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Objective:To explore the expression level of interleukin-1 receptor-associated kinase-1 (IRAK1) in the peripheral blood of rheumatoid arthritis (RA) patients and analyze its relevance between disease activity and CD4 + T cell subsets. Methods:① The concentration of IRAK1 in the peripheral blood of 77 RA patients and 24 healthy controls were detected by enzyme linked immunosorbent assay (ELISA). ② The demo-graphic and clinical data of the RA group including disease activity score with 28 joints (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), CD4 + T cell subsets in peripheral blood. ③Independent sample t test or Mann-Whitney U test were used to compare the differences between the two groups. Spearman rank correlation test and multiple linear regression were used to analyze the correlation between IRAK1 expression level and clinical data. Results:① The IRAK1 level of the peripheral blood of RA patients was significantly higher than in the normal controls ( P<0.001). ② Compared to normal controls, the peripheral blood of the RA group, the absolute numbers and proportion of regulatory T (Treg) cells were decreased ( P<0.001), the absolute numbers and proportion of helper T (Th) 17 and the ratio of Th17/Treg were increased. Moreover, the ratio of Th17/Treg was also increased. ③ With the increase of disease activity in RA patients, the expression of IRAK1 also increased. The expression of IRAK1 in the peripheral blood of RA group was positively correlated with ESR, number of joints involved and DAS28, and had statistically significant difference between the two groups ( r=0.23, P<0.05; r=0.24, P<0.05; r=0.27, P<0.05). Meanwhile, it was sign-ificantly negatively correlated with the percentage of Treg ( r=-0.27, P<0.05), and was significantly positively correlated with the ratio of Th17/Treg ( r=0.23, P<0.05) . However, there was no significant correlation with the ratio of Th1/Th2( P>0.05). Furthermore, multiple stepwise regression analysis showed that the expression of IRAK1 in the peripheral blood of RA group was positively correlated with ESR and the number of joints involved ( β=0.34, P=0.019; β=0.27, P=0.004), and it was inversely correlated with percentage of Treg ( β=-0.23, P=0.047, R2=0.219). Conclusion:IRAK1 expression in the peripheral blood of RA patients is up-regulated and correlated with disease activity. The decrease of Treg and the imbalance of Th17/Treg caused by high expression of IRAK1 may be one of the main factors for the occurrence and development of RA. Interfering the expression of IRAK1 may be a potential new target for RA treatment.
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Objective:To investigate the dynamic change characteristics of peripheral blood interferon-γ (INF-γ), interleukin (IL)-4 levels and T helper cell (Th)1/Th2 balance in acute, subacute and restoration stages of children with Kawasaki disease (KD).Methods:Forty-one children with KD received treatment in Women′s and Children′s Hospital Affiliated of School of Medicine University of Electronic Science and Technology of China, Chengdu Women′s and Children′s Central Hospital from May 2017 to January 2020 were enrolled as the observation group, and 41 healthy children examinee from the same period were enrolled as the control group. Children with KD of the observation group were performed with tuberculin pure protein derivative (PPD) test when acute and restoration stage of KD respectively. Peripheral venous blood were drawn from KD children of the observation group in acute, subacute and restoration stage and the control group respectively, serum immune globulin IgG, IgA, IgM and IgE, serum IFN-γ and IL-4 levels were detected by enzyme linked immunosorbent assay (ELISA).Results:Positive rates of PPD test in the restoration stage was higher than that in the acute stage: 65.85%(27/41) vs.17.07%(7/41), there was statistical difference ( χ2 = 20.10, P<0.05). The levels of serum IgG, IgA, IgM and IgE in the acute stage , subacute stage and restoration stagewere gradually decreased ( P<0.05). The levels of serum IgG, IgA, IgM and IgE in the restoration stage and the control group had no significant differences ( P>0.05). The levels of serum IFN-γ and IFN-γ/IL-4 in the acute stage , subacute stage and restoration stage were gradually increased ( P<0.05), the level of IL-4 was gradually decreased ( P<0.05), but the levels of serum IFN-γ, IL-4 and IFN-γ/IL-4 in the restoration stage and the control group had no significant differences ( P>0.05). Conclusions:Among the children with KD in acute stage, serum level of IFN-γ is decreased while serum IL-4 level is increased, and Th1/Th2 balance shifts to Th2. Along with the stabilization of disease, the levels of serum IFN-γ and IL-4 are normalized, and Th1/Th2 balance presents a recovering trend and they almost recover to normal after entering the restoration stage.
