Relationship between Th17 immune response and cancer

Cancer is the second leading cause of death worldwide and epidemiological projections predict growing cancer mortality rates in the next decades.Cancer has a close relationship with the immune system and,although Th17 cells are known to play roles in the immune response against microorganisms and in autoimmunity,studies have emphasized their roles in cancer pathogenesis.The Th17 immune response profile is involved in several types of cancer including urogenital,respiratory,gastrointestinal,and skin cancers.This type of immune response exerts pro and antitumor functions through several mechanisms,depending on the context of each tumor,including the protumor angiogenesis and exhaustion of T cells and the antitumor recruitment of T cells and neutrophils to the tumor microenvironment.Among other factors,the paradoxical behavior of Th17 cells in this setting has been attributed to its plasticity potential,which makes possible their conversion into other types of T cells such as Th17/Treg and Th17/Th1 cells.Interleukin(IL)-17 stands out among Th17-related cytokines since it modulates pathways and interacts with other cell profiles in the tumor microenvironment,which allow Th17 cells to prevail in tumors.Moreover,the IL-17 is able to mediate pro and antitumor processes that influence the development and progression of various cancers,being associated with variable clinical outcomes.The understanding of the relationship between the Th17 immune response and cancer as well as the singularities of carcinogenic processes in each type of tumor is crucial for the identification of new therapeutic targets.

Correlation of serum nutrient levels with immune cell differentiation and inflammatory response activation in children with pneumonia

Objective:To investigate the correlation of serum nutrient levels with immune cell differentiation and inflammatory response activation in children with pneumonia.Methods:200 children with pneumonia who were treated in our hospital between April 2015 and August 2017 were selected as the pneumonia group, and 100 healthy children who were vaccinated in this hospital during the same period were selected as the normal control group. The differences in serum levels of nutrients, Th1/Th2 cytokines, Th17/Treg cytokines and inflammatory mediators were compared between the two groups. Pearson test was used to assess the relationship between serum nutrient levels and disease severity.Results: Serum Vit A, Fe and Zn levels of pneumonia group were lower than those of control group. The differences in serum Vit D, Ca and Mg levels were not statistically significant between the two groups of children. Serum Th1 cytokines IL-2 and TNF-β contents of pneumonia group were lower than those of control group whereas Th2 cytokines IL-4 and IL-5 contents were higher than those of control group;Th17 cytokines IL-17, IL-21 and IL-22 contents were higher than those of control group whereas Treg cytokines IL-10 and TGF-β contents were lower than those of control group;inflammatory mediators CRP, PCT and MCP-1 contents were significantly higher than those of control group. Pearson test showed that serum nutrients Vit A, Fe and Zn levels in children with pneumonia were directly correlated with the degree of immune cell differentiation and inflammatory response.Conclusion: Serum Vit A, Fe, Zn and other nutrient levels abnormally decrease in children with pneumonia, and the specific level are directly correlated with the severity of the disease.

Correlation between Treg/Th17 imbalance and the liver injury caused by systemic inflammatory response and oxidative stress in children with sepsis

Objective: To study the correlation between Treg/Th17 imbalance and the liver injury caused by systemic inflammatory response and oxidative stress in children with sepsis. Methods:A total of 43 children who were diagnosed with sepsis in Shanghai Jiading District Central Hospital between February 2016 and March 2017were selected as the sepsis group of the study, and children who received physical examination in Outpatient Clinic of Shanghai Jiading District Central Hospital during the same period were selected as the control group of the study. The peripheral blood was collected to determine the contents of Treg and Th17 as well as the expression of oxidative stress molecules, and serum was collected to determine the contents of inflammatory reaction molecules, oxidative stress molecules and liver injury indexes. Results: Peripheral blood Treg and Th17 contents as well as Treg/Th17 of sepsis group were significantly higher than those of control group;serum ALT, AST, TBIL, γ-GT, MIF, sTREM-1, sVCAM-1 and PCT contents as well as peripheral blood MPO and Nrf-2 mRNA expression of sepsis group were significantly higher than those of control group and positively correlated with peripheral blood Treg/Th17 while peripheral blood Keap-1 mRNA expression as well as serum SOD and GSH contents was significantly lower than that of control group and negatively correlated with peripheral blood Treg/Th17. Conclusion: The increase of Treg/Th17 in peripheral blood of children with sepsis is closely related to the activation of inflammatory response and oxidative stress response and the injury of liver function.

