Bile Acids and Salts ; Gastrointestinal Microbiome ; Hepatitis B virus ; Humans ; Liver/pathology* ; Liver Cirrhosis/pathology* ; Th17 Cells

Aplastic anemia (AA) is an autoimmune disease characterized by destruction of hematopoietic tissue resulting in hyperfunction of effector T-lymphocytes. Recent studies indicate that Th17 and Treg cells are functionally antagonistic each other, and the increase of Th17 cells and decrease of Treg cells are closely related with AA. In vivo experiments showed that both anti-IL-17 treatment and Treg cell infusion can protect against immune-mediated bone marrow failure in mouse with AA. This review summarizes the recent progress of study on imbalance of Th17/Treg cells in AA, so as to explore the pathogenesis of AA and provide approach to clinical treatment. The main problems that are discussed in this review include biological characteristics of Th17/Treg cells, the regulation of Th17/Treg cell balance and related cytokines, the relationship between Th17/Treg cells and AA.
Anemia, Aplastic ; immunology ; pathology ; Humans ; T-Lymphocytes, Regulatory ; immunology ; Th17 Cells ; immunology

Both T helper IL-17-producing cells (Th17 cells) and regulatory T cells (Tregs) have been found to be increased in malignant pleural effusion (MPE). However, the possible imbalance between Th17 cells and Tregs, as well as the association of Th17/Treg and Th1/Th2 cells in MPE remains to be elucidated. The objective of the present study was to investigate the distribution of Th17 cells in relation to Tregs, as well as Th1/Th2 balance in MPE. The number of Th17, Tregs, Th1, and Th2 cells in MPE and peripheral blood was determined by using flow cytometry. The relationship among the number of Th17, Tregs, Th1, and Th2 cells was explored. It was found that the number of Th17, Tregs, Th1, and Th2 cells was all increased in MPE as compared with the corresponding peripheral blood. The number of Th17 cells was correlated negatively with Tregs in MPE, but not in blood. Th17 cells and Th17/Treg ratio were positively, and Tregs were negatively, correlated with Th1 cells, but not with either Th2 cells or Th1/Th2 ratio in MPE. This study supports earlier data that both Th17 cells and Treg are present at higher frequencies in MPE than in the autologous blood. For the first time, we show that Th17/Treg imbalance exists in MPE.
Adult ; Female ; Humans ; Male ; Middle Aged ; Pleural Effusion, Malignant ; immunology ; pathology ; T-Lymphocytes, Regulatory ; immunology ; pathology ; Th17 Cells ; immunology ; pathology

Animals ; CD4-Positive T-Lymphocytes ; immunology ; Humans ; Periodontal Diseases ; immunology ; pathology ; T-Lymphocytes, Regulatory ; immunology ; Th1 Cells ; immunology ; Th17 Cells ; immunology ; Th2 Cells ; immunology

OBJECTIVEto observe the alteration of T helper cells 17(Th17) in mice with acute viral myocarditis (VMC) induced by coxsackie virus B3 (CVB3), explore the role of Th17 in mice VMC.

METHODSCVB3 or PBS was peritoneally injected to Balb/c male mice. Pathological scores were determined in hematoxylin-eosin stained sections and flow cytometric analysis was used to evaluate the frequencies of Th17 subsets in CD4(+) T cells on 7, 14, 21, 28 and 42 days after virus injection.

RESULTSthere were significant difference of the pathological scores between the VMC mice and the control ones (P < 0.05). The pathological scores of 7 d VMC subgroup were higher (1.8 ± 0.5) than those of 0 d VMC subgroup, and the scores of 14 d subgroup were highest (2.8 ± 0.4) among the six subgroup of VMC mice, and then showed a decline tendency from 21 d group. Statistical difference of the proportion of Th17 cells were seen between the VMC and controls on different time points (P < 0.05). When compared with the 0 d VMC subgroup the proportion of spleen Th17 cells increased in 7 d VMC subgroup [(2.23 ± 0.89)%], and peaked on 28 d [(5.00 ± 0.81)%]. The results of Th17 proportion were lower than those of the 28 d subgroup.

CONCLUSIONSour data show that differentiated Th17 cells might be involved in the inflammation process of CVB3 induced VMC in mice.

