scholarly journals Endometriotic Peritoneal Fluid Stimulates Recruitment of CD4+CD25highFOXP3+ Treg Cells

2021 ◽  
Vol 10 (17) ◽  
pp. 3789
Author(s):  
Joanna Olkowska-Truchanowicz ◽  
Alicja Sztokfisz-Ignasiak ◽  
Aneta Zwierzchowska ◽  
Izabela Janiuk ◽  
Filip Dąbrowski ◽  
...  

Endometriosis is a common gynecological disorder characterized by the presence of endometrial-like tissue outside the uterus. The disease is associated with disturbed local and systemic immunity. It has been reported that the proportion of CD4+CD25highFOXP3+ Treg cells may be significantly increased in the peritoneal fluid of patients with endometriosis. Therefore, the aim of our study was to investigate whether the proportions of Treg cells in the peritoneal cavity of patients with endometriosis are related to the chemotactic and stimulatory activity of the local peritoneal milieu. The peritoneal fluid was collected from 13 women with ovarian endometriosis and 12 control women without the disease. T cell populations were analyzed by flow cytometry, cytokines and chemokines were evaluated using the cytometric bead kit, and cell chemotaxis was studied by cell migration assay. We confirmed that the proportions of Treg cells are increased in the peritoneal fluid of women with endometriosis as compared to the control women. Endometriosis was also associated with elevated concentrations of IL-6, IL-10, and TGF-β1/2 as well as CCL20, CXCL8, CXCL9, and CXCL10. We did not reveal any changes in the proportion of peritoneal Th17 cells and concentrations of IL-17A. Peritoneal Treg cells positively correlated with concentrations of TGF-β, IL-10, and CCL20. Endometriotic peritoneal fluid stimulated chemotaxis of both CD4+ and Treg cells. This chemotactic activity positively correlated with concentrations of CCL20. CCL20 stimulated the migration of Treg cells, and the chemotactic activity of the endometriotic peritoneal fluid was inhibited by neutralizing anti-CCL20 antibodies. These results imply that increased proportions of the peritoneal Treg cells in women with endometriosis may result from attraction and activation by local chemokines and cytokines, especially CCL20 and TGF-β. Since Treg cells contribute to the immunopathogenesis of endometriosis, their chemotaxis and activation may be considered as a target for therapeutic intervention.

2019 ◽  
Vol 22 (4) ◽  
pp. 232-237 ◽  
Author(s):  
Jihong An

Objective: This study aims to investigate the expression and clinical significance of Th17 cells and related factors in peripheral blood of patients with Autoimmune Hepatitis (AIH). Methods: A retrospective selection of 100 patients with AIH were included as a study group, and 100 healthy volunteers in the outpatient clinic were selected as the control group. The levels of IL- 17, IL-6, IL-21 and TNF-α in peripheral blood of all subjects were detected by enzyme-linked immunosorbent assay and the frequency of Th17 cells and Treg cells was detected by flow cytometry. Results: Results showed that the study group had higher levels of serum total bilirubin (TBil), alkaline phosphatase (ALP), γ -glutamyltranspeptidase (γ-GT), immunoglobulin G (IgG), immunoglobulin M (IgM), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) than the control group, as well as higher levels of IL-17, IL-6, IL-21 and TNF-α in serum. The frequency of Th17 cells in peripheral blood was higher in the study group, while the frequency of Treg cells was lower. Also, serum IL-17, TNF-α levels and Th17 cells frequency were positively correlated with ALT and AST, whereas Treg cells frequency were negatively correlated with ALT and AST levels. Conclusion: Our finding demonstrates that Th17 cell frequency and their related factors IL-17 and TNF-α, are associated with liver damage, which might be used to monitor AIH disease severity.


2013 ◽  
Vol 28 (8) ◽  
pp. 1079-1086 ◽  
Author(s):  
L. Ma ◽  
H.-B. Xue ◽  
X.-H. Guan ◽  
C.-M. Shu ◽  
F. Wang ◽  
...  

