Th17 cells are a new subset of CD4^＋ T cells fungi. Accumulating evidence suggests that Tb17 cells involved in the clearance of extracellular pathogens and and their signature cytokines have a pivotal role in the pathogenesis of multiple autoimmune-mediated inflammatory diseases. Here, we summarize recent research progress on Th17 function in the development and pathogenesis of autoimmune diseases. We also propose to identify new small molecule compounds to manipulate Th17 function for potential therapeutic application to treat human autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, Sjogren＇s syndrome, inflammatory bowel disease, and multiple sclerosis.

Ma Huang Tang ameliorates asthma though modulation of Th1/Th2 cytokines and inhibition of Th17 cells in ovalbumin-sensitized mice

AIM： Ma Huang Tang （Ephedra decoction, MHT） is a famous classical formula from Shang Han Lun by Zhang Zhongjing in the Han Dynasty. The anti-asthmatic effects of MHT and the possible mechanisms were tested. METHOD： An asthma model was established by ovalbumin （OVA）-induction in mice. A total of forty-eight mice were randomly assigned to six experimental groups： control, model, dexamethasone （2 mg·kg^-1） and MHT （5, 10, and 20 mg·kg^-1）. Airway resistance （Raw） was measured by the forced oscillation technique, histological studies were evaluated by hematoxylin and eosin （HE） staining, Thl/Th2 and Th17 cytokines were evaluated by enzyme-linked immunosorbent assay （ELISA）, and Thl7 cells were evaluated by flow cytometry （FCM）.RESULTS： This study demonstrated that MHT inhibited OVA-induced increases in Raw and eosinophil cotmt; interleukin （IL）-4 and IL-17 levels were recovered in bronchoalveolar lavage fluid, increased IFN-γ level in bronchoalveolar lavage fluid. Histological studies demonstrated that MHT substantially inhibited OVA-induced eosinophilia in lung tissue. Flow cytometry studies demonstrated that MHT substantially inhibited Thl 7 cells.CONCLUSION： These findings suggest that MHT may effectively ameliorate the progression of asthma, and could be further investigated for potential use as a therapy for patients with allergic asthma,