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Na?ve CD4 + T cells differentiate into a variety of T helper (Th) subsets that secrete various cytokines to exert biological effects. Th22 cells, a novel identified CD4 + T cell subset, are distinct from Th1, Th2 and Th17 cell subsets. Th22 cells express chemokine receptors CCR4, CCR6 and CCR10, and secrete multiple cytokines such as IL-22, IL-13 and TNF-α, but not IL-17, IL-4 IFN-γ; and IL-22 is considered as major effector cytokine of Th22. The understanding on functions and differentiation mechanisms of Th22 cells have been constantly improved, and Th22 cells play important roles in human common viral infections. The article reviews the current advances about the characteristics, function, differentiation of Th22 cells, the roles of Th22 cells and the key molecules in several human common viral infections, which would provide novel immune strategies for the prevention and treatment of human viral infection.
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Objective:To investigate the effect of CD 8+ CD 25+ FoxP3 + regulatory T cell (Treg) expression levels in peripheral blood of pregnant women with premature rupture of fetal membranes(PROM) on immune function of helper T cells (Th) 1/Th2. Methods:Thirty cases of pregnant women with PROM (PROM group), 30 cases of normal pregnant women (normal pregnancy group) and 30 cases of normal non-pregnant women (non-pregnancy group) who treated in Binhai County People′s Hospital from September 2019 to May 2020 were collected. Peripheral blood of each group was collected and the proportion of CD 8+ CD 25+ FoxP3 + Treg was determined by flow cytometry. Peripheral blood mononuclear cells (PBMCs) were extracted and FoxP3 mRNA was determined by polymerase chain reaction (PCR). The levels of Th1-related cytokines interferon-γ (IFN-γ), interleukin (IL)-2, and Th2-related cytokines IL-10 and IL-4 were measured by Luminex liquid phase microarray. The effects of CD 8+ CD 25+ FoxP3 + Tregexpression on Th1/Th2 balance were analyzed. Results:The proportion of CD 8+ CD 25+ FoxP3 + Tregand the expression of FoxP3 mRNA in PROM groupand normal pregnancy group were lower than those in non-pregnancy group: (0.15 ± 0.03) %, (0.35 ± 0.09) % vs. (0.47 ± 0.11) %; 0.89 ± 0.11, 3.15 ± 0.67 vs. 3.75 ± 0.23 , the proportion of CD 8+ CD 25+ FoxP3 + Treg and the expression of FoxP3 mRNA in PROM groupwere lower than those in the normal pregnancy group , and the differences were statistically significant ( P<0.05). The levels of Th1-related cytokines IFN-γ and IL-2 in PROM group and normal pregnancy group were higher than those in non-pregnancy group, the level of Th2-related cytokines IL-4 was lower than that in non-pregnancy group , the levels of IFN-γ and IL-2 in PROM group were higher than those in normal pregnancy group, the level of IL-4 was lower than that in normal pregnancy group , and the differences were statistically significant ( P<0.05). In PROM group, the proportion of CD 8+ CD 25+ FoxP3 + Treg and the expression of FoxP3 mRNA in peripheral blood were negatively correlated with Th1-related cytokines IFN-γ ( r = - 0.413, -0.451, P<0.05) and IL-22 ( r = -0.645, -0.535, P<0.05), and were positively correlated with Th2-related cytokines IL-4 ( r = 0.558, 0.469, P<0.05). Conclusions:The proportion of CD 8+ CD 25+ FoxP3 + Treg in peripheral blood of pregnant women with PROM is lower, and the expression level of related FoxP3 mRNA is lower, which all affecte the Th1/Th2 immune balance and cause Th1 immune drift, which may be the related immune mechanism of PROM.
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Background: Immune factors play an important role in the pathogenesis of inflammatory bowel disease (IBD). Clinical studies have shown that tripterygium glycosides is effective for the treatment of IBD. Aims: To investigate the effect of tripterygium glycosides on differentiation and balancing of Th17/Treg cells in rats with experimental colitis. Methods: Experimental colitis was induced by TNBS-ethanol method in rats to evaluate the therapeutic effect of tripterygium glycosides. After intragastrically administered with normal saline (model group), tripterygium glycosides or mesalazine, respectively once a day for two weeks, the disease activity index (DAI) was assessed, and the colonic mucosal injury was examined macro- and microscopically. Mononuclear cells of mesenteric lymph nodes were extracted, and the levels of Th17/Treg-related cytokines in the supernatant were detected by ELISA method. The expression of proinflammatory cytokines in colon tissues was detected by immunohistochemistry. Results: The symptoms of experimental colitis were more severe in model group. DAI, gross morphological and histopathological score of colonic mucosal injury were significantly higher in model group than in tripterygium glycosides and mesalazine groups (P0.05). Compared with the model group, the levels of IL-23 and TNF-α in the supernatant of mesenteric lymph nodes mononuclear cells in mesalazine group, and the levels of IL-23, TNF-α and IL-6 in tripterygium glycosides group were significantly reduced (P0.05). In rats treated with mesalazine, the expression of IL-6 in colon tissues was down-regulated significantly (P<0.05). Conclusions: Tripterygium glycosides have the potential to inhibit the differentiation of Th17 cells and promote the differentiation of Treg cells in IBD. Regulating the imbalance of Th17/Treg cells might be one of the mechanisms of its therapeutic effect on IBD.