2016 ◽  
Vol 29 (4) ◽  
pp. 696-706 ◽  
Author(s):  
Jun Shi ◽  
Yu Liu ◽  
Shihai Yan ◽  
Daonan Yan

Allergic rhinitis (AR) is an inflammatory disease with a hypersensitivity response to environmental stimulus. The aim of this study was to evaluate the effect of Yiqi Wenyang Fang (YWF) on AR and investigate the underlying mechanism. A total of 48 female Sprague-Dawley rats were randomly divided into six groups (normal control, model control, YWF at low dose, YWF at median dose, YWF at high dose, and loratadine). Rats were injected with antigen for sensitization. Then, rats in the YWF groups were treated with different dose of YWF for 28 days. Loratadine was used as a positive control. Number of sneezes, degree of runny nose, nasal rubbing movements, and tissue damage were scored. The protein and mRNA expression of Foxp3 were determined by western blot and real time-PCR analysis, respectively. Flow cytometry was used to detect the number of CD4+CD25+Foxp3+ Treg cells. The content of interleukin (IL)-10, transforming growth factor β1 (TGF-β1), IL-13, and IL-4 in the serum were detected by enzyme-linked immunosorbent assay (ELISA). Scores of symptoms were significantly reduced and nasal mucosa damage was alleviated after YWF administration. YWF increased the expression of Foxp3, IL-10, TGF-β1, and number of CD4+CD25+Foxp3+ Treg cells which were reduced by antigen injection. The expression levels of IL-13 and IL-4 were increased after antigen administration while decreased after YWF treatment. YWF may ameliorate AR through inhibiting inflammatory response and promoting Foxp3 expression.


2009 ◽  
Vol 36 (8) ◽  
pp. 1730-1736 ◽  
Author(s):  
ANKIT MAHENDRA ◽  
RAMNATH MISRA ◽  
AMITA AGGARWAL

Objective.A Th1 biased immune response in synovial fluid has been reported in children with polyarticular and extended oligoarticular-type juvenile idiopathic arthritis (JIA). We investigated T cell phenotypes including Th1, Th2, Th17, and Treg with emphasis on Th17 and Treg, in order to differentiate cytokines in the enthesitis-related arthritis (ERA) form of JIA.Methods.The frequencies of Th1, Th2, Th17, and Treg cells were determined by flow cytometry in peripheral blood (PB) and synovial fluid from patients with ERA and healthy subjects. Levels of interleukin 1ß (IL-1ß), IL-6, IL-21, IL-23, and transforming growth factor ß (TGF-ß), cytokines that influence Th17 lineage cells, were measured in paired plasma and synovial fluid (SF) samples by ELISA. Frequencies are expressed as percentages and cytokine levels as pg/ml.Results.There were no differences in blood samples in the frequency of Th1, Th2, Th17, and Treg cells between patients and controls. In paired samples, the median frequency of CD4+IFN-γ+ (20.49 vs 4.03; p < 0.005) and CD4+IL-17+ (2.27 vs 0.57; p < 0.01) cells was significantly higher in SF compared to PB, respectively; whereas the frequency of CD4+IL-4+ (1.79 vs 2.29; p < 0.04) cells was significantly reduced in the SF compared to PB. There was no difference in the frequency of regulatory T cells. Patients receiving methotrexate had fewer Th2 cells, whereas the Childhood Health Assessment Questionnaire score had a negative association with the frequency of Treg. Median levels of IL-1ß (p < 0.008), IL-6 (p < 0.0001), and IL-17 (p < 0.0001) were higher in SF than in plasma and levels of TGF-ß were lower (p < 0.001). Levels of IL-21 were similar in SF and plasma, whereas IL-23 was undetectable.Conclusion.In patients with ERA, peripheral blood Th1, Th2, Th17, and Treg cells were unchanged, but Th1 and Th17 cells were increased and Th2 cells were reduced in the SF compared to blood. Elevated IL-1ß and IL-6 in SF may be responsible for increased Th17 cells.


2017 ◽  
Vol 18 (7) ◽  
pp. 800-812 ◽  
Author(s):  
Jing Geng ◽  
Shujuan Yu ◽  
Hao Zhao ◽  
Xiufeng Sun ◽  
Xun Li ◽  
...  