Correlation of serum YKL-40 content with eosinophil function as well as Th1/Th2 and Treg/Th17 immunity in patients with allergic rhinitis

Objective: To discuss the correlation of serum YKL-40 content with eosinophil function as well as Th1/Th2 and Treg/Th17 immunity in patients with allergic rhinitis. Methods: A total of 310 patients with allergic rhinitis who were treated in the hospital between January 2015 and May 2017 were selected as allergic rhinitis group and 100 healthy volunteers who received physical examination in the hospital during the same period were selected as normal control group. The differences in serum YKL-40 content, eosinophil function as well as Th1/Th2 and Treg/Th17 cytokine contents were compared between the two groups. Pearson test was used to assess the correlation between serum YKL-40 content and disease severity in patients with allergic rhinitis. Results: Serum YKL-40 content of allergic rhinitis group was higher than that of normal control group;serum eosinophil function IgE and Eotaxin-2 contents of allergic rhinitis group were higher than those of normal control group;serum Th1 cytokines IFN-γand IL-12 contents were lower than those of normal control group while Th2 cytokines IL-4 and IL-13 contents were higher than those of normal control group;serum Treg cytokine TGF-β content was lower than that of normal control group while Th17 cytokine IL-17 content was higher than that of normal control group. Pearson test showed that serum YKL-40 content in patients with allergic rhinitis was directly correlated with the eosinophil function as well as Th1/Th2 and Treg/Th17 immunity. Conclusion: Serum YKL-40 content is abnormally high in patients with allergic rhinitis, and the specific expression is positively correlated with the disease severity.

早期腹腔灌洗对重症急性胰腺炎患者外周血中Th17／Treg细胞平衡的影响

目的探讨早期腹腔灌洗对重症急性胰腺炎（SAP）患者的临床疗效及对外周血辅助性T细胞17（Th1T）／调节性T细胞（Treg）平衡的影响，旨在为SAP的临床治疗提供参考。方法选择SAP患者132例，随机分为A组和B组，每组各66例；另于同期匹配性选取健康志愿者60例，设为对照组。A组早期采用综合治疗措施，B组在此基础上予以腹腔置管灌洗引流术。检测对照组体检当日及A、B组入院第l、4、7天外周血Th17、Treg细胞比例，计算Th17Treg比值；比较A、B组人院第1、4、7天血淀粉酶、C反应蛋白（CRP）水平、APACHEⅡ评分。记录A、B组72h内发生全身炎症反应综合征（SIRS）例数并记录SIRS持续时间、多器官功能障碍综合征（MODs）例数。结果A、B组入院第1天外周血Th17、Treg细胞百分比及Th17／Treg比值均高于对照组体检当日各指标水平（t=3．92—7．39，P〈0．05或P〈0．01）。治疗后，除B组第7天Treg百分比、Th17／Treg比值外，A、B组外周血Th17、Th17／Treg比值及APACHEⅡ评分、血淀粉酶、CRP水平均依次降低（t=3．40—7．17，P〈0．05或P〈0．01），而Treg细胞百分比升高（t=3．56～6．25，P〈0．05或P〈0．01），且B组外周血Th17、Treg细胞百分比及Th17／Treg比值及APACHEⅡ评分、血淀粉酶、CRP水平均低于A组（t=3．55—7．02，P〈0．05或P〈0．01）。B组72h内SIRS、MODS发生率均低于A组（r=4．13、4．59，P〈0．05），B组SIRS持续时间及住院时间均少于A组（t=5．45、4．29，P〈0．05）。Spearman相关分析显示，SAP患者外周血Th17／Treg比值与CRP水平呈显著正相关（r=0.785，P〈0。05）。结论早期腹腔灌洗通过清除腹腔内的炎性介质，减轻SAP患者的早期急性炎症反应，促进Th17／Treg细胞平衡的恢复，阻断或降低SIRS的发展，降低MODS的发生率，减少住院时间，对SAP的临床治疗具有一定的指导和借鉴意义。