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Objective To study the expression of peripheral blood lymphocyte subsets in psoriatic arthritis (PsA) patients and the short-term efficacy of low doses of interleukin-2 (IL-2). Methods Ninety-five patients with PsA were enrolled as study subjects and 106 healthy people as control group. On the basis of conventional treatment, a total of 22 PsA patients were randomly selected and treated with low dose IL-2 (5 ×105 U/d, continuously used for 5 days, IH), and the disease condition and lymphocyte changes were observed. Flow cytometry was used to detect the absolute count of T subsets dominated by regulatory T cell(Treg) and T helper cell 17(Th17). Wilcoxon rank sum test, χ2 test and Spearman correlation analysis were used for statistical analysis. Results The absolute number of Th17 cells of PsA patients [7.2 (4.0, 12.8) cells/μl] was higher than that of the control group [5.9(4.0, 8.6) cells/μl] (Z=-1.997, P=0.046), the number of Treg cells [25 (17, 36) cells/μl] decreased compared with the control group [30 (23, 40) cells/μl] (Z=-2.957, Z=0.003), T/Treg [50 (36), 76)], B/Treg [7.6 (5.4, 11.5)], CD4+T/Treg [27 (21, 42)], CD8+T/Treg [20 (12, 30)], Th17/Treg [0.34(0.13, 0.51)], Th1/Treg [4.4(2.3, 7.2)], Th2/Treg [0.34(0.20, 0.53)], compared with control group T/Treg [40 (32, 54)], B/Treg [6.5 (4.2, 8.1)], CD4+T/Treg [20 (17, 25)], CD8+T/Treg [16 (11, 24)], Th17/Treg [0.19 (0.13, 0.31)], Th1/Treg [3.5 (1.8, 5.8)], Th2/Treg [0.24 (0.15, 0.39)] were significantly increased (Z=-3.365, -3.217,-5.285, -2.097, -1.69, -1.482, -2.304, P<0.05). Treg cells were negatively correlated with disease activity indexes TJC (r=-0.213, P=0.038), VAS (r=-0.299, P=0.003), PHGA (r=-0.287, P=0.005), DLQI (r=-0.208, P=0.043). Th17 cells increased from [6.3 (2.3, 11.5) cells/μl] to [11 (7, 20) cells/μl, Z=-2.808, P=0.005] after low-dose IL-2 treatment, Treg cells increased from [27 (15, 30) cells/μl] to [71 (37, 98) cells/μl, Z=-3.945, P<0.01]. Because the growth rate of Treg was much higher than Th17, Th17/Treg [before IL-2 treatment: 0.26 (0.11, 0.44), after IL-2 treatment: 0.14 (0.1, 0.35)] returned back to the normal range. After the treatment with IL-2, the patient's activity indicators were significantly improved, and there were no reversible adverse reactions. Conclusion The reduction of Treg cells may be involved in the occurrence and devel-opment of PsA. Low-dose IL-2 treatment can effectively promote the proliferation of Treg cells and the recovery of Th17/Treg balance, which is conducive to the improvement of the condition and good safety.
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Objective To investigate the levels of T helper cell 17 (Th17), Th17-related cytokines in-terleukin 17 (IL-17) and interleukin 23 (IL-23) and regulatory T cell (Treg) in relapsing remitting multiple sclerosis (RRMS). Methods In a case-control study, plasma was collected from RRMS patients (n=20) and healthy subjects as control group (n=20). The percentages of Th17 and Treg cells and the levels of IL-17 and IL-23 were tested. The levels of Th17, Treg, IL-17 and IL-23 of the two groups were compared. Patients were treated with methylprednisolone. The levels of Th17, Treg, IL-17 and IL-23 of multiple sclerosis (MS) patients b efore and after treatment were compared. Expanded disability status scale (EDSS) score and the number of Gd-enhancing lesions were evaluated in the case group. Statistical analysis was made by body mass index (IBM) statistical program for social sciences (SPSS) 17.0 software. Independent sample t test was conducted to compare the measurement data of the case group and the healthy control group, and enumeration data were compared by χ2 test; paired sample t test was performed to compare the data of the case group before and after treatment; Pearson correlation analysis was made forthe variables of the MS group before treatment. Results In the RRMS group, the percentage of Th17 cells in peripheral blood was significantly higher than the control group [(2.10±0.45)％vs (1.09±0.20)％](t=9.130, P<0.01), the levels of Th17-related cytokines IL-17 and IL-23 were remarkably higher than the control group (IL-17:t=19.843, P<0.01;IL-23:t=22.747, P<0.01), and the percentage of Treg cells was significantly lower than the control group [(1.33 ±0.30)％vs (2.52±0.30)％], (t=12.422, P<0.01). The levels of Th17 and IL-17 were positively associated with EDSS score (Th17: r=0.458, P<0.05; IL-17: r=0.480, P<0.05), there was no significant-correlation between the level of IL-23 and EDSS score (r=0.368, P>0.05), and Th17, IL-17 and IL-23 were positively correlated with the number of Gd-enhancing lesions (Th17: r=0.446, P<0.05; IL-17: r=0.544, P<0.05; IL-23: r=0.461, P<0.05). The levels of Th17, IL-17 and IL-23 in the RRMS group after the treatment with methylprednisolone were obviously decreased than before treatment (Th17: t=5.747, P<0.01; IL-17: t=9.967, P<0.01; IL-23: t=14.697, P<0.01), while that of Treg was apparently increased (t=10.050, P<0.01). Compared with the control group, the levels of Th17, IL-17 and IL-23 in the RRMS group after treatment were higher (Th17: t=6.889, P<0.01;IL-17:t=7.185, P<0.01;IL-23:t=13.284, P<0.01), and the percentage of Treg was lower (t=7.622, P<0.01). EDSS score of the RRMS group after treatment was remarkably decreased than before treatment(t=6.190, P<0.01), but the number of Gd-enhanced lesions after treatment was no significantiy changed (t=1.453, P>0.05). Conclusion Th17/Treg expression imbalance and Th17-related cytokines IL-17, IL-23 may participate in the pathological process of MS, and they might be therapeutic target for MS.
