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

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 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 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

OBJECTIVE: To investigate the expression levels of Th9, Th17 and Treg cells in peripheral blood of patients with chronic rhinosinusitis with nasal polyps (CRSwNP), and explore the role of Th9, Th17 and Treg cells in the progression of CRSwNP. METHOD: Forty-six cases with CRSwNP served as an experimental group, while 22 cases with simple nasal bleeding or nasal septum deviation served as a control group. The peripheral blood of patients in both groups was collected and analyzed. (1) Using flow cytometry (FCM) to detect the expression rates of Th9, Th17 and Treg cells in peripheral blood. (2) Using qRT-PCR to detect the expression of relevant transcription factor of Th9, Th17 and Treg cells (IL-9mRNA, PU. 1, IRF-4, RoRc, and Foxp3). (3) Using SPSS16.0 to analyse the differentiations and the revelance among these three cells. RESULT: (1) The expression rates of Th9 and Th17 cells in patients with CRSwNP (1.29% ± 0.18%, 4.03% ± 0.69%) was higher than the control group (0.45% ± 0.14%, 1.35% ± 0.26%). But the expression rates of Treg cells in the experimental group (2.98% ± 0.13%) was significantly lower than the control group (5.44% ± 0.57%). The differences were statistically significant (P < 0.05). (2) The expression of revelant transcription factor (IL-9mRNA, PU.1, IRF-4, RoRc) in NP group was also higher than the control group. The expression of Foxp3 in the control group was higher than NP, the differences both were statistically significant (P < 0.05). (3) The difference between Th9 and Th17 in patients with NP was not significant (P > 0.05), and the negative correlation was found between Th17 and Treg (r = -0.549, P < 0.05). CONCLUSION The high expression level of Th9 and Th17 cells might promote the development of NP, whereas the low expression level of Treg cells might further aggravate the occurrence of NP. The main function of the imbalance of Th17/Treg cells may be immune regulation in the pathogenesis of nasal polys.
Case-Control Studies ; Cell Differentiation ; Disease Progression ; Epistaxis ; Flow Cytometry ; Forkhead Transcription Factors ; metabolism ; Humans ; Nasal Polyps ; immunology ; pathology ; Nasal Septum ; abnormalities ; Rhinitis ; immunology ; pathology ; Sinusitis ; immunology ; pathology ; T-Lymphocytes, Regulatory ; cytology ; Th17 Cells ; cytology ; Transcription Factors ; metabolism

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

BACKGROUND: Interleukin-17 (IL-17)-producing T helper (Th) 17 cells are considered as a new subset of cells critical to the development of rheumatoid arthritis (RA). We aimed to investigate the distribution of Th1 and Th17 cells and their association with disease activity, and determine the Th17-related cytokine levels in the peripheral blood of RA patients. METHODS: Peripheral blood mononuclear cells from 55 RA and 20 osteoarthritis (OA) patients were stimulated with mitogen, and the distributions of CD4+Interferon (INF)+IL-17- (Th1 cells) and CD4+INF-IL-17+ (Th17 cells) were examined by flow cytometry. Serum levels of IL-6, IL-17, IL-21, IL-23, and tumor necrosis factor (TNF)-alpha were measured by ELISA. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were recorded. The 28-joint disease activity score (DAS28) was also assessed. RESULTS: The median percentage of Th17 cells was higher in RA patients than in OA patients (P=0.04), and in active than in inactive RA (P=0.03), whereas that of Th1 cells was similar in both groups. Similarly, the levels of IL-17, IL-21, and IL-23 were detected in a significantly higher proportion of RA patients than OA patients and the frequencies of detectable IL-6, IL-17, and IL-21 were higher in active RA than in inactive RA group. The percentage of Th17 cells positively correlated with the DAS28, ESR, and CRP levels. CONCLUSIONS: These observations suggest that Th17 cells and Th17-related cytokines play an important role in RA pathogenesis and that the level of Th17 cells in peripheral blood is associated with disease activity in RA.
Adult ; Aged ; Arthritis, Rheumatoid/blood/metabolism/*pathology ; Blood Sedimentation ; C-Reactive Protein/analysis ; Cytokines/blood ; Female ; Humans ; Male ; Middle Aged ; Osteoarthritis/blood/metabolism/pathology ; Severity of Illness Index ; Th1 Cells/cytology/immunology/metabolism ; Th17 Cells/*cytology/immunology/metabolism

The aim of this study was to evaluate whether the Th17 and Treg cell infiltration into allograft tissue is associated with the severity of allograft dysfunction and tissue injury in acute T cell-mediated rejection (ATCMR). Seventy-one allograft tissues with biopsy-proven ATCMR were included. The biopsy specimens were immunostained for FOXP3 and IL-17. The allograft function was assessed at biopsy by measuring serum creatinine (Scr) concentration, and by applying the modified diet in renal disease (MDRD) formula, which provides the estimated glomerular filtration rate (eGFR). The severity of allograft tissue injury was assessed by calculating tissue injury scores using the Banff classification. The average numbers of infiltrating Treg and Th17 cells were 11.6 +/- 12.2 cells/mm2 and 5.6 +/- 8.0 cells/mm2, respectively. The average Treg/Th17 ratio was 5.6 +/- 8.2. The Treg/Th17 ratio was significantly associated with allograft function (Scr and MDRD eGFR) and with the severity of interstitial injury and tubular injury (P < 0.05, all parameters). In separate analyses of the number of infiltrating Treg and Th17 cells, Th17 cell infiltration was significantly associated with allograft function and the severity of tissue injury. By contrast, Treg cell infiltration was not significantly associated with allograft dysfunction or the severity of tissue injury. The results of this study show that higher infiltration of Th17 cell compared with Treg cell is significantly associated with the severity of allograft dysfunction and tissue injury.
Acute Disease ; Creatinine/metabolism ; Forkhead Transcription Factors/metabolism ; Graft Rejection/*etiology/pathology ; Humans ; Immunoenzyme Techniques ; Interleukin-17/*metabolism ; Kidney Transplantation/*adverse effects ; Retrospective Studies ; T-Lymphocytes, Regulatory/*immunology/pathology ; Th17 Cells/*immunology/pathology ; Transplantation, Homologous