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Leihua Weng ◽  
Xiang Chen ◽  
Yun Xu

Background: Despite unclear pathogenesis, previous studies have suggested immune responses may play a pivotal role in the process of Moyamoya disease (MMD), a rare cerebrovascular occlusive disorder. The objective of this study is aimed to explore the change of peripheral Treg/Th17 in MMDpatients and whether the change is associated with pathogenesis of MMD. Methods: In the present study, we collected 26 MMD patients diagnosed by angiography according to the diagnostic criteria of definitive MMD and recruited 32 healthy volunteers. To explore the balance of peripheral Treg/Th17 in MMD patients, lymphocytes in peripheral blood were harvested and flow cytometry was used to measure the percentage of Treg and Th17in CD4+ Tcells, respectively. Meanwhile, relevant cytokines in serum were measured to evaluate the function of Treg and Th17 cells. Results: According to Suzuki’s angiographic staging of moyamoya disease, patients were divided into subgroups of the preliminary-term, medium-term and late-term. Cerebral hemorrhage is thefirstsymptom of onset occuringin half of patients, followed bycerebral ischemia.Our data revealed that both the percentage of Treg and Th17 cells in peripheral blood lymphocytes was increased in MMD patients compared with volunteer group. Meanwhile, the levels of IL-6, IL-10,IL-12, IL-17, TNF-α, VEGF and TGF-β in serum were significantly increased in MMD patients. In this study, the level of HMGB-1, a middle-late period inflammation biomarker, in serum of MMD patients is obviously elevated compared with volunteers. However, the ratio of Treg/Th17 had no significant difference in MMD patients compared to healthy volunteers. Intriguingly, our data revealed that ratio of Treg/Th17 was significantly increased in late-term MMD patients compared with medium-term patients as evidenced by elevated percentage of Treg cells.. In addition, TGF-β level in later-term MMD patients was significantly higher than this in medium-term MMD patients. No difference was observed in the way of onset and gender between two groups. Conclusion: Enhanced peripheral Treg and Th17 in MMD patients suggested that there may be an immunological component in the pathogenesis of MMD. Peripheral Treg may be associated with pathological process of MMD.


2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Zhigang Wang ◽  
Xueting Cai ◽  
Zhonghua Pang ◽  
Dawei Wang ◽  
Juan Ye ◽  
...  

Background. Yupingfeng Pulvis (HFBP) had played an active role in many diseases, especially respiratory tract infections. Exploring the possible prevention mechanism of HFBP may provide new ideas in clinical applications for this well-known herbal formula.Purpose. To study the possible mechanisms of therapy effect of HFBP on asthma mice via regulating the balance of Tregs and Th17 cells.Method. The female BALB/c mice were divided into five groups: control group, model group, prednisone (5.5 mg/kg) group, and 22 g/kg HFBP and 44 g/kg HFBP groups. Ovalbumin was used to make the asthma model of mice; the drug was ig administered daily after atomization for consecutive 15 d. The mice were killed after the last administration. The paraffin-embedded tissue sections of the lungs were stained by H&E. Tregs and Th17 cells in bronchoalveolar lavage fluid were detected by flow cytometry. IL-4, TGF-β, and TNF-αin the serum were detected by ELISA assay.Results. HFBP could alleviate the inflammation in the lung tissue of mice, decrease the proportion of Th17 cells, and increase the proportion of Treg cells in bronchoalveolar lavage fluid. HFBP could decrease IL-4 and TNF-αlevel and increase TGF-βlevel in blood.Conclusion. HFBP could treat the asthma through impacting the balance of Th17 cells and Treg cells as well as the levels of related inflammatory cytokines in asthma mice.


2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Bo Nie ◽  
Xue Li ◽  
Yi Wei ◽  
Meng Chen ◽  
Jingwei Zhou ◽  
...  

In traditional Chinese medicine (TCM), xianfanghuomingyin (XFHM) is used to treat autoimmune diseases, including rheumatoid arthritis (RA). Here, we studied the mechanisms underlying its treatment effects, especially its anti-inflammatory effects in a collagen-induced arthritis (CIA) mouse model. We found that cartilage destruction and pannus formation were alleviated by treatment with XFHM. The abnormal differentiation of Th1 and Th17 cells was downregulated significantly by XFHM, and Th2 and Treg cells were upregulated. Moreover, the expression levels of specific cytokines and transcription factors related to Th1 cells (interferonγ[IFNγ], T-bet) and Th17 cells (interleukin- [IL-] 17) and the nuclear receptor retinoic acid receptor-related orphan receptor-gamma (RORγ) were downregulated. Serum IL-4 and GATA-3, which contribute to Th2 cells differentiation, increased significantly after XFHM administration. These results indicate that XFHM can restore the balance of T lymphocytes and reestablish the immunological tolerance to inhibit autoinflammatory disorder of RA. Taken together, XFHM can be used as a complementary or alternative traditional medicine to treat RA.