急性冠脉综合征患者Th/Tregs水平的变化及其临床意义

目的研究白介素17(IL-17)、白介素35(IL-35)在急性冠脉综合征(ACS)患者外周血中的表达,探讨该指标与肌钙蛋白I(c Tn I)、B型钠尿肽(BNP)及左室射血分数(LVEF)等是否存在相关性。方法选取2016年7月至2017年9月在广州中医药大学第一附属医院住院的ACS患者143例,其中ST段抬高型急性心肌梗死(STEMI)37例,非ST段抬高型急性心肌梗死(NSTEMI)45例,不稳定心绞痛61例;同期体检健康者30例为对照组。以ELISA法检测血清IL-17、IL-35水平,超声心动图Simpson法测定LVEF值。指标间相关性采用Pearson相关分析。结果 STEMI组患者的IL-35、IL-17水平[40.71±14.96)pg/m L、(45.72±13.75)pg/m L]与UAP组[(79.84±21.41)pg/m L、(15.64±9.83)pg/m L]比较差异均有统计学意义(P<0.05),而STEMI与NSTEMI组患者的IL-35水平[(45.96±17.52)pg/m L]和IL-17水平[(39.13±10.94)pg/m L]比较差异均无统计学意义(P>0.05);ACS患者IL-17水平与c Tn I、BNP及D-Dimer呈负相关(r=-0.652,-0.571,-0.484,P<0.05),与LVEF呈正相关(r=0.436,P<0.05);IL-35水平与c Tn I、BNP及D-Dimer呈正相关(r=0.573,0.416,0.597,P<0.05),与LVEF呈负相关(r=-0.391,P<0.05)。结论 ACS患者外周血IL-17、IL-35水平在一定程度上能反映ACS的病情严重程度,可作为冠心病急性心血管事件的独立预测指标。

调节性T细胞抑制约氏疟原虫感染小鼠早期Th1应答的建立

目的探讨调节性T细胞(Tregs)参与约氏疟原虫感染早期调控Th1型免疫应答的相关机制。方法用约氏疟原虫(致死型)感染对照组和anti-CD25 mAb注射组BALB/c小鼠,计数红细胞感染率;感染后第0、3和5d制备脾细胞悬液,磁珠分选、纯化树突状细胞(DCs)并体外培养;ELISA方法检测脾细胞培养上清中IFN-γ和DCs培养上清中IL-12的水平,Griess方法检测脾细胞培养上清中NO含量。结果两组小鼠脾细胞培养上清中IFN-γ和NO水平在感染后第3～5d均明显升高,但对照组小鼠IFN-γ和NO水平明显低于anti-CD25 mAb注射组小鼠。anti-CD25 mAb注射组小鼠DCs培养上清中IL-12的水平于感染后第3d达峰值,并于感染后第5d仍维持较高水平。相比,对照组小鼠DCs培养上清中IL-12的水平仅于感染后第3d出现有意义的升高。结论Tregs在致死型约氏疟原虫感染BALB/c小鼠早期可能通过抑制DCs分泌细胞因子IL-12来抑制Th1型免疫应答的有效建立。

Efficacy of budesonide/formoterol inhalation powder in treating viral pneumonia in children

BACKGROUND Respiratory viruses are increasingly detected in children with communityacquired pneumonia.Further strategies to limit antibiotic use in children with viral pneumonia are warranted.AIM To explore clinical efficacy of budesonide/formoterol inhalation powder for viral pneumonia in children and its impact on cellular immunity and inflammatory factor production.METHODS A total of 60 children with viral pneumonia were recruited:30 receiving budesonide/formoterol inhalation powder and 30 conventional symptomatic treatment.Outcome measures included peripheral blood levels of inflammatory cytokines,CD4^(+),CD8^(+),Th1,Th2,Th17 and Treg,clinical efficacy,and incidence of adverse reactions.RESULTS Compared with the control group,the observation group showed a significant reduction in interleukin-6 and high-sensitivity C-reactive protein levels after treatment.Compared with the control group,the observation group showed a significant increase in CD4^(+)/CD8^(+)and Th1/Th2 levels,and a decrease in Th17/Treg levels after treatment.The total effective rates in the observation group and the control group were 93.75%and 85.00%,respectively,which was a significant difference(P=0.003).CONCLUSION Budesonide/formoterol inhalation powder significantly improved therapeutic efficacy for viral pneumonia in children.The mechanism of action may be related to downregulation of the inflammatory response and improved cellular immune function.

Changes in circulating Foxp3^+ regulatory T cells and interleukin-17-producing T helper cells during HBV-related acute-on-chronic liver failure

AIM:To longitudinally investigate cytokine gene expression and protein levels in Th17 and Treg cells,to observe T-cell phenotypes during hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACHBLF)and to analyze changes in Th17 and Treg phenotypes during disease progression.METHODS:We measured the expression of seven Th17/Treg differentiation-related genes and serum concentrations of the corresponding cytokines in 18ACHBLF,18 chronic hepatitis B(CHB)disease controls and 10 healthy controls(HCs)by real-time quantitative pCR and enzyme linked immunosorbent assay.peripheral Th17 and Treg cell frequencies were analyzed by flow cytometry.RESULTS:From the onset of ACHBLF,patients presented with a conductive Th17 differentiation cytokine environment accompanied by high Th17 frequency and high serum IL-17 levels,which were sustained throughout the disease course.The Treg-related cytokine IL-2and Foxp3 were also up-regulated from disease onset,and Foxp3 gene expression showed a gradually increasing trend during ACHBLF.The circular phenotype of Treg and Th17 cells showed changes from the onset of ACHGLF.At disease onset,Th17 frequency increased significantly compared with both CHB and HCs,but Treg cell frequency decreased significantly compared with CHB.During the ACHBLF event,Th17 frequency remained higher compared with HCs,but decreased sharply from the peak point to the recovery point;Treg cell frequency increased gradually during the ACHBLF event.Treg and Th17 cell counts correlated with ACHBLF development;in all patients,serum IL-17 levels significantly correlated with patient serum ALT levels.In survivors,Th17 frequency at the onset point and the Treg to Th17 ratio at the peak point correlated with the patient’s model for end stage liver disease(MELD)plus sodium(MELD-Na)score.The Treg to Th17 ratio and the Th17 frequency at onset were significant predictors of patient survival.Low Treg/Th17 cell ratios at the onset predicted poor survival.Survivors exhibited an initial decrease in the circulating Treg/Th17 ratio from the onset to the peak time,and subsequently displayed a continuous increase.CONCLUSION:Treg and Th17 cells showed changes in genes,protein levels and T cell phenotypes during ACHBLF events.An increased Treg/Th17 ratio was associated with the survival of ACHBLF patients.

Helicobacter pylori infection:How does age influence the inflammatory pattern?

The inflammatory pattern during Helicobacter pylori(H.pylori)infection is changeable and complex.During childhood,it is possible to observe a predominantly regulatory response,evidenced by high concentrations of key cytokines for the maintenance of Treg responses such as TGF-β1 and IL-10,in addition to high expression of the transcription factor FOXP3.On the other hand,there is a predominance of cytokines associated with the Th1 and Th17 responses among H.pylori-positive adults.In the last few years,the participation of the Th17 response in the gastric inflammation against H.pylori infection has been highlighted due to the high levels of TGF-β1 and IL-17 found in this infectious scenario,and growing evidence has supported a close relationship between this immune response profile and unfavorable outcomes related to the infection.Moreover,this cytokine profile might play a pivotal role in the effectiveness of anti-H.pylori vaccines.It is evident that age is one of the main factors influencing the gastric inflammatory pattern during the infection with H.pylori,and understanding the immune response against the bacterium can assist in the development of alternative prophylactic and therapeutic strategies against the infection as well as in the comprehension of the pathogenesis of the outcomes related to that microorganism.