Animals ; Coxsackievirus Infections ; immunology ; pathology ; Enterovirus ; Male ; Mice ; Mice, Inbred BALB C ; Myocarditis ; immunology ; pathology ; virology ; Myocardium ; pathology ; Th17 Cells ; immunology

Oral lichen planus (OLP) is considered a T cell-mediated autoimmune disease with unknown aetiology. T helper cells appear to play an important role in the pathogenesis of OLP. We investigated the possible role of T helper cells, Th1 and Th17, in the lesions and circulation of patients with OLP. Forty patients with OLP and 15 healthy volunteers were recruited. Double immunofluorescence staining was used to detect Th1 and Th17 cells in the OLP lesions, and intracellular cytokine staining and flow cytometry to evaluate the proportion of Th1 and Th17 cells in peripheral blood. The levels of serum interferon (IFN)-γ and interleukin (IL)-17 were assessed by using an enzyme-linked immunosorbent assay. It was found that Th17 cells, as well as Th1 cells, were present in OLP lesions. The proportion of peripheral Th1 and Th17 cells was significantly increased in patients with OLP. The proportion of Th17 cells in atrophic-erosive OLP was elevated as compared with that in reticular OLP. Serum IL-17 levels in OLP patients were significantly higher than in controls, and those in the atrophic-erosive OLP group were increased as compared with the reticular OLP group. However, the levels of serum IFN-γ were slightly decreased in OLP patients. Our data suggested that Th1 and Th17 cells in the local lesions and peripheral blood may be associated with the pathogenesis of OLP, and that IL-17 may be an important proinflammatory cytokine in OLP. These findings enhance our understanding of OLP pathogenesis.
Child ; Female ; Humans ; Interferon-gamma ; immunology ; Interleukin-17 ; immunology ; Lichen Planus, Oral ; immunology ; pathology ; Male ; Middle Aged ; Th1 Cells ; immunology ; Th17 Cells ; immunology

OBJECTIVETo explore the role of Th17 cells in early onset of acute graft-versus-host disease (aGVHD) and its mechanism.

METHODSMice aGVHD model was established by irradiated BABL/c mice inoculated with mixed suspension of C57BL/6 bone marrow cells and splenocytes. The mice were divided into 4 groups: (1) normal control, (2) irradiated group, (3) allo-BMT + DMSO group, (4) allo-BMT + halofuginone (HF) group. HF was given intraperitoneally at 5 µg per mouse from -1 d to +10 d after allogeneic bone marrow transplantation(allo-BMT).Mice aGVHD symptoms and survival were observed. Th1/Th17 cells ratio was evaluated by flow cytometry.

RESULTSAll the experimental groups (3) and (4) developed aGVHD after transplantation. More severe aGVHD was observed in group (4) than in group (3). HF prevented cutaneous aGVHD in all the mice, but augmented hepatic and small intestine GVHD. The percentage of Th17 cells and the ratio of Th1/Th17 were significantly higher while the percentage of Th1 cells was significantly lower in group (4) at day +6 (P < 0.05).

CONCLUSIONEarly blockage of Th17 cell results in increase of Th1 cell percentage, which exacerbates aGVHD.

Animals ; Bone Marrow Transplantation ; Female ; Graft vs Host Disease ; etiology ; pathology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Th1 Cells ; cytology ; Th17 Cells ; cytology ; Transplantation, Homologous

OBJECTIVETo study the dynamic changes in Th17 cells and CD4⁺ CD25⁺ regulatory T cells (Treg) in the spleen and to analyze their relationship with airway remodeling.

METHODSA total of 48 female specific pathogen-free Balb/c mice were randomly divided into control and asthmatic groups. To establish the asthmatic airway remodeling model, the mice were sensitized to ovalbumin (OVA) through intraperitoneal injection of OVA and aluminum hydroxide suspension and challenged by inhalation of aerosol OVA. The matched control group was treated with normal saline instead. In 24 hours after 2-week, 4-week, and 8-week aerosol inhalation, 8 mice were randomly selected from each group and sacrificed. Then histopathological examination of the left lung was performed to measure the degree of airway remodeling. The percentages of Th17 and CD4⁺ CD25⁺ Treg cells in total CD4(+) cells from the spleen were determined by flow cytometry.

RESULTSIn the asthmatic group, the ratios of total bronchial wall area to bronchial basement membrane perimeter (WAt/Pbm) and bronchial smooth muscle area to bronchial basement membrane perimeter (WAm/Pbm) significantly increased as the challenge proceeds (P<0.01). The percentage of Th17 cells derived from the cell suspension of the spleen gradually increased and it was positively correlated with the degree of asthmatic airway remodeling (P<0.01). The percentage of CD4⁺ CD25⁺ Treg cells from the suspension gradually decreased and it was negatively correlated with the degree of asthmatic airway remodeling (P<0.01).

CONCLUSIONSIn mice with asthma, as the challenge proceeds, the airway remodeling becomes more severe, the percentage of Th17 cells increases, and the percentage of CD4⁺ CD25⁺ Treg cells decreases. The immunological imbalance is possibly one of the important factors inducing airway remodeling.

