Small molecule inhibitors of RORγt for Th17 regulation in inflammatory and autoimmune diseases / 药物分析学报

As a ligand-dependent transcription factor,retinoid-associated orphan receptor γt(RORyt)that controls T helper(Th)17 cell differentiation and interleukin(IL)-17 expression plays a critical role in the pro-gression of several inflammatory and autoimmune conditions.An emerging novel approach to the therapy of these diseases thus involves controlling the transcriptional capacity of RORyt to decrease Th17 cell development and IL-17 production.Several RORyt inhibitors including both antagonists and inverse agonists have been discovered to regulate the transcriptional activity of RORyt by binding to orthosteric-or allosteric-binding sites in the ligand-binding domain.Some of small-molecule inhibitors have entered clinical evaluations.Therefore,in current review,the role of RORyt in Th17 regulation and Th17-related inflammatory and autoimmune diseases was highlighted.Notably,the recently developed RORyt inhibitors were summarized,with an emphasis on their optimization from lead compounds,ef-ficacy,toxicity,mechanisms of action,and clinical trials.The limitations of current development in this area were also discussed to facilitate future research.

Research progress on the roles and mechanisms of γδT cells in periodontitis / 口腔疾病防治

@#Periodontitis is a chronic infectious disease that occurs in periodontal support tissues. Plaque microorganisms are its initiating factor, while local inflammation and alveolar bone loss resulting from periodontitis are the most common causes of tooth loss. Interleukin-17 (IL-17), which plays an important role in the immune response to periodontitis, mostly originates from T helper cell 17 (Th17) and γδT cells. In periodontitis, the role of Th17 cells has been demonstrated broadly, but the role of γδT cells was not revealed until recent years. As a highly heterogeneous group of T lymphocytes, γδT cells are considered a link between innate immunity and adaptive immunity. Studies have found that γδT cells are mostly distributed in the oral epithelium near the biofilm, where they can interact with microorganisms to produce IL-17, recruit neutrophils, macrophages, etc., and participate in the host immune response to periodontitis. They also play a role in the association between periodontitis and relevant systemic diseases. In addition, γδT cells have been proven to produce tissue repair-related factors with a protective effect against periodontitis. The possible mechanism of γδT cells in periodontitis is discussed in this review.

Shaoyaotang Alleviates Ulcerative Colitis by Regulating Th17/Treg Balance Through IL-6/STAT3 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the role of interleukin-6 （IL-6）/signal transducer and activator of transcription 3 （STAT3） pathway in the balance of T helper 17 （Th17）/regulatory T （Treg） cells in ulcerative colitis （UC） with internal dampness-heat accumulation syndrome and the intervention mechanism of Shaoyaotang. MethodA total of 60 SD rats were randomized into blank group （equivalent volume of normal saline）， model group （equivalent volume of normal saline）， western medicine control group （0.42 g·kg-1 mesalazine）， and low-dose （11.1 g·kg-1）， medium-dose （22.2 g·kg-1）， and high-dose （44.4 g·kg-1） Shaoyaotang groups. UC with internal dampness-heat accumulation syndrome was induced in rats with the compound method except for the blank group. The administration lasted 14 days for each group. At 24 h after the last administration， rats were killed and the spleen and colon tissues were separated. The histopathological changes of colon were observed based on hematoxylin and eosin （HE） staining and the levels of interleukin-17 （IL-17） and transforming growth factor-β1 （TGF-β1） in colon tissue were detected by immunohistochemistry （IHC）. Flow cytometry was employed to determine the levels of Th17/Treg cells in the spleen， and Western blot to measure the levels of IL-6 and STAT3 proteins in colon tissue. ResultCompared with the blank group， the model group had lesions such as congestion and erosion， low percentage of spleen Treg cells （P<0.01）， high percentage of Th17 cells （P<0.01）， and high levels of IL-6 and STAT3 proteins in colon tissue （P<0.01）. Compared with the model group， the administration groups showed alleviation of colon injury， high percentage of spleen Treg cells （P<0.05， P<0.01）， low percentage of Th17 cells （P<0.01）， and low levels of IL-6 and STAT3 proteins in colon tissue （P<0.01）. ConclusionShaoyaotang regulates the balance of Th17/Treg by inhibiting the IL-6/STAT3 pathway， thereby relieving the pathological damage of UC rats with internal dampness-heat accumulation syndrome and affecting their immune function.

Effects of Th17 and Treg cells with their balance on thyroid-associated ophthalmopathy / 国际眼科杂志(Guoji Yanke Zazhi)

Thyroid-associated ophthalmopathy(TAO)is an organ-specific autoimmune disease, which will cause a series of symptoms to significantly reduce the health level and life quality of patients. The pathogenesis of TAO has not been fully clarified. At present, there is a lack of unified and mature treatment scheme of it. Indeed, T-helper 17 lymphocyte(Th17)cells, regulatory T(Treg)cells and their imbalance are closely related to the immunological pathogenesis of TAO. It is currently believed that the cytokines secreted by Th17 cells can not only promote the inflammatory response of TAO and the fibrosis of orbital connective tissue, but also inhibit the adipogenic differentiation of TAO orbital connective tissue. In addition, Treg cells mainly exert immunosuppressive effect on TAO and delay the disease progression. At the same time, there is a dynamic balance relationship between Th17 and Treg cells, the imbalance of Th17/Treg cells can trigger the occurrence and development of TAO. This paper mainly expounds the influence mechanism of Th17, Treg cells and their balance on TAO, and analyzes the reasons for the differences between different research results, so as to provide some reference for the study of the pathogenesis and clinical treatment of TAO.

Expression of miR-106b-5p in children with primary immune thrombocytopenia and its correlation with T cells / 中国当代儿科杂志

OBJECTIVES@#To study the expression level of plasma miR-106b-5p in primary immune thrombocytopenia (ITP) and its correlation with the levels of T helper 17 cell (Th17) and regulatory T cell (Treg) and the Th17/Treg ratio.@*METHODS@#A total of 79 children with ITP (ITP group) and 40 healthy children (control group) were selected as subjects. According to the treatment response, the 79 children with ITP were divided into three groups: complete response (n=40), partial response (n=18), and non-response (n=21). Quantitative real-time PCR was used to measure the expression level of miR-106b-5p. Flow cytometry was used to measure the frequencies of Th17 and Treg, and the Th17/Treg ratio was calculated. The correlation of the expression level of plasma miR-106b-5p with the frequencies of Th17 and Treg and the Th17/Treg ratio was analyzed.@*RESULTS@#Compared with the control group, the ITP group had significantly higher levels of miR-106b-5p, Th17, and Th17/Treg ratio (P<0.05) and a significantly lower level of Treg (P<0.05). After treatment, the ITP group had significant reductions in the levels of miR-106b-5p, Th17, and Th17/Treg ratio (P<0.05) and a significant increase in the level of Treg (P<0.05). Compared with the partial response and non-response groups, the complete response group had significantly lower levels of miR-106b-5p, Th17, and Th17/Treg ratio (P<0.05) and a significantly higher level of Treg (P<0.05). The correlation analysis showed that in the children with ITP, the expression level of plasma miR-106b-5p was positively correlated with the Th17 level and the Th17/Treg ratio (r=0.730 and 0.816 respectively; P<0.001) and was negatively correlated with the Treg level (r=-0.774, P<0.001).@*CONCLUSIONS@#A higher expression level of miR-106b-5p and Th17/Treg imbalance may be observed in children with ITP. The measurement of miR-106b-5p, Th17, Treg, and Th17/Treg ratio during treatment may be useful to the evaluation of treatment outcome in children with ITP.

Effect of Asiaticoside on Expression of Th17/Treg Cells in DBA/1 Mice with Collagen-Induced Arthritis / 中国实验方剂学杂志

ObjectiveTo observe the effect of asiaticoside （AC） on the expression of T helper 17 （Th17） cells and regulatory T （Treg） cells in DBA/1 mice with collagen-induced arthritis （CIA）. MethodMale SPF DBA/1 mice were randomized into six groups according to body weight： control group， CIA group， methotrexate group （MTX group， ip， 0.5 mg·kg-1）， and AC low-， medium-， and high-dose groups （ig， 5， 15， 45 mg·kg-1， respectively）. Modeling was performed in rats other than the control group. To be specific， they were immunized with bovine type Ⅱ collagen and complete Freund's adjuvant on the first day and with bovine type Ⅱ collagen and incomplete Freund's adjuvant on the 21st day. Administration began on the day of the second immunization， once a day for 28 days. On the 49th day， related tissues were collected. Then， hematoxylin-eosin （HE） staining was performed to observe the pathological changes of the joints. Immunohistochemical method was used to detect the expression of interleukin-17 （IL-17） and forkhead box protein-3 （FoxP3）， the markers of Th17 and Treg cells， respectively， immunofluorescence double staining the expression of IL-17 and FoxP3 in CD4+T cells of mouse joint tissue， and flow cytometry the proportions of Th17 and Treg cells in mouse lymph nodes. ResultCompared with the control group， CIA group demonstrated joint disorder， damage of articular cartilage and bone， severe bone erosion （P<0.01）， increase in stained CD4 and IL-17 and the integral absorbance （IA） （P<0.01）， decrease in stained FoxP3 and the IA （P<0.01）， rise of Th17/Treg ratio （P<0.01）， elevation of Th17 expression in mouse lymph nodes （P<0.01）， and reduction in Treg expression （P<0.01）. Compared with CIA group， MTX group and three AC groups showed normal joints， alleviated bone erosion and damage， intact and smooth joint surface， and decrease in stained IL-17 and IA （P<0.05， P<0.01）， and MTX group and AC medium-dose and high-dose groups registered decrease in stained CD4 and IA （P<0.01） and reduction in Th17/Treg ratio （P<0.05， P<0.01）. Moreover， AC medium-dose and high-dose groups showed rise in stained FoxP3 and IA （P<0.05， P<0.01）. In the lymph nodes of mice， decrease in expression of Th17 cells （P<0.05， P<0.01） and the increase in expression of Treg cells （P<0.05， P<0.01） were observed in all the three AC group. ConclusionAC can regulate Th17/Treg balance by inhibiting the expression of Th17 cells and promoting the expression of Treg cells in CIA mice.

Immunomodulatory Mechanism of Kangxian Yixin Prescriptions on Autoimmune Injury Mice Based on Th17/Treg Cell Balance / 中国实验方剂学杂志

ObjectiveTo investigate the immunomodulatory mechanism of Kangxian Yixin prescription （KYP） on autoimmune injury mice and its relationship with the T helper 17 （Th17）/regulatory T cell （Treg） balance. MethodSixty healthy 8-week-old male BALBc mice were randomly divided into a normal group and an experimental group at a ratio of 1∶5. On the 0th， 7th， and 28th days， 0.2 mL of porcine cardiac myosin emulsion （containing 0.1 mg of porcine cardiac myosin） was subcutaneously injected into the groin， armpit， and back of the mice in the experimental group to induce an animal model of myocardial immune injury. Mice with myocardial immune injury were randomly divided into a model group （Model）， a KYP group （20.4 g·kg-1·d-1， ig）， and a valsartan group （12 mg·kg-1·d-1， ig）. Mice in the control group and the model group received the same amount of normal saline by gavage. After four weeks of intervention， the heart tissues were collected. Hematoxylin-eosin （HE） staining and Masson staining were used to detect pathological damage in heart tissues. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression of type B-type natriuretic peptide （BNP）， anti-cardiac antibody， interleukin-17 （IL-17）， and interleukin-10 （IL-10） in the serum of mice， and the expression levels of Th17 cells and Tregs in the spleen were detected by flow cytometry. The protein expression of B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X （Bax） in heart tissues was detected by Western blot， and the mRNA expression of retinoid-related orphan receptor gamma t （RORγt） and forkhead box P3 （FoxP3） in the spleen was detected by quantitative real-time polymerase chain reaction （Real-time PCR）. ResultCompared with the control group， the model group showed worsened pathological damage in heart tissues， elevated serum levels of BNP， anti-myocardial antibody， and IL-17， decreased serum expression of IL-10 （P<0.05）， increased expression of Th17 cells and reduced expression of Tregs in spleen tissues （P<0.05）， increased protein expression of Bax， diminished Bcl-2 protein expression， elevated Bax/Bcl-2 ratio， up-regulated mRNA expression of RORγt， dwindled mRNA expression of FoxP3， and elevated ratio of RORγt/FoxP3 （P<0.05）. Compared with the model group， the KYP group and the valsartan group displayed relieved pathological damage in heart tissues， decreased serum expression of BNP， anti-myocardial antibody， and IL-17， increased serum expression of IL-10 （P<0.05）， reduced expression of Th17 cells and increased Tregs in spleen tissues （P<0.05）， dwindled protein expression of Bax and elevated protein expression of Bcl-2 in heart tissues （P<0.05）， diminished Bax/Bcl-2 ratio， reduced mRNA expression of RORγt， up-regulated FoxP3， and down-regulated ratio of RORγt/FoxP3 （P<0.05）. ConclusionKYP may improve myocardial immune damage by regulating the Th17/Treg cell balance.

Moxibustion regulates T-regulatory/T-helper 17 cell balance by modulating the microRNA-221/suppressor of cytokine signaling 3 axis in a mouse model of rheumatoid arthritis / 中西医结合学报

OBJECTIVE@#Rheumatoid arthritis (RA) progression is associated with the balance of T-regulatory (Treg) and T-helper 17 (Th17) cells, while the role of microRNAs (miRs) in regulating Treg/Th17 cell balance has not been clarified. This study aimed to assess whether moxibustion could regulate Treg/Th17 cell balance by modulating the miR-221/suppressor of cytokine signaling 3 (SOCS3) axis in the RA mouse model.@*METHODS@#A mouse model of collagen-induced arthritis (CIA) was established in male DBA/1J mice. Twenty-two days after CIA induction, the mice received daily treatment with moxibustion for 12 times. Pathological scores were assessed according to the levels of synovial hyperplasia. The expression levels of cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-17 and IL-10 were analyzed in serum by enzyme-linked immunosorbent assay. The cluster of differentiation 4 (CD4+) splenocytes was analyzed by fluorescence-activated cell sorting. The expression levels of RA-related miRs and target genes were subsequently detected, and the target of miR-221 was confirmed by the dual-luciferase reporter assay.@*RESULTS@#It was revealed that moxibustion treatment decreased the pathological scores and downregulated the expression levels of IL-1β, IL-6, TNF-α, IFN-γ and IL-17, while upregulated the expression level of IL-10. The Treg/Th17 cell balance was regulated by moxibustion treatment. The expression level of miR-221 was suppressed by moxibustion treatment. Furthermore, SOCS3 was found as the direct target of miR-221, which mediated the function of moxibustion by regulating the Treg/Th17 cell balance.@*CONCLUSION@#Moxibustion therapy regulated the Treg/Th17 cell balance by modulating the miR-221/SOCS3 axis in the RA mouse model.

Clinical Efficacy of Qufeng Juanyin Decoction on Infantile Bronchial Asthma with Wind Phlegm Obstructing Lung Syndrome / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of Qufeng Juanyin Decoction on bronchial asthma in children （syndrome of wind phlegm blocking lung） during the stage of attack， and the regulatory effect on T helper cell 17 （Th17）/regulatory T cell （Treg） and related factors. Method:One hundred and thirty patients were randomly divided into observation group （65 cases） and control group （65 cases） by random number table. In control group， 61 cases completed the treatment， including 1 fell off or lost visit， 3 was eliminated because of breach of protocol. And in observation group， 63 patients completed the treatment， including 2 cases fell off or lost visit. Both of the groups got Budesonide suspension by atomizer， 1 mg/time， 2 times/day， and severe children were added with Terbutaline Sulfate Aerosol every morning and evening， 2 sprays/time. Patients in control group got Suhuang Zhike capsules， 2 grains/time， 3 times/day. Patients in observation group got Qufeng Juanyin Decoction， 1 dose/day. The course of treatment lasted for 7 days. Onset and mitigation times of asthma were recorded. And before and after treatment， pulmonary function was evaluated， and daily variation rate of peak expiratory flow （PEF）， first second expiratory flow as a percentage of expected （FEV₁%） and ratio of first second forced expiratory volume （FEV₁） and forced vital capacity （FVC） were recorded， and scores of syndrome of wind phlegm blocking lung and exhaled nitric oxide were detected. At the first week after the treatment， asthma control test in children （C-ACT） was made. Levels of Th17 cells， Treg cells， interleukin-17 （IL-17）， IL-6， IL-10， IL-22 and IL-35 were also detected. And the safety was evaluated. Result:Onset and mitigation times of asthma in observation group were shorter those in control group （<italic>P</italic><0.01）. The daily variation rate of PEF in observation group was lower than that in control group （<italic>P</italic><0.01）， while levels of FEV₁% and FEV₁/FVC were higher than those in control group （<italic>P</italic><0.01）. Asthma control in observation group was better than that in control group （<italic>Z</italic>=2.106， <italic>P</italic><0.05）. FeNO and score of syndrome of wind phlegm blocking lung were lower than those in control group （<italic>P</italic><0.01）. Levels of Th17， Th17/Treg， IL-17， IL-6 and IL-22 were lower than those in control group （<italic>P</italic><0.01）， whereas levels of proportion of Treg cells， IL-10 and IL-35 were higher than those in control group （<italic>P</italic><0.01）. The total effective rate in observation group was 96.83% （61/63）， which was better than 85.25% （52/61） in control group （<italic>χ</italic>²=5.141， <italic>P</italic><0.05）. And the total effective rate of traditional Chinese medicine （TCM） syndrome was 98.41% （62/63）， which was better than 86.89% （53/61） in control group （<italic>χ</italic>²=4.525， <italic>P</italic><0.05）. And there was no adverse reaction caused by Qufeng Juanyin Decoction. Conclusion:Qufeng Juanyin Decoction can shorten the course of disease， improve the lung function， regulate the expressions of Th17/Treg cells and related factors， promote the immune balance of Th17 / Treg， reduce airway inflammation and airway hyperresponsiveness， and effectively control the attack of asthma， with a good clinical efficacy and safety on bronchial asthma in children （syndrome of wind phlegm blocking lung） during the stage of attack.

Shaoyaotang Treats Ulcerative Colitis by Inhibiting HIF-1α and Regulating Th17/Treg Balance / 中国实验方剂学杂志

Objective:To explore the effect of hypoxia-inducible factor （HIF）-1<italic>α</italic> on T helper 17 （Th17）/regulatory T cell （Treg） balance in ulcerative colitis and the intervention mechanism of Shaoyaotang. Method:Forty-eight SD rats were randomly divided into normal group （normal saline）， model group， mesalazine group （0.42 g·kg^-1）， Shaoyaotang group （11.1 g·kg^-1）， inhibitor group ［2-methoxyestradiol （2ME₂）， 0.015 g·kg^-1］， and Shaoyaotang+inhibitor group. The ulcerative colitis model was induced by 2，4，6-trinitrobenzene sulfonic acid （TNBS）. The rats in all groups received corresponding treatments for 7 d， and the general condition and disease activity index （DAI） were observed. Hematoxylin-eosin （HE） staining was used to observe histopathological changes of the colon. Enzyme-linked immunosorbent assay （ELISA） was employed to detect serum levels of interleukin （IL）-10， IL-17， and IL-23 in rats. Western blot was used to detect the expression levels of forkhead box protein 3 （FoxP3）， retinoic acid-related orphan receptor <italic>γ</italic>t （ROR<italic>γ</italic>t）， and HIF-1<italic>α</italic> proteins in the colon tissue. Result:Compared with the normal group， the model group showed elevated disease activity index （DAI） score and pathological score for intestinal mucosa （<italic>P</italic><0.01）， reduced serum IL-10 level （<italic>P</italic><0.01）， up-regulated IL-17 and IL-23 levels （<italic>P</italic><0.01）， increased ROR<italic>γ</italic>t and HIF-1<italic>α</italic> expression （<italic>P</italic><0.01）， and decreased FoxP3 protein expression （<italic>P</italic><0.01）. Compared with the model group， the Shaoyaotang group displayed diminished DAI score and pathological score for intestinal mucosa （<italic>P</italic><0.05， <italic>P</italic><0.01）， increased serum IL-10 level （<italic>P</italic><0.01）， decreased IL-17 and IL-23 levels （<italic>P</italic><0.01）， dwindled protein levels of ROR<italic>γ</italic>t and HIF-1<italic>α </italic>（<italic>P</italic><0.01）， and up-regulated expression of FoxP3 （<italic>P</italic><0.01）. Compared with the inhibitor group， the Shaoyaotang group and the Shaoyaotang+inhibitor group exhibited significant differences in the expression of ROR<italic>γ</italic>t， FoxP3， and HIF-1<italic>α</italic> proteins （<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:Shaoyaotang could effectively treat ulcerative colitis， and the underlying mechanism of action might be related to the regulation of Th17/Treg rebalance by inhibiting HIF-1<italic>α</italic>.

Effect of Intervention with Traditional Chinese Medicine on Th17/Treg Balance in Psoriasis： A Review / 中国实验方剂学杂志

Psoriasis is an autoimmune disease presented in the context of inflammation， and it mainly results from proliferation and differentiation defects of keratinocytes and abnormal immune response. However， some cellular and molecular mechanisms remain unclear. Although a variety of drugs and physiotherapies are applicable to this disease， they can only be utilized for a short-term period considering their transient effect， high cost， and serious adverse reactions. It is difficult to achieve satisfactory long-term results in the treatment of psoriasis. With the development of network pharmacology and molecular biology and the modernization of traditional Chinese medicine （TCM）， the multi-component and multi-target characteristics of TCM have become prominent， promoting the in-depth research on TCM by doctors and scholars. Nevertheless， there is no detailed summarization on the mechanisms of TCM in interfering with T helper 17 （Th17）/regulatory T （Treg） cell balance to prevent and treat psoriasis. After reviewing the recent literature data， this paper has found that Chinese herbal monomers， active ingredients， and compounds obviously regulate the Th17/Treg axis in psoriasis. Th17 cells have a pro-inflammatory effect， while Treg cells are responsible for maintaining peripheral tolerance. They function in a mutually exclusive manner， and maintaining the Th17/Treg balance helps to effectively reduce inflammatory reaction and regulate immune homeostasis. As revealed by a series of clinical and experimental studies carried out based on the Th17/Treg axis in psoriasis， reducing the percentage of Th17 cells，increasing the percentage of Treg cells，and regulating the levels of related cytokines and transcription factors are conducive to alleviating inflammation and regaining immune homeostasis，which has provided new ideas for further elucidating the pathological mechanism of psoriasis and alternative plans for developing new treatments against psoriasis.

Changes and significance of the ratio of T helper 17 and regulatory T cell in peripheral blood of patients with coal-burning-borne arsenic poisoning / 中华地方病学杂志

Objective To observe the change of T helper 17 (Th17),regulatory T cell (Treg) as a percentage of lymphocytes and the Th17/Treg ratio in peripheral blood of patients with coal-burning-borne arsenic poisoning,and to explore the role of Th17 cells and Treg cells balance in arsenic-induced immune injury.Methods A case-control study was conducted to investigate 149 cases of arsenic poisoning in Yuzhang arsenic poisoning area in the southwestern Gnizhou Province,and the age was (50.69 ± 6.14) years old,including 94 males and 55 females.The diagnosis was based on the "Diagnosis of Endemic Arsenicosis" (WS/T 211-2015),and the cases were divided into mild arsenic poisoning group (39 cases),moderate arsenic poisoning group (54 cases) and severe arsenic poisoning group (56 cases);forty--one residents of non-arsenic exposed villages about 12 km away from the diseased area were collected as control group,the age was (45.76 ± 7.88) years old,including 12 males and 29 females.Hair samples and peripheral blood were collected from the subjects.The content of hair arsenic was detected by inductively coupled plasma mass spectrometry (ICP-MS).The percentages of Th17 cells and Treg cells in peripheral blood lymphocytes were detected by flow cytometry,and changes in the ratio of Th17/Treg in each group were analyzed.Results The hair arsenic contents in control,mild,moderate,and severe arsenic poisoning groups [median (quartile)] were 0.12 (0.08-0.18),0.20 (0.16-0.33),0.25 (0.18-0.41),0.28 (0.21-0.50) μg/g,and the differences were statistically significant between groups (H =52.22,P ＜ 0.01),and the hair arsenic content in each arsenic poisoning group was higher than that of the control group (P ＜ 0.05).The percentages of Th17 cells in peripheral blood lymphocytes of moderate and severe arsenic poisoning groups [(0.42 ± 0.21)％,(0.41 ± 0.23)％] were higher than that of the control group [(0.29 ± 0.16)％,P ＜ 0.05].The percentages of Treg cells in peripheral blood lymphocytes of mild,moderate and severe arsenic poisoning groups [(0.37 ± 0.18)％,(0.31 ± 0.19)％,(0.27 ± 0.18)％] were lower than that of the control group [(0.71 ± 0.20)％,P ＜ 0.05];with respect to the mild arsenic poisoning group,the percentage of Treg cells in severe arsenic poisoning group was reduced (P ＜ 0.05).The ratios of Th17/Treg in mild,moderate and severe arsenic poisoning groups (1.17 ± 0.63,1.56 ± 0.69,1.83 ± 0.85) were higher than that of the control group (0.43 ± 0.22,P ＜ 0.05);compared with mild arsenic poisoning group,the ratio of Th17/Treg in severe arsenic poisoning group was elevated (P ＜ 0.05).Correlation analysis showed that the hair arsenic content was positively correlated with the percentage of Th17 cells in peripheral blood lymphocytes and the ratio of Th17/Treg (r =0.323,0.608,P ＜ 0.05),and negatively correlated with the percentage of Treg cells in peripheral blood lymphocytes (r =-0.486,P ＜ 0.05).Conclusion Coal-burning-borne arsenic poisoning can cause the proportion of Th17 cells in the peripheral blood of patients to increase in lymphocytes,and the proportion of Treg cells in lymphocytes to decrease,which in turn changes the balance of Th17/Treg,resulting in weakened immune tolerance and disorder the regulation of inflammatory response,thus participates in the occurrence and development of arsenic-induced immune damage.

Roles of T helper 17 and regulatory T cell infiltration in hepatic injury induced by arsenic in rats / 中华地方病学杂志

Objective To investigate the infiltration of T helper 17 (Th17) and regulatory T cells (Treg) in the liver of rats exposed to arsenic,and to investigate the roles of Th17 and Treg in infiltration of liver injury induced by arsenic.Methods Thirty-two Wistar rats,half male and half female,were randomly divided into control,low,medium and high arsenic dose groups by body weight via the random number table method,8 rats per group.Rats in control group were given oral garage of deionized water,while other groups were given oral gavage doses of 2.00 g/L sodium arsenite (NaAsO2) according to their body weight for 6 days every week,the concentrations of NaAsO2 were 1.25,2.50 and 5.00 ml/kg,respectively.After 4 months,liver tissue samples of rats were collected,the content of arsenic in liver was determined by inductively coupled plasma mass spectrometry (ICP-MS);Hematoxylin-eosin staining (HE) method was used to observe the morphological changes of liver tissue in rats;the protein expressions of interleukin-17A (IL-17A,the imflammatory factor secreted by Th17 cells) and Forkhead Box P3 (Foxp3,the lineage-specific transcription factor of Treg cells) were measured with immunohistochemistry.Results ① Arsenic content in liver of low,medium,and high arsenic exposed groups [63.83 (52.79-80.26),59.16 (51.38-76.58),79.26 (69.59-107.44) μg/g] were higher than those of the control group [2.86 (1.76-3.56)μg/g,P ＜ 0.05],and the high arsenic dose group was higher than the medium arsenic dose group (P ＜ 0.05).② With increasing doses of arsenic,the numbers of inflammatory cells in the liver tissue of rats were increased,and the liver tissue of the high arsenic dose group showed vacuolar degeneration and pathological changes in some areas.③ Compared with the control group,low and medium arsenic dose groups (0.001 + 0.001,0.010 ± 0.020,0.030 ± 0.080),the expression of IL-17A protein in the liver in high arsenic dose group were significantly increased (0.220 ± 0.130,P ＜ 0.05),the differences were statistically significant between groups (F =14.776,P ＜0.05).The expressions of Foxp3 protein in the liver in low,medium,and high arsenic dose groups were significantly higher (0.270 ± 0.050,0.330 ± 0.040,0.320 ± 0.070) than that in the control group (0.070 ± 0.020),the differences were statistically significant between groups (F =56.990,P ＜ 0.05).④ There was a positive correlation between hepatic arsenic levels and protein levels of IL-17A and Foxp3 in liver (r =0.48,0.81,P ＜ 0.05).Conclusion Arsenic exposure can increase the content of arsenic in liver tissue of rats,which causes the changes of infiltration of Th17 and Treg cells,leading to the change of immune status,suggesting that Thl7 and Treg cells play an important role in the development of arsenic-induced immune injury.

Th17/IL-17 axis and kidney diseases / 中华实用儿科临床杂志

Th17 cell is a newly developed CD4 +T cell subsets,play a pro-inflammatory role and participate in the pathogenesis of many autoimmune diseases mainly through secretion of cytokines such as interleukin-17 (IL-17),many of the biological effects of Th17 cells are closely related to the IL-17,this article reviews the relation-ship between Th17/IL-17 axis and related cytokines and kidney the pathogenesis of disease,in order to more in-depth understanding of the pathogenesis of kidney disease,provide the basis for looking for new targets of diagnosis and treatment of kidney disease and new treatment strategies.

Levels of peripheral T helper17 cells and serum T helper17-related cytokines in patients with multiple sclerosis: a Meta-analysis / 中华风湿病学杂志

Objective To test whether T helper 17 (Th17) cells was involved in the pathogenesis of multiple sclerosis (MS) by conducting a meta-analysis of the researches documenting the levels of Th17 cells and Th17-related cytokines [interleukin (IL)-17,IL-23] in patients with MS.Methods We identified articles reporting proportion of Th17 cells and the serum levels of IL-17,IL-23 in MS patients by searching CNKI,Wanfang med online,Embase,PubMed,Cochrane,WebofKnowledge,Food and Drug Administration (FDA).gov,and ClinicalTrials.gov.We registered this study at the International Prospective Register of Systematic Reviews (PROSPERO) (number CRD42017059113).The evidence level of selected studies was identified by guidelines from the Oxford Center for Evidence-Based Medicine 2011.We employed the Newcastle-Ottawa Quality Assessment Scale (Case Control Studies) to perform the included resear.Stata 12.0 was adopted for processing Meta-analysis of the data by using a random effects model.Results A total 16 researches were included in our Meta-analysis from 587 identified studies.The proportion of Th17 cells [1.89％(1.10％,2.69％),P＜0.01] and the levels of serum IL-17 [2.77(1.77,3.77) pg/ml,P＜0.01] and IL-23 [2.96(1.51,4.40)pg/ml,P＜0.01] increased dramatically in MS individuals compared with control subjects.Conclusion The results of this Meta-analysis has demonstrated that MS patients have a higher proportion of Th 17 cells in higher levels of serum IL-17 and IL-23 compared to control subjects,which has demonstrated that Th17 cells may play an vital role in the pathogenesis process of MS patients.

T helper 17 cell in patients with rheumatoid arthritis mediated by interleukin-38 / 中华风湿病学杂志

Objective To investigate the effect of interleukin (IL)-38 on T helper 17 (Th17) cells in patients with rheumatoid arthritis (RA).Methods Total RNA were extracted and reverse transcribed into complementary DNA.Real-time polymerase chain reaction (PCR) technique was used to determine the gene expression of IL-38 at transcription level.Enzyme linked immune sorbent assay (ELISA) was used to detect the levels of IL-38 and IL-17 in peripheral blood.The percentage of peripheral blood Th17 cells was determined by Flow cytometry.Statistical analysis was conducted with t-test and Mann-Whitney U rank test.Results ① IL-38 mRNA expression from RA patients (2.9±4.0) was significantly reduced as compared with normal controls (5.8±3.6),(Z=-1.28,P＜0.05).IL-38 protein expression from RA patients (0.44±0.03) was lower than healthy controls (0.72±0.58),(Z=-1.59,P＜0.05).② The number of Th17 cells from RA patients (11.7±3.2) increased compared with healthy controls (7.9±2.3),(Z=-1.98,P＜0.05).The counts of Th17 cells from RA patients was negatively correlated with IL-38 (r=-0.38,P＜0.05).③ The level of peripheral blood IL-17 in RA (64±52) was significantly higher than normal controls (35±8),(Z=-2.17,P＜0.05).The level of IL-17 in RA was negatively correlated with IL-38 (r=-0.31,P＜0.05).④ IL-38 caused a significant decrease in the number of Th17 cells from RA patients (5.7±1.2) compared with untreated cells (7.9±2.3),(Z=-1.57,P＜0.05).Conclusion The decrease of IL-38 level in RA patients has resulted in the excessive activation of Th17 cells,which triggers the occurrence of RA.

Changes in myeloid-derived suppressor cells (MDSC), Treg and Th17 cells in peripheral blood of patients with cervical human papillomavirus (HPV) infection / 中华微生物学和免疫学杂志

Objective To investigate the changes in myeloid-derived suppressor cells (MDSC), regulatory T cells (Treg) and T helper 17 (Th17) cells in peripheral blood of patients with HPV infection and cervical diseases including ectopic cervical columnar epithelium (CE), cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CC), and to analyze the roles of MDSC, Treg and Th17 cells in the development of cervical diseases.Methods This study enrolled 120 HPV-positive patients with cervical diseases (18 cases of CE, 50 cases of CIN, 52 cases of CC), 20 HPV-negative patients with cervical diseases (10 cases of CE and 10 cases of CIN) and 20 healthy subjects from March 2011 to December 2016.Changes in MDSC, Treg and Th17 cells in peripheral blood of all patients were detected by flow cytometry.Results Percentages of MDSC, Treg and Th17 cells in peripheral blood of patients who were positive for HPV were significantly higher than those in HPV-negative patients (P<0.05).Besides, percentages of these cells gradually increased with the exacerbation of cervical disease (CE-CINⅠ-CINⅡ-CINⅢ-CC) (P<0.05).Patients who were infected with high-risk HPV had significantly higher percentages of MDSC, Treg and Th17 cells in peripheral blood than those infected with low-risk HPV (P<0.05).Changes of MDSC, Treg and Th17 cells in peripheral blood of HPV-positive patients with cervical cancer were related to International Federation of Gynecology and Obstetