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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 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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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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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.
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Objective To evaluate therapeutic effects of metformin on the expression of serum cytokines,balance of splenic Th17/regulatory T cells (Treg) and expression of splenic AMPK-mTOR in collagen-induced arthritis (CIA) rats,and the mechanism thereof.Methods The rat model of CIA was established by injecting bovine type Ⅱ collagen.Forty rats were randomly divided into five groups:the CIA model group(sterile water by gavage),Met-30 mg/kg group (metformin 30 mg ·kg-1 ·d-1 by gavage),Met100 mg/kg group(metformin 100 mg ·kg-1 ·d-1 by gavage),Met-300 mg/kg group(metformin 300 mg ·kg-1 ·d-1 by gavage) and control group (sterile water by gavage).The hind paw volume was recorded once a week.The serum level of cytokines,tumor necrosis factor (TNF)-α,interleukin (IL)-1β,IL-6,and IL-17,were measured by enzyme linked immunosorbent assay (ELISA) 35 days after the initial immunization.The quantity of Th17 and Treg cells were examined by flow cytometry.The expression of AMPK,p-AMPK,mTOR and p-mTOR were examined by western blotting.One-way analysis of variance was used to evaluate the experimental data.Results The values of hind paw volume were decreased on the 35 d of the initial immunization in the Met100 mg/kg [(2.43±0.37) ml,t=2.97,P＜0.05] and Met-300 mg/kg groups [(2.58±0.21) ml,t=2.96,P＜0.05] than those of CIA model group (2.97±0.23) ml.The serum levels of TNF-α,IL-1β,IL-6 and IL-17 on the 35-d after the initial immunization were significantly lower in the metformin therapeutic groups [Met-300 mg/kg group TNF-α (104±8) pg/ml,t=42.77,P＜0.05;IL-1β (183±24) pg/ml,t=60.457,P＜0.05;IL-6 (19.3±2.8) pg/ml,t=53.62,P＜0.05;IL-17 (64.5±6.7) pg/ml,t=47.92,P＜0.05] than those of the CIA model group [TNF-α (246±8) pg/ml;IL-1β (1 336±40) pg/ml;IL-6 (87.0±5.1) pg/ml;IL-17 (282.3±6.8) pg/ml].The quantity of Th17 and Treg cells were significantly different in the Met-300 mg/kg group than those of the CIA model group 35 d after the initial immunization [Th17(6.57±0.39) vs (9.89±0.53),t=8.74,P＜0.05;Treg (7.60±0.45) vs (3.94±0.61),t =8.37,P＜0.05].The expression of p-AMPK on the 35 d after the initial immunization in the metformin therapeutic groups was significantly higher than in the CIA model group(P＜0.05),and the expression of p-mTOR was significantly lower (P＜0.05).Conclusion Metformin can significantly inhibit the serum levels of TNF-α,IL-1β,IL-6 and IL-17 in CIA model rats,and regulate the balance of Th17/Treg through AMPK-mTOR signaling pathway.
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Regulatory T cells are a subset of T cells, and can inhibit the body′s immune response and induce immune tolerance, which has become one of the hot topics in the field of immunological research in recent years. Regulatory T cell dysfunction and the change in the number of regulatory T cells are closely associated with the progression and treatment of autoimmune diseases, infectious diseases, tumor immune tolerance, transplant rejection, and allergic diseases. This article summarizes the surface markers and immunological mechanism of regulatory T cells, as well as the association of regulatory T cells with the pathogenesis of hepatitis B and antiviral therapy.
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In recent years, the role of immune cells in hepatitis B virus (HBV)-related liver diseases has attracted more and more attention. This article reviews the roles of regulatory T cells (Treg) and T-helper cell type 17 (Th17) in the development, progression, and prognosis of HBV-related liver diseases, especially HBV-related liver fibrosis and liver failure, as well as hepatocellular carcinoma. It is pointed out that the dynamic changes of Treg and Th17 cells in different stages of HBV infection and their roles in hepatocellular carcinoma need further investigation, and future studies on the regulatory effects of various signaling pathways on Treg or Th17 cells are needed to provide a more precise direction for the treatment of HBV-related diseases.
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Objective To evaluate effects of a fusion protein LTβR-Fc, which can block the herpesvirus entry mediator ligand (LIGHT-HVEM)signaling pathway, on ovalbumin-induced dermatitis in a mouse model. Methods Thirty BALB/c mice were randomly and equally divided into 3 groups: blank control group treated with 100 μl of sodium chloride physiological solution, model group sensitized with 100 μl of sodium chloride physiological solution containing 100 μg ovalbumin, blocker group firstly blocked with 100 μl of sodium chloride physiological solution containing 100 μg LTβR-Fc followed by sensitization with 100 μl of sodium chloride physiological solution containing 100 μg ovalbumin at 24 hours after the blocking. Disease severity was evaluated by eczema area and severity index (EASI)score, and lesional size was measured on day 0, 4, 8, 12, 15, 20, 23, 27, 31 and 34 after the first sensitization. A total of three sessions of sensitization were carried out. At the end of treatment, all the mice were sacrificed after serum was obtained from their orbital cavities. Thereafter, tissue specimens were obtained from skin lesions, and single cell suspensions of the spleen were prepared. RT-PCR was performed to detect mRNA expressions of interferon γ (IFN-γ), interleukin 4 (IL-4)and IL-5 in murine lesions, ELISA to measure IFN-γ, IL-4 and IL-5 levels in culture supernatants of murine splenocytes, as well as ovalbumin-specific and total IgE and IgG1 levels in murine sera. Results LTβR-Fc significantly suppressed inflammatory response in the mouse model of dermatitis induced by ovalbumin. Compared with the model group, the blocker group showed significantly decreased lesion area and EASI score (both P < 0.05). In addition, a significant decrease was observed in the mRNA expressions of IL-4 (0.88 ± 0.25 vs. 1.81 ± 0.25, P < 0.05), IL-5 (0.75 ± 0.15 vs. 1.24 ± 0.26, P < 0.05)and IFN-γ (0.62 ± 0.09 vs. 1.11 ± 0.19, P < 0.05)in murine lesions, and in supernatant levels of IL-4 (9.58 ± 1.44 ng/L vs. 20.12 ± 5.39 ng/L, P < 0.05), IL-5 (11.37 ± 2.02 ng/L vs. 22.77 ± 4.07 ng/L, P < 0.05)and IFN-γ (16 167 ± 950.40 ng/L vs. 23 930 ± 44.20 ng/L, P < 0.05)in the blocker group compared with the model group. The serum levels of both total IgE and ovalbumin-specific IgE were significantly lower in the blocker group than in the model group(total IgE: 27 466.67 ± 2 052.64 μg/L vs. 32 277 ± 407.53 μg/L, P < 0.05; ovalbumin-specific IgE: 1 296.33 ± 32.72 μg/L vs. 2 323.33 ± 502.43 μg/L, P < 0.05), so were those of total IgG1 (0.46 ± 0.11 μg/L vs. 0.84 ± 0.11 μg/L, P < 0.05)and ovalbumin-specific IgG1 (0.62 ± 0.11 μg/L vs. 0.86 ± 0.07 μg/L, P < 0.05). Conclusion The fusion protein LTβR-Fc can alleviate symptoms of ovalbumin-induced dermatitis in the mouse model likely by suppressing the LIGHT-HVEM signaling pathway, suggesting that this signaling pathway may serve as a target for the treatment of dermatitis(such as atopic dermatitis).
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Objective To investigate the relationship between peripheral blood circulating follicular helper T cells and antibody-secreting B cells in patients with ankylosing spondylitis (AS). The role of circulating follicular helper T cells and antibody-secreting B cells in the pathogenesis of AS were explored. Methods Flow cytometry was used to detect the levels of peripheral blood CD4 +CXCR5+ T (cTfh), CD4+CXCR5+PD-1+ T, CD4+CXCR5+ICOS+ T, CD19+ B, CD19+CD38+ B cells in 59 patients with AS (including 36 cases of active AS patients and 23 cases of inactive AS patients). In addition, twenty healthy persons were selected as the controls. Data analysis were performed by independent-sample t test, One way ANOVA analysis, Pearson's and Spearman's correlation test. Results The percentages of cTfh [(26.8 ±10.4)%], CD4+CXCR5+PD-1+T [(12.1±14.0)%], CD4+CXCR5+ICOS+T [(13.6±9.5)%], CD19+CD38+B [(80.7±13.0)%] in the peripheral blood of AS group were significantly higher than healthy controls [(15.6 ±4.5)%, (6.4 ±2.4)%, (9.4 ± 4.5)%, (68.2±13.0)%] (t=6.663, P<0.01; t=2.999, P<0.01; t=2.573, P<0.05; t=2.712, P<0.01). The percentages of cTfh in the active AS group [(30.2 ±11.0)%] were significantly higher than those in the inactive AS group [(21.4±6.5)%] and HC (t=3.444, P<0.01;t=7.004, P<0.01). The percentage of CD19+CD38+B[(85.1±10.0)%] in the peripheral blood of active AS group was significantly higher than that of the inactive AS group [(73.8 ±14.2)%] and HC (t=3.561, P<0.01;t=5.410, P<0.01). The relationship between Bath AS disease activity index (BASDAI) and the percentage of cTfh, CD19+CD38+B was a positive correlation (r=0.442, P<0.01; r=0.405, P=0.001), and significant positive correlation was observed between the percentages of cTfh and CD19+CD38+B cells (r=0.420, P=0.001). Conclusion CD4+CXCR5+cTfh cells are significantly increased in peripheral blood in AS patients with aberrant CD19+CD38+ antibody-secreting B cells, suggesting that cTfh and CD19+CD38+antibody-secreting B cells may play an important role in the pathogenesis of AS .
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OBJECTIVETo observe the change of peripheral blood Th17 cells in patients with different kinds of CRSwNPs and the relationship between the frequency of Th17 cells and inflammatory cell density in nasal polyps tissue, and to explore the correlation between levels of peripheral blood Th17 cells and prognosis of patients with CRSwNPs.METHODSEighty one patients with CRSwNPs and 20 controls were recruited in this research. Flow cytometer was used to detect the expression of peripheral blood Th17 cells. The number per 10000μm2 of infiltrated inflammatory cells in nasal polyp tissue (including eosinophils, neutrophils, lymphocytes and plasma cells) was counted at a high-power field. The CT scores were evaluated by Lund-Mackay system and the nasal endoscopy scores were graded according to Lund-Mackay methods. RESULTSThe percentages of Th17 cells in patients with E-CRSwNPs and NE-CRSwNPs were 2.10% (3.75%, 1.40%)和1.10% (1.70%, 0.73%). There was significant difference between the two groups (Mann-WhitneyU=358.0,Z=-2.965, P=0.001). Furthermore, a positive association between the percentage of Th17 cells in peripheral blood and the eosinophil density of nasal polyp (r=0.408,P<0.001) was demonstrated. The percentage of Th17 cell in peripheral blood was significantly correlated with the endoscopic score of CRSwNPs at third month after the operation (r=0.458, P<0.001).CONCLUSIONThl7 might be involved in the pathogenesis and prognosisof eosinophilic CRSwNPs.
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Objective To compare the differences of cytokines IFN‐γ,IL‐2 ,IL‐4 ,IL‐6 ,IL‐10 ,IL‐13 and IL‐17 expression lev‐els mainly secreted by peripheral blood Th1 ,Th2 and Th17 cells and to investigate the correlation between the cytokines in the Han and Uyghur cervical cancer patients with the clinical stage and tumor differentiation degree .Methods The blood samples in 66 ca‐ses of pathologically diagnosed cervical cancer (Han in 22 cases ,Uyghur in 44 cases) before treatment in our hospital were collect‐ed .The concentrations of IFN‐γ,IL‐2 ,IL‐4 ,IL‐6 ,IL‐10 ,IL‐13 and IL‐17 were measured by using Luminex assay ,then the differ‐ences of cytokines were compared between Han and Uyghur patients;according to the clinical stage and tumor differentiation de‐gree ,the grouping was performed ,then the differences of cytokines in different subgroups were compared between Han and Uyghur cervical cancer patients .Results The levels of IFN‐γ,IL‐2 ,IL‐4 ,IL‐6 ,IL‐10 ,IL‐13 and IL‐17 in the Uyghur cervical cancer group were higher than those in the Han cervical cancer group(P<0 .05);the levels of IL‐2 ,IL‐4 and IL‐10 secreted by Th cells in the stage Ⅰ - Ⅱ Uyghur cervical cancer group were higher than those in the stage Ⅰ - Ⅱ Han cervical cancer group(P<0 .05);the levels of IFN‐γ ,IL‐2 ,IL‐4 ,IL‐6 ,IL‐10 ,IL‐13 and IL‐17secreted by Th cells in the stage Ⅲ - Ⅳ Uyghur cervical cancer group were higher than those in the stage Ⅲ - Ⅳ Han cervical cancer group(P<0 .05);the levels of IFN‐γ,IL‐2 ,IL‐4 ,IL‐6 ,IL‐10 ,IL‐13 and IL‐17 secreted by Th cells in middle to high differentiation Uyghur cervical cancer group were higher than those in middle to high differentiation Han cervical cancer group(P<0 .05) .Conclusion In the HPV16‐positive cervical cancer patients ,the concentrations of cytokines secreted by Th cells are different between Uyghur group and Han group ,these differences are more significant in the stage Ⅲ - Ⅳ cervical cancer and in middle to high differentiated cervical cancer .