Airway Remodeling ; Animals ; Asthma ; immunology ; pathology ; Disease Models, Animal ; Female ; Lung ; pathology ; Mice ; Mice, Inbred BALB C ; T-Lymphocytes, Regulatory ; immunology ; Th17 Cells ; immunology

OBJECTIVETo investigate the ratio of Th17 cells and CD4⁺CD25⁺Foxp3⁺ regulatory T (Treg) cells in peripheral blood from patients with multiple myeloma (MM) and explore its pathological effects.

METHODS70 MM patients were divided into three groups: newly diagnosed group (n=30), plateau stage group (n=23) and relapsed/refractory group (n=17). The controls consisted of 20 healthy donors. The frequencies of Th17 and Treg cells were detected by flow cytometry.

RESULTSCompared with controls [(0.72±0.33)%] and plateau stage group [(0.74±0.29)%], frequencies of Th17 cells were higher in newly diagnosed group [(1.62±0.65)%] and relapsed/refractory group [(1.45±0.51)%], respectively (P<0.05). Compared with controls [(2.33±0.90)%] and plateau stage group [(1.69±0.70)%], frequencies of Treg cells were significantly lower in newly diagnosed group [(0.55±0.23)%] and relapsed/refractory group [(0.82±0.54)%], respectively (P<0.05). The ratios of Th17/Treg in newly diagnosed group and relapsed/refractory group were higher than those in controls (P<0.05). There were no differences of the frequencies of CD3⁺CD4⁺ T cells and Th17 cells between plateau stage group and controls. The frequencies of Treg cells were significantly lower in plateau stage group than that in controls (P<0.05), and the ratio of Th17/Treg was significantly higher in plateau stage group than that in controls (P<0.05).

CONCLUSIONThe remarkable abnormality of T cells subsets was reduction of CD4⁺ T cells in MM. Higher frequency of Th17 and lower ratio of Treg could lead to imbalance of Th17/Treg, which may play a critical role in the pathogenesis of MM.

Adult ; Aged ; Female ; Flow Cytometry ; Humans ; Lymphocyte Count ; Male ; Middle Aged ; Multiple Myeloma ; immunology ; pathology ; T-Lymphocytes, Regulatory ; cytology ; Th17 Cells ; cytology

OBJECTIVETo study the dynamic changes in the percentage of Th17 cells/CD4CD25regulatory T cells after intervention with montelukast sodium, a leukotriene receptor antagonist, in asthmatic mice and the association between them.

METHODSBalb/c mice were randomly divided into blank group, asthma group, and montelukast sodium group. The asthmatic mouse model of airway remodeling was established by sensitization with intraperitoneal injection of chicken ovalbumin (OVA) and aluminum hydroxide suspension and aerosol inhalation of OVA. The mice in the blank group were given normal saline, and those in the montelukast sodium group were given montelukast sodium by gavage before aerosol inhalation. Eight mice were randomly sacrificed within 24 hours after 2, 4, and 8 weeks of aerosol inhalation. The pathological sections of lung tissue were used to observe the degree of airway remodeling. Flow cytometry was used to measure the percentages of Th17 cells and CD4CD25regulatory T cells in CD4T cells.

RESULTSThe asthma group and the montelukast sodium group had significantly higher bronchial wall thickness and smooth muscle thickness at all time points compared with the blank group (P<0.05). At 8 weeks of intervention, the montelukast sodium group had significantly greater improvements in the above changes compared with the asthma group (P<0.05). Compared with the blank group, the asthma group and the montelukast sodium group had significant increases in Th17 cells (positively correlated with airway remodeling) and significant reductions in CD4CD25regulatory T cells (negatively correlated to airway remodeling) at all time points (P<0.05). At 8 weeks of intervention, the montelukast sodium group had a significant reduction in the number of Th17 cells and a significant increase in the number of CD4CD25regulatory T cells compared with the asthma group (P<0.05).

CONCLUSIONSMontelukast sodium intervention can alleviate airway remodeling and achieve better improvements over the time of intervention. The possible mechanism may be related to the improvement of immunologic derangement of CD4CD25regulatory T cells and inhibition of airway inflammation.

Acetates ; pharmacology ; Airway Remodeling ; drug effects ; Animals ; Asthma ; drug therapy ; immunology ; Female ; Lung ; pathology ; Mice ; Mice, Inbred BALB C ; Quinolines ; pharmacology ; T-Lymphocytes, Regulatory ; immunology ; Th17 Cells ; immunology