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Objective To determine the CD4+CD25+Foxp3+T regulatory (Treg) cell levels in peripheral blood (PB) of patients with autoimmune diseases (AID) and age-and sex-matched healthy controls. Methods Clinical data and laboratory examinations of AID cases (n=1561) and healthy controls (n=196) were enrolled. The levels of PB Treg cells, other T lymphocyte subsets [total T, CD4+T, CD8+T, T helper1 (Th1), T helper 2 (Th2), and T helper17(Th17) cells] and clinical indicators, laboratory test results were analyzed retro-spectively. Data were analyzed by t test, Mann-Whitney U test,χ2 test and Spearman correlation analysis. Results ①The absolute counts of Treg [22.9(18.31, 36.47) vs 30.24(21.85, 41.34), Z=-3.974, P<0.01], total T (Z=-4.234, P<0.01), CD8+T (Z=-3.801, P<0.01), Th17 (Z=-3.740, P<0.01) cells in PB of patients with AID were significantly lower than those of healthy controls, the levels of CD4+T/Treg (Z=-3.366, P=0.001), Th1/Treg (Z=-3.213, P=0.001) and Th2/Treg (Z=-2.490, P=0.013) in PB of AID patients were higher than those of healthy controls.② The levels of inflammatory indicators were associated with numbers of T lymphocyte subsets. ③ The levels of Treg (Z=-3.624, P<0.01), total T (Z=-2.954, P=0.009), CD4+T (Z=-3.005, P=0.003), Th2 (Z=-1.896, P=0.049) cells in PB of the patients who had been treated with hormones and/or biological or non-biological disease-modifying anti-rheumatic drugs (DMARDs) were significantly lower while the levels of total T/Treg (Z=-2.460, P=0.014), CD8+T/Treg (Z=-3.197, P=0.001) in PB were higher than those of the primary treatment patients. ④ The levels of Treg (Z=-7.105, P<0.01), total T (Z=-2.954, P<0.01), CD4+T (Z=-6.909, P<0.01), Th1 (Z=-4.875, P<0.01), Th2 (Z=-5.751, P<0.01), Th17 (Z=-5.121, P<0.01) cells in PB of the patients with important organs involvement were lower while the ratios of total T/Treg (Z=-4.500, P<0.01), CD8+T/Treg (Z=-5.925, P<0.01) were higher than those non-organ involvement patients. ⑤ The absolute counts levels of T lymphocyte subsets in the AID patients were not significantly correlated with whether there was a single AID and/or multiple AID overlaps. Conclusion The absolute number of peripheral Treg cells decreases significantly in AID, and is correlated with inflammatory indicators. Patients with retreated and organ involve-ment have fewer Treg cells. Our results suggest that Treg cells may play an important role in the pathogenesis of AID.