2021 ◽  
Vol 23 (4) ◽  
pp. 767-774
Author(s):  
G. I. Krichevskaya ◽  
E. S. Sorozhkina ◽  
N. V. Balatskaya ◽  
I. G. Kulikova ◽  
A. E. Andryushin ◽  
...  

Behcet’s disease (BD) is a systemic autoinflammatory-autoimmune disease (chronic systemic vasculitis) of unknown etiology, almost 70% of patients develop uveitis. BD pathogenesis is complex, human herpesviruses (HHV) play an important role among infectious trigger factors. Ability of herpesviruses to modulate cytokine production and evade host’s immune response is known.Aim of the study was to assess the effect of Herpes simplex virus type 1, Herpes simplex virus type 2, Cytomegalovirus, Epstein-Barr virus on systemic levels of chemokines, pro- and anti-inflammatory cytokines in BD with and without uveitis. Serum samples were collected from 116 BD patients chronically infected with HHV and examined in ELISA-test for markers of HHV reactivation (IgG-antibodies to immediate early HSV antigens 1, 2 and CMV, early EBV antigen). Concentration of IL-1β, IFNγ, MCP-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-12p70, IL-13, IL-18, TNFα, GMCSF, Eotaxin, GRO-α, IP-10, MIP-1α, MIP-1β, SDF-1α, RANTES detected in multiplex analysis. TGF-β1, TGF-β2 were measured in ELISA-test. Depending on presence and activity of uveitis 3 groups of patients with BD were identified: group 1 – active uveitis, group 2 – remission of uveitis, group 3 – BD without ocular manifestations. After serological study 2 subgroups were highlighted in each group: a) patients with antibody markers of reactivation of at least one HHV, b) patients chronically infected with HHV, without serological signs of reactivation. Mean level and detection rate of cytokines and chemokines in patients with active uveitis (1a, 1b) and in remission (2a, 2b) were compared with patients without eye damage (3a, 3b). Chronic HHV infection (subgroup “b”) was compared with reactivation (subgroup “a”). A significant increase of MCP-1/ CCL2, MIP-1α/CCL3, MIP-1β/CCL4, RANTES/CCL5, IP-10, SDF-1α chemokines in serum, as well as IFNγ, TGF-β1, and TGF-β2 was observed in patients with uveitis (regardless of their activity) and HHV reactivation compared to patients without uveitis. Our data indicate that systemic production of cytokines and chemokines in BD patients and uveitis could be affected by the activity of chronic herpesvirus infections, and the greatest changes are related to chemokines. 


2019 ◽  
Author(s):  
Sara M. Parigi ◽  
Srustidhar Das ◽  
Annika Frede ◽  
Rebeca F. Cardoso ◽  
Kumar Parijat Tripathi ◽  
...  

AbstractThe gastrointestinal microenvironment, dominated by dietary compounds and the commensal bacteria, is a major driver of intestinal CD4+ T helper (Th) cell differentiation. Dietary compounds can be sensed by nuclear receptors (NRs) that consequently exerts pleiotropic effects including immune modulation. However, how NRs regulate distinct intestinal Th subsets remain poorly understood. Here, we found that under homeostatic condition Liver X receptor (LXR), a sensor of cholesterol metabolites, controls RORγt+ Treg and Th17 cells in the intestine draining mesenteric lymph node (MLN). Mechanistically, while lack of LXR signaling in CD11c+ myeloid cells led to an increase in RORγt+ Treg, modulation of MLN Th17 was independent of LXR signaling in either immune or epithelial cells. Of note, LXRα modulated only the Th17 cells, but not RORγt+ Treg in the MLN and horizontal transfer of microbiota between LXRα−/− and WT mice was sufficient to partially increase the MLN Th17 in WT mice. While LXRα deficiency increased the abundance of Ruminococcaceae and Lachnospiraceae bacterial families compared to the WT littermates, microbiota ablation including ablation of SFB was not sufficient to dampen LXRα-mediated expansion of MLN Th17. Altogether, our results suggest that LXR modulates RORγt+ Treg and Th17 cells in the MLN through distinct mechanisms.


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