Related Cytokines In Peripheral Blood Research Articles

Effects of SOCS1-overexpressing dendritic cells on Th17- and Treg-related cytokines in COPD mice

BackgroundIn this study, we established a chronic obstructive pulmonary disease (COPD) model by stimulating mice with cigarette smoke, and observed the effects of dendritic cells (DCs) overexpressing SOCS1 on Th17, Treg and other related cytokines in peripheral blood, bronchoalveolar lavage fluid and lung tissues of COPD mice.MethodsAfter successfully transfecting DCs with overexpressing SOCS1 (DC-SOCS1), the mice were injected with DC-SOCS1 (1 × 106), DC-SOCS1 (2 × 106) and immature DCs (1 × 106) via tail vein on days 1 and 7 of COPD fumigation modeling. After day 28 of modeling, the peripheral blood, BALF and lung tissue samples were extracted from the mice, and the changes of DCs, Th17 and Treg cells and related cytokines were detected by immunohistochemistry, immunofluorescence, HE staining, flow cytometry and ELISA.ResultsThe results showed that DC-SOCS1 was able to reduce the secretion of pro-inflammatory factors and increase the anti-inflammatory factors in the COPD mice, and the effect of high concentration (2 × 106 DC-SOCS1) was better than low concentration (1 × 106 DC-SOCS1). Moreover, the intervention effect was significant on day 1 compared with day 7. In the mice injected with DC-SOCS1, the expression of CD83, IL-4, Foxp3, and CCR6 was increased on day 1 than those on day 7, while IL-17 and IFN-γ was decreased.ConclusionsIntervention of COPD mice with high concentrations of DCs-SOCS1 reduced pro-inflammatory factor secretion and attenuated the inflammatory response in COPD.Trial registration Not applicable.

Novel Th17 Lymphocyte Populations, Th17.1 and PD1+Th17, are Increased in Takayasu Arteritis, and Both Th17 and Th17.1 Sub-Populations Associate with Active Disease.

PurposeWe evaluated T helper lymphocyte profile, including novel Th17 subsets Th17.1 (secrete IFN-γ, associate with corticosteroid resistance) and PD1+Th17 (secrete TGF-β1, implicated in fibrosis), and related cytokines in peripheral blood of Takayasu arteritis (TAK).Materials and MethodsWe evaluated circulating Th1, Th2, Th17, Th17.1, PD1+CD4+ T lymphocytes, PD1+Th17, and Treg lymphocytes, inflammatory (IFN-γ, IL-4, IL-6, IL-17A, IL-23, IL-1β, TNF-α) and regulatory (IL-10, TGF-β1) cytokines in peripheral blood of TAK (n = 57; median age 35 (interquartile range 26–45) years; 40 females) in a cross-sectional design. We studied inflammatory and regulatory cytokines in culture supernatant of peripheral blood mononuclear cells (PBMCs) from TAK following stimulation with anti-CD3/anti-CD28 and their modulation by tacrolimus (immunosuppressive) with/without tadalafil (anti-fibrotic). Furthermore, we followed up immunosuppressive-naïve active TAK (n = 16) and compared T helper lymphocyte populations and cytokines before and after immunosuppressive therapy. Healthy controls (HC, n = 21) and sarcoidosis (disease control, n = 11) were compared against TAK.ResultsTAK had higher Th17, Th17.1 and PD1+Th17 lymphocytes than HC (p < 0.001), and higher PD1+CD4+ T lymphocytes than sarcoidosis (p < 0.001). Th17 lymphocytes associated with active TAK after multivariable-adjusted logistic regression (p = 0.008). TAK had greater cytokine secretion from PBMCs (IFN-γ, IL-17A, IL-10 versus HC; IL-6, TNF-α, IL-1β versus HC or sarcoidosis) (p < 0.05). In-vitro, PBMCs from TAK showed reduced secretion of all inflammatory cytokines with tacrolimus, with synergistic reduction in IL-17A, IL-6, IL-1β and IL-10 following addition of tadalafil to tacrolimus. Serial follow-up of immunosuppressive-naïve TAK (n = 16) showed reduction in serum IL-6 and TGF-β1 (p < 0.05) and IL-6 in culture supernatant (p < 0.05) following immunosuppressive therapy.ConclusionNovel Th17 sub-populations (Th17.1 and PD1+Th17) are elevated in TAK. Th17 lymphocytes associate with active TAK. In-vitro experiments on cultured PBMCs suggest promise for further evaluation of a combination of immunosuppressive tacrolimus with anti-fibrotic tadalafil (or other anti-fibrotic therapies) in clinical trials of TAK.

Expression of Th17/Treg Cells in Peripheral Blood and Related Cytokines of Patients with Ulcerative Colitis of Different Syndrome Types and Correlation with the Disease.

Objective To explore the expression of helper T cells 17 (Th17)/regulatory T cells (Treg) in peripheral blood and related cytokines of patients with different types of ulcerative colitis (UC) and analyze their correlation with the disease. Methods From January 2018 to December 2019, 53 patients diagnosed with UC in our hospital were selected. According to their medical syndromes, they were divided into the damp-heat internal accumulation group (n = 35) and the spleen-kidney yang deficiency group (n = 18). 21 healthy volunteers were selected as the control group. The Mayo scoring standard was used to determine the severity of the patient's condition. The expression levels of Th17/Treg cells and related cytokines in peripheral blood were compared between the groups. Pearson correlation was used to analyze the correlation between the ratio of Th17 and Treg cells in the peripheral blood of UC patients and the ratio of TH17/Treg with Mayo score. Results The peripheral blood Th17 cell ratio and Th17/Treg ratio of the damp-heat internal accumulation and spleen-kidney yang deficiency group were higher than those of the control group; the Treg cell ratio was lower than that of the control group; the peripheral blood Th17 cell ratio and Th17/Treg ratio of the damp-heat internal accumulation group were higher those of the spleen-kidney yang deficiency group; and the proportion of Treg cells was lower than that of the spleen-kidney yang deficiency group (P < 0.05). The expression levels of serum IL-6, IL-17, IL-22, and TNF-α in the damp-heat internal accumulation and spleen-kidney yang deficiency group were higher than those of the control group; IL-10 and TGF-β were lower than those of the control group; the levels of serum IL-6, IL-17, IL-22, and TNF-α in the damp-heat internal accumulation group were higher than those of the spleen-kidney yang deficiency group; and both IL-10 and TGF-β were lower than those of the spleen-kidney yang deficiency group (P < 0.05). The peripheral blood Th17 cell ratio and Th17/Treg ratio in the moderately active period group and severely active period group were higher than those of the lightly active period group; the Treg cell ratio was lower than that of the lightly active period group; the peripheral blood Th17 cell ratio and Th17/Treg ratio in the severely active period group were higher than those in the moderately active period group; and the proportion of Treg cells was lower than that of the moderately active period group. Pearson correlation analysis showed that the proportion of Th17 cells and Th17/Treg in peripheral blood of UC patients were both positively correlated with Mayo score (r = 0.762, r = 0.777, P < 0.001). Treg was negatively correlated with Mayo score (r = −0.790, P < 0.001). Conclusion There are differences in the expression of peripheral blood Th17/Treg cells and related cytokines among UC patients with different syndromes, and the damp-heat content is the most significant. The higher the ratio of Th17 cells in peripheral blood and the degree of Th17/Treg imbalance, the lower the ratio of Treg cells, and the more severe the condition of UC patients, which can provide a preliminary quantitative basis for the TCM classification and severity of the diagnosis of UC.

Expression of Semaphorin 4A and Neuropilin-1 in Peripheral Blood of Patients with Rheumatoid Arthritis and Their Relationship with Regulatory T Cell/Helper T Cells 17 Balance

To investigate the expression of semaphorin 4A and neuropilin-1 in peripheral blood of patients with rheumatoid arthritis and their relationship with the regulatory T cell/helper T cell 17 balance. 80 patients with rheumatoid arthritis who were treated in the Department of Rheumatology and Immunology of a third class hospital from October 2018 to October 2020 were selected as the rheumatoid arthritis group and another 80 healthy persons who underwent physical examination in the same period were selected as the control group. The expression levels of semaphorin 4A, neuropilin-1 and cytokines associated with regulatory T cell and helper T cells 17 in peripheral blood serum were detected by enzyme linked immunosorbent assay. The proportion of regulatory T cell and helper T cells 17 in peripheral blood mononuclear cells was detected by XTG-1600U flow cytometry and the ratio of regulatory T cell/helper T cells 17 was calculated. Pearson test was used to analyze the relationship between the expression level of semaphorin 4A, neuropilin-1 and regulatory T cell/helper T cells 17 ratio and related cytokines in peripheral blood serum of patients with rheumatoid arthritis. The expression levels of semaphorin 4A and neuropilin-1 in peripheral blood serum in rheumatoid arthritis group were significantly higher than those in control group (p<0.05). The proportion of regulatory T cell cells and regulatory T cell/helper T cells 17 ratio in peripheral blood mononuclear cells were significantly lower than those in control group (p<0.05). The proportion of helper T cells 17 cells in peripheral blood mononuclear cells was significantly higher than that in control group (p<0.05). The expression levels of transforming growth factor-β and interleukin-10 in peripheral blood of patients with rheumatoid arthritis were significantly lower than those in control group, while the expression levels of interleukin-23, interleukin-17 and interleukin-6 in peripheral blood serum were significantly higher than those in control group. Correlation analysis showed that the expression levels of semaphorin 4A and neuropilin-1 in peripheral blood serum were negatively correlated with the ratio of regulatory T cell/helper T cells 17 and the expression levels of transforming growth factor-β and interleukin-10 in peripheral blood serum, but positively correlated with the expression levels of interleukin-23, interleukin-17 and interleukin-6 in peripheral blood serum in patients with rheumatoid arthritis. The expression of semaphorin 4A and neuropilin-1 in peripheral blood serum of patients with rheumatoid arthritis is high and the ratio of regulatory T cell/helper T cells 17 is decreased. The expression level of semaphorin 4A and neuropilin-1 in peripheral blood serum may affect the balance of regulatory T cell/helper T cells 17 in patients with regulatory T cell/helper T cells 17.

Low frequency of IL-10-producing B cells and high density of ILC2s contribute to the pathological process in Graves’ disease, which may be related to elevated-TRAb levels

IL-10-producing B Cells (B10) is a functionally defined regulatory B-cell subset. It plays an important role in the control of inflammation and autoimmune diseases, although it is present at low numbers in peripheral blood. Graves’ disease is an autoimmune disease characterized by the production of autoantibodies such as TRAb. ILC2s maintains Th2 polarization state by producing type-II cytokines. It is not clear whether the level of autoantibody is related to ILC2s and B10 cells in Graves’ disease. In this study, we analyzed the frequencies of B10, Treg cells and ILC2s, as well as the expression of related cytokines in peripheral blood from patients with Graves' disease and evaluated the correlation between B10 cell numbers and autoantibodies level. Our data showed that the frequency of B10 or Treg cells was significantly decreased in peripheral blood mononuclear cells from Graves' disease patients, while the percentage of ILC2s cells was increased; the levels of cytokine IL-5, IL-13 and related transcription factor RORα were up-regulated. Autoantibodies analysis also showed that high level of TRAb was accompanied by low rates of B10 cells in patients, there was a negative correlation trend. In addition, the analytical data from mouse disease models also showed similar results. It indicates that B10 cells may affect the production of TRAb by negative regulation of Th2 cells, while ILC2s can promote the production of autoantibodies such as TRAb by maintaining the dominant response state of Th2 cells.

Changes of IL-17 and related cytokines in peripheral blood and intestinal mucosa of children with abdominal Henoch-Schonlein purpura

Changes of IL-17 and related cytokines in peripheral blood and intestinal mucosa of children with abdominal Henoch-Schonlein purpura

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.