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Objective To explore the expression and their significance of peripheral Th17 cells and regulatory T cells (Tregs) in idiopathic inflammatory myopathy,and analyze the relationship between the expression and clinical indicators,imaging and pathological changes.Methods Clinical data,laboratory tests,imaging and pathological changes of IIM cases (n=85) and healthy controls (n=70) were enrolled.Clinical data included the classification,age,gender,course of the disease;laboratory tests including erythrocyte sedimentation rate (ESR),C-reactive protein (CRP),creatine kinase (CK),creatine kinase isoenzyme-MB (CKMB),lactate dehydrogenase (LDH),hydroxybutyrate dehydrogenase (HBDH).The level of peripheral Th17,Treg cells and clinical indicators,laboratory tests,imaging and pathological changes were analyzed retrospectively.Since the data was disregarded from the normal distribution,the median four quantile method was used for statistical description.Two samples were compared with Mann-Whitney U test,and the correlation between variables was Spearman rank correlation analysis.Results ①) The levels of Th17 cells in the case group was not significantly different from that in the control group [6.18(3.42,13.65) cell/μl vs 7.42(5.02,11.13) cell/μl,P＞0.05],the levels of Treg cells in patients was significantly lower than that in the control group [21.25(12.48,35.67) cell/μl vs 36.95(30.37,47.12) cell/μl,P＜0.05],the ratio of Th17/Treg was also significantly higher than that in the control group [0.31(0.21,0.47) vs 0.18(0.14,0.31),P＜0.05].② Peripheral Treg cells levels were not correlated with ESR,CRP,CK-MB,LDH and HBDH (P＞0.05).Peripheral Treg cells levels were negatively correlated with CRP (r=-0.279,P＜0.05),but no correlated with ESR,CK-MB,LDH and HBDH (P＞0.05).③ According to the involvement of important organs,patients were classified into two groups:organ involvement group and non-organ involvement group.The levels of Treg cells in the organ involvement group was fewer than that in non-organ involvement group [16.54(8.84,27.34) cell/ul vs 24.87(14.44,43.37) cell/ul,P＜0.05],and the ratio of Th17/Treg in the organ involvement group was significantly higher than that in non-organ involvement group [0.41(0.29,0.68) vs 0.29(0.19,0.39),P＜0.05].④) Peripheral Th17 cells levels in patients with skeletal muscle inflammatory edema was significantly higher than that of non-inflammatory edema patients [10.70 (4.11,14.51) cell/μl vs 3.10 (1.27,5.15) cell/μl,Z=-2.460,P＜0.05].⑤ The levels of Th17,Treg cells and ratio of Th17/Treg did not correlate with pathological features of inflammatory infiltration (P＞0.05).Conclusion The absolute number of peripheral Treg cells decreases significantly in IIM,and correlates with CRP.Patients with organ involvement have fewer Treg cells,and there is imbalance between Th17 and Treg.When muscle MRI presents with inflammatory edema,patients may have high level of Th17 cells.Our results suggest that Treg cells may play an important role in the pathogenesis of IIM.
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Objective To investigate the effect and mechanism of placental protein 14 on the proliferation and differentiation of B cells.Methods The lymphocyte of human peripheral blood was separated by gradient centrifugation.Flow cytometry was used to detect the proportion of CD4+CXCR5+follicular helper T cells (Tfh cells),CD4+CXCRS+Foxp3+ follicular regulatory T cells (Tfr cells),CD3-CD19+B cells and CD3-CD38+ plasma cells.ELISA method was used to detect the concentration of IL-21,IL-10 and TGF-beta in the supernatant,and the co-culture of cells was performed by Transwell chamber;t test was used for comparison between groups.Results The proportion of Tfh cells and Tfr cells in the control group was (2.52±0.16)％ and (1.26±0.24)％,respectively,and that of the placental protein 14 groups were (0.84±0.09)％ and (4.64±0.68)％,respectively.There was a significant difference between the two groups (t=9.150,P=0.000 8 and t=4.669,P=0.009 5).Pplacental protein 14 could further inhibit the secretion of IL-21 (t=5.086,P=0.007 1),and promote the increase of IL-10 and TGF-β concentration (t=3.599,P=0.022 8 and t=6.651,P=0.002 7).The percentage of B cells and plasma cells in the placental protein 14 group were (4.87±0.20)％ and (5.41±0.54)％,which were significantly different from those in the Tfh cell group (t=4.997,P=0.007 5;t=5.110,P=0.006 9).Conclusion Placental protein 14 can inhibit the proliferation of B cells and differentiate into plasma cells by inhibiting the differentiation of Tfh cells and increasing the proportion of Tfr cells.
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Notch family,a kind of important transmembrane signaling proteins,is highly evolutionarily conserved in the development process of multicellular organisms. Notch signaling pathway can precisely regulate cell development process through the interaction between neighboring cells,such as cell proliferation,differentiation and apoptosis.The regulatory T (Treg)cells and T helper 17(Th17)cells are new types of CD4+T cell subsets.In the physiological state of the organism,they can secrete relevant various kinds of cytokines,and systematically regulate the balance of immune system.In recent years, more and more studies have found that close relationship between Notch signaling pathway and Treg/Th17 cell balance, which is extensively involved in the various diseases. Therefore, this paper briefly reviewed the regulation mechanism of Notch signaling pathway on Treg/Th17 cells in diseases such as hematological diseases and autoimmune diseases.