Upregulation of CD81 in trophoblasts induces an imbalance of Treg/Th17 cells by promoting IL-6 expression in preeclampsia

The disturbance of maternal immune tolerance to a semiallogeneic fetus is recognized as one of the key pathologies of preeclampsia(PE),in which an imbalance between the inflammation-limiting regulatory T cells(Tregs)and the inflammationmediating Th17 cells plays an essential role.Previously,we reported that the abnormal upregulation of tetraspannin CD81 in trophoblast cells(fetal component)participated in the pathogenesis of PE.However,as one of the potential immune regulatory molecules,whether CD81 induces PE by interfering with the balance of the maternal immune system has not yet been clarified.Thus,we investigated the relationship between the upregulation of CD81 in trophoblast cells and the imbalance of Treg and Th17 cells in mothers.Here,we demonstrated that upregulation of CD81 in trophoblast cells was accompanied by a decrease in Treg cells and an increase in Th17 cells in both the basal plate(placental maternal side)and peripheral blood of patients with PE.In vitro culture of naïve T cells with medium from the CD81-overexpressing trophoblast cell line HTR-8 resulted in enhanced differentiation of T cells into Th17 cells and decreased the formation of Tregs,which was dependent on the paracrine signaling of IL-6 in trophocytes,induced by CD81.In a CD81-induced PE rat model,we found a significant shift of T cell differentiation towards Th17 cells,and administration of IL-6 antibody mitigated the PE phenotype and the imbalance of the Treg/Th17 cells.These results define a vital regulatory cascade involving trophocyte-derived CD81,IL-6,and maternal Treg/Th17 cells in the pathogenesis of PE and suggests new therapeutic approaches based on CD81 and IL-6 downregulation to prevent human PE.

温针灸配合独活寄生汤治疗类风湿性关节炎临床研究

目的:探讨温针灸配合独活寄生汤治疗类风湿性关节炎(RA)的疗效及对辅助性T淋巴细胞17(Th_(17))/调节性T淋巴细胞(Tregs)平衡的影响,为其临床诊治提供参考。方法:选择80例类风湿性关节炎患者,随机分为对照组和观察组,每组40例。其中对照组给予常规西药治疗,观察组给予温针灸配合独活寄生汤联合治疗,治疗1个月。比较两组患者治疗前后病情活动指标、血清炎症因子及Th_(17)、Treg细胞、叉头状转录因子P3(Foxp3)及其磷酸化翼状头转录因子P3(p-Foxp3)表达水平差异,分析两组患者治疗后临床症状及体征改善情况,观察两组患者临床疗效。结果:与对照组比较,观察组中医证候评分、RA病情评价量表(DAS28)评分、晨僵时间、关节压痛数及关节肿胀数明显较低,临床疗效明显较高(P<0.05)。与治疗前比较,两组患者治疗后血清转化生长因子β(TGF-β)、白细胞介素10(IL-10)水平及Treg、Foxp3、p-Foxp3表达水平均明显升高,血清白细胞介素-17(IL-17)、C反应蛋白(CRP)、类风湿因子(RF)和红细胞沉降率(ESR)水平及Th_(17)/Treg、Th_(17)表达水平明显降低,且观察组更明显(P<0.05)。结论:温针灸配合独活寄生汤治疗类风湿性关节炎,可以更好地改善其临床体征及症状,通过对Th_(17)细胞和Treg细胞含量进行调节,改善免疫功能,并起到抗炎作用。

肺结节病发病机制研究进展

结节病是一种原因不明的多系统累及的肉芽肿性疾病,主要侵犯肺和淋巴系统,其次是眼部和皮肤.肉芽肿是最复杂的免疫反应之一,涉及多种细胞,且细胞分子间的相互作用随时间而动态变化.近年对结节病发病机制的新见解不断涌现,包括结节病的先天免疫、Th17细胞、Treg细胞、血清淀粉样蛋白A(serum amyloid A protein,SAA)和其他因素的作用.