Expression of Treg cells, TH17 cells and related cytokines in peripheral blood of patients with severe hand-foot-mouth disease caused by Enterovirus 71 virus

Objective To investigate the changes of Treg cells, Th17 cells and related cytokines in peripheral blood of patients with severe hand-foot-mouth disease(HFMD) in the initial stage of infection caused by Enterovirus 71 virus. Methods Thirty-five cases of severe HFMD children in the Fifth Hospital of Shijiazhuang from May 2013 to December 2013 were selected as the research subjects, including 27 cases of severe formed group and 8 cases of danger severe formed group.The frequencies of Th17 cells(CD3+ CD8-IL-17+ ) and Treg cells(CD4+ CD25+ Foxp3+ ) in peripheral blood were detected by flow cytometry in patients with severe HFMD and 31 healthy children(control group). Moreover the serum levels of interleukin 6(IL-6), interleukin 17(IL-17), interleukin 10(IL-10), interleukin 23(IL-23), and human transforming growth factor β 1 (TGF-β 1) were measured by ELISA. Results As compared with those in control group, the frequencies of Treg cells, ratio of Treg/Th17, serum levels of TGF-β1, IL-10 in severe HFMD groups were significantly decreased(F=23.23, 30.88, 10.766, 11.680 respectively; P<0.05). However the frequency of Th17 cells, serum levels of IL-6, IL-17, IL-23 in severe HFMD groups were significantly increased(F=646.81, 5.904, 10.557, 3.490 respectively; P<0.05). Conclusion The changes of Treg and Thl7 cells and related cytokines appear in peripheral blood of patients with HFMD in the initial stage of infection caused by Enterovirus 71 virus.The frequency of Treg cell is decreased, however, the frequency of Thl7 cells frequency is increased, as a result, which may spread inflammatory reaction and cause complication. Key words: Hand-foot-mouth disease; Treg cells; Thl7 cells; Cytokines

Circulating T-helper 17 cells and associated cytokines in psoriasis.

Recently, a new population of IL-17-producing CD4 T helper (Th) cells, named Th17, was identified and shown to be involved in various inflammatory and autoimmune diseases, including psoriasis. To determine the frequency of Th17 cells and related cytokines in peripheral blood of patients with psoriasis, and to analyse their association with disease severity. This was a prospective study comprising 34 patients with psoriasis and 24 healthy controls. Clinicoepidemiological details of patients were recorded, and severity of psoriasis was assessed by means of the Psoriasis Area and Severity Index. Circulating Th1 and Th17 cells in untreated patients with psoriasis and healthy controls were quantified by flow cytometry. In sera collected from patients with psoriasis and healthy controls, concentrations of IL-17A and IL-23 were examined by ELISA. Increased frequencies of CD4+ IL-17A+ T cells were seen in peripheral blood of patients with psoriasis vulgaris (P < 0.001). Although serum IL-17A and IL-23 concentrations were higher in patients with psoriasis than in controls, the results did not reach statistical significance. We could not find any correlation between the studied T cells or related cytokines and the disease severity. Increased serum levels of circulating Th17 cells and related cytokines may contribute to the cutaneous pathology of psoriasis, as well as the inflammatory process that is a hallmark of psoriasis.

Expression of Treg/Th17 cells as well as related cytokines in patients with inflammatory bowel disease.

Objective:To investigate the expressions of peripheral regulatory T cells (Treg) and T helper cells (Th17) as well as related cytokines in peripheral blood of patients with inflammatory bowel disease (IBD).Methods:One hundred four cases of IBD patients admitted in our hospital were selected for this study. One hundred cases of people receiving healthy physical examination were included in the control group in the corresponding period. The levels of CD4+CD25+Treg and Th17 subsets were analyzed in peripheral blood of two groups using flow cytometry. The expressions of IL-10, TGF-β1, IL-17 and IL-23 mRNA and protein were detected using real-time fluorescence quantitative PCR and ELISA.Results:Compared with the control group, the proportion of Treg in peripheral blood was decreased significantly in observation group (P<0.05), the proportion of Th17 cells was increased significantly (P<0.05), and Treg/Th17 was decreased significantly (P<0.05). Compared with the control group, the expressions of IL-10 and TGF-β1 mRNA and protein in peripheral blood of patients were significantly down-regulated in observation group, while the expressions of Th17 cytokines IL-17 and IL-23 mRNA and protein were significantly increased (P<0.05).Conclusion:The proportion of Th17 and increased cytokine level suggested the inflammatory level was higher in IBD patients. The down regulations of Treg and cytokine suggested that the immunosuppression function was down-regulated in IBD patients, and the disproportionality might be one of the mechanisms of IBD.