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Nonalcoholic fatty liver disease (NAFLD) is closely associated with insulin resistance and genetic susceptibility and is one of the chronic liver diseases that threaten human health .Under certain conditions, Th17 cells and regulatory T (Treg) cells can be transformed to each other to maintain immune homeostasis.In recent years, more and more studies have been performed on the involvement of Th 17 and Treg cells in the development and progression of liver diseases .Th17 cells, Treg cells, and their balance may become the new targets for the treatment of NAFLD.This article reviews the latest research advances in the association of Th 17 and Treg cells with NAFLD and the role of Th17/Treg balance in the development and progression of NAFLD .
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Objective To investigate the expression mechanism and significane of helper T cells in children with aplastic anemia(AA).Methods 53 children of AA were divided into heavy AA group(SAA group,21 cases),light AA group(MAA group,i7 cases),AA remission group (CR group,15 cases) by the disease,the other taken the non-aplastic anemia blood platelet disorders caused by reduced or anemia in children (AL group) of 16 cases,20 healthy children were selected as the NC group.The peripheral blood CD4+,CD4+ CD225+,CD4+ CD25+ CD127low,CD4+ IFN-γ(Thl cells),CD4+ IL-4 + (Th2 cells) in each group were detected by flow cytometry.ELISA test was used to detect peripheral blood levels of transforming growth factor-β (TGF-β),interferon-γ (IFN-γ) and interleukin-4 (IL-4).Results The peripheral blood CD4+,CD4+ CD25+,CD4+ CD25+ CD127low,TGF-beta 1 levels in the SAA group were (26.59 ± 4.37) ％,(3.44 ± 0.29) ％,(3.13 ± 1.16) ％,(14.59 ± 3.10) ng/mL,respectively,which in the MAA group were (32.67 ± 3.19) ％,(5.42 ± 0.28) ％,(4.29 ± 1.21) ％,(22.98 ± 3.38) ng/mL,respectively,which in the CR group were (33.13 ±3.24)％,(5.23 ±0.26)％,(4.36 ± 1.33)％,(23.19 ± 3.91) ng/mL,respectively,which in the AL group were (37.98 ± 4.01)％,(6.89 ± 0.28)％,(4.99 ± 1.42)％,(34.46 ± 5.23) ng/mL,respectively,which in the NC group were (38.66 ± 3.41) ％,(7.01 ± 0.38) ％,(5.10 ± 1.52) ％,(35.17 ±5.i4) ng/mL,respectively,the differences among the four groups were statistically significant(F =23.72,25.49,15.24,24.52,all P ＜ 0.05).Peripheral blood Th1,Th2 and Th1/Th2 levels in the SAA group were (13.04 ± 3.01)％,(3.44 ±0.29)％,(1.99 ± 1.17),respectively,which in the MAA group were (11.01 ±2.89)％,(6.28 ±2.99)％,(1.75 ± 0.97),respectively,which in the CR group were (10.38 ± 3.27)％,(6.41 ± 3.18)％,(1.62 ±1.03),respectively,which in the AL group were (8.033 ±.42) ％,(6.35 ± 3.08) ％,(1.26 ± 1.11),respectively,which in the NC group were (8.41 ± 3.84) ％,(6.23 ± 3.44) ％,(1.34 ± 1.12),the differences among the four groups were statistically significant (F =35.92,42.43,22.24,all P ＜ 0.05).Peripheral blood IFN-gamma and IL-4levels in SAA group were (13.04 ± 2.58) pg/mL,(17.22 ± 3.88) pg/mL,respectively,which in MAA group were (10.11 ± 2.22) pg/mL,(17.24 ± 4.21) pg/mL,respectively,which in the CR group were (9.88 ± 2.16) pg/mL,(17.01 ±4.00)pg/mL,respectively,which in the AL group were (8.01 ± 1.68)pg/mL,(16.63 ± 3.58)pg/mL,respectively,which in the NC group were (38.66 ± 3.41) pg/mL,(16.743 ±.81) pg/mL,the differences among the four groups were statistically significant (F =24.17,3.39,all P ＜ 0.05).Conclusion Treg cells decreased,the inhibition extent of TGF-β1 on Th1 cells and IFN-γsecretion decreased,which leading to Th1/Th2 shifted to Th1,leading to hematopoietic marrow failure may be one of the pathogenesis of children sufferred from AA.
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T follicular helper cells(Tfh)possess the function to induce efficient B cell maturation in germinal center (GC).However,HIV infection can destroy the structure of lymphoid follicles,and disturb the quantity and function of Tfh,resulting in the dysfunction of B cells.Meanwhile,HIV may remain dormant in the Tfh after invading host and escape the elimination of immunologic system.Consequently,the Tfh turns into the sanctuary of HIV.By the above mentioned mechanism,HIV infection leads to the progressive damage of CD4 + T lymphocytes, hypergammaglobulinemia and the loss of memory B lymphocytes.
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Objective To observe the effect of complex sophorae injection combined with FOLFOX4 on Th17 cells, IL-17 and survival rate in patients with rectal cancer.Methods A total of 128 patients with rectal cancer were sellected in this study. The patients were divided into the control group (n=64) and observation group (n=64). The control group received the treatment of FOLFOX4 regimen, and the observation group received the treatment of FOLFOX4 regimen and sophorae injection. The Th17 cells were detected by flow cytometry, and IL-17 by ELISA assay.Results After treatment, the Th17 cells (11.28% ± 2.42%vs. 13.12% ± 3.15%,t=2.376) and IL-17 (16.58 ± 3.26 ng/mlvs. 21.84 ± 4.12 ng/ml,t=2.391) in observation group was lower than those in control group (P<0.05). After treatment, the effective rate (60.9%vs. 43.8%,χ2=2.384) and control rate (92.2%vs. 81.3%,χ2=2.371) in observation group was higher than that in control group (P<0.05). The different levels of white blood cells (37.5%vs. 60.9%,χ2=2.417), anemia (35.9%vs. 59.3%,χ2=2.421), thrombocytopenia (34.4%vs. 62.5%,χ2=2.432), nervous system toxicity (15.6%vs. 37.5%,χ2=2.458), gastrointestinal tract reaction (21.9%vs. 43.8%,χ2=2.453), oral mucositis incidence (28.1%vs. 57.8%,χ2=2.451) in observation group were lower than those in control group (P<0.05). The 1 year survival rate was 79.7% (51/64) in observation group,, which was higher than that of 60.9% (39/64) in control group (χ2=2.414,P<0.05).Conclusions The complex sophorae injection combined with FOLFOX4 regimen can reduce Th17 cells and IL-17 in patients with rectal cancer, improve survival rate, and reduce the clinical toxicity of chemotherapy drugs.
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ObjectiveTo investigate the role of T helper (Th) 22 and Th17 cells in the pathogenesis of severe preeclampsia.MethodsThirty women with severe preeclampsia who delivered in the Third Affiliated Hospital of Zhengzhou University from October 2014 to February 2016 were enrolled in the study. Thirty healthy pregnant women matched for age and gestational weeks were recruited as the control group. The frequencies of Th22 and Th17 cells in peripheral whole blood were determined by flow cytometry. The concentrations of interleukin (IL)-22 and IL-17A in plasma were detected by enzyme-linked immunosorbent assay. Independent two samplest-test, non-parametric test and Spearman correlation analysis were used for statistical analysis.ResultsThe percentage of Th22 and Th17 cells in the severe preeclampsia group were significantly higher than those in the control group, respectively[Th22 cells: 0.59% (0.39%-1.13%) vs 0.40%(0.23%-0.57%),Z=2.530,P=0.010; Th17 cells: 3.24% (3.02%-3.97%) vs 1.87% (1.53%-2.64%),Z=5.046, P=0.000]. So were the plasma levels of IL-22 and IL-17A[IL-22: 285.72 (247.63-306.69) vs 233.85 (184.92-258.38) pg/ml,Z=4.341,P=0.001; IL-17A: 27.53 (23.84-32.78) vs 17.36 (15.58-19.13) pg/ml,Z=4.924, P=0.000]. There was a positive correlation between circulating Th22 and Th17 cells in the severe preeclampsia group (r=0.534,P=0.015), while no correlation was found in the control group (r=0.345,P=0.136). Positive correlation was found in plasma level of IL-22 with Th22 cells (r=0.600,P=0.005), but not with Th17 cells (r=0.398,P=0.082) in the severe preeclampsia group.ConclusionsIncreased Th22 cells and high IL-22 concentrations in the peripheral blood of severe preeclampsia patients may indicate a self-defense mechanism in the maternal body. Th22 cells and Th17 cells may interact with each other.
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Objective To explore the changes of Tr cells and IL-17 levels in peripheral blood of patients with antiphospholipid syndrome (APS) and the clinical significance.Methods The quantity of the CD4+ CD25+ Tr cells and proportion of CD4+ CD25+ Tr cells/CD4+ T cells were detected by flow cytomety,and the levels of IL-17 were detected by ELISA in 60 cases with APS(APS group) and 60 healthy people(control group).Results The levels of Tr,Tr/CD4+,Foxp + 3 Tr/Tr in the APS group were (3.03 ± 0.40) ％,(0.11 ± 0.02),(0.40 ± 0.10),respectively,which in the control group were (5.76 ± 0.84)％,(0.15 ± 0.03),(0.73 ± 0.15),respectively,the differences were statistically significant(t =22.73,8.59,14.18,all P ＜ 0.01).The levels of serum IL-17 and IL-17/Tr cells in APS group were (15.31 ±2.00)pg/mL,(5.05 ±0.29)pg/mL,respectively,which in the control group were (6.63 ± 1.52) pg/mL,(1.15 ± 0.14) pg/mL,respectively,there were statistically significant differences (t =29.17,93.81,all P ＜0.05).The levels of serum IL-17 was negatively correlated with Tr cells level in peripheral blood of patients with APS(r =-0.801,P ＜0.01).Conclusion There is peripheral blood cellular immune function disorder in APS patients,the number and active changes of CD4+ CD25+ Tr cells and IL-17/Tr ratio imbalance may play a role in the pathogenesis of APS.
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Objective To investigate the effect and mechanism of adenovirus vector mediated SOCS 3 gene transfection in CD4+ Th cell differentiation and expression of inflammatory cytokines of mouse .Methods The CD4+ Th cells were isolated from spleen of C57bl/6 mouse and cultured .Ad‐SOCS3 were transfected into the CD4+ Th cells .PHA was used for culturing with the CD4+ Th cells .RT‐PCR were used to detect the mRNA expression ,and Western blot were used to detect the protein expression of cytokines .Results Compared with the control group ,the gene and protein expression of T‐bet ,IL‐2 ,IFN‐γ,STAT4 and IL‐12Rβ2 in the transfected group were significantly down‐regulated ,the gene and protein expression of SOCS3 ,GATA‐3 ,IL‐4 ,IL‐6 ,IL‐10 and STAT6 were significantly up‐regulated(P<0 .01) .Conclusion The results indicate that SOCS3 gene transfection can up‐regu‐late SOCS3 mRNA and protein expression in the CD4+ Th cells ,down‐regulate the JAK/STAT pathway ,inhibition of Th1 cell dif‐ferentiation ,and down regulation of inflammatory cytokine gene and protein expression ,and indirectly promote Th2 cell differentia‐tion ,and up the corresponding inflammatory cytokine gene and protein expression .
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Objective To investigate the imbalance of Th1/Th2 cell response in patients with systemic lupus erythematosus (SLE) combined with coronary heart disease .Methods SLE patients ,SLE patients with coronary heart disease and healthy con-trols were enrolled and blood samples were collected .T-bet/GATA-3 ,the transcription factors of Th1/Th2 cells ,were detected by real-time PCR ;the intracellular cytokines IFN-γ and IL-4 in CD4 + T cells were stained by fluorescent antibodies and detected by flow cytometry ;the level of serum IFN-γ and IL-4 were detected by ELISA .Results Comparing with healthy control group ,the ex-pression level of Th1 transcription factor T-bet ,the introcellular secretion of IFN-γ in CD4 + T cells and the serum IFN-γ were all decreased in non-coronary heart disease patients with SLE( P < 0 .05) .Comparing with non-coronary heart disease patients with SLE or healthy control group ,the expression level of Th1 transcription factor T-bet ,the introcellular secretion of IFN-γ in CD4 + T cells and the serum IFN-γ were all increased in patients with SLE combined coronary heart disease(P< 0 .05) ;while the expression level of Th2 transcription factor GATA-3 ,the introcellular secretion of IL-4 in CD4 + T cells and the serum IL-4 were all decreased in patients with SLE combined coronary heart disease(P< 0 .05) .Conclusion There were imbalance towards Th1 cell response in patients with SLE combined coronary heart disease ,which may related to the occurrence and development of disease .
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Objective To investigate whether the proportions of Th17/Treg balance were impaired in the peripheral blood of patients in different phases of synovitis acne pustulosis hyperostosis osteitis (SAPHO) syndrome.Methods We studied 22 cases diagnosed as SAPHO syndrome and 11 healthy controls.According to the scores of VAS pain,BASDAI and BASFA,the 22 patients were divided into active group and stable group.By means of flow-cytometry,the frequencies of total and different subsets of Th17 and Treg cells in peripheral blood mononuclear cell of different groups of SAPHO syndrome and healthy controls were studied.The values of Th17/Treg balance were analyzed.The relationship was analyzed with Kruskal-Wallis test,Mann-Whitney test and Pearman's test.Results The mean percentage of Th17 cells was markedly higher in the active group [(2.74±0.25)％] than in the stable group [(1.16±0.09)％] (U=0.000,P＜0.01) and healthy controls [(1.13±0.11)％] (U=0.000,P＜0.01).No differences were found among active group [(2.10±0.20)％],stable group [(2.51±0.20)％] and control group [(2.44±0.22)％] (x2=2.16,P=0.339 4).The ratio of Th17 cells to Treg cells was markedly higher in active group [(1.48±0.25)％] than in the other two groups [(0.47±0.03)％] (U=0.000,P＜0.01).We also found the positive correlation of the ratios of Th17/Treg cells with the values of VAS in SAPHO syndrome patients (r=0.752 7,P＜0.01).Conclusion The results demonstrate that the development of SAPHO syndrome is closely related to the imbalance of systemic Th17/Treg cells,Increased ratio of Th17/Treg cells may be the main factor that cause disease recurrence,and then,lead to the manifestations of high levels of inflammation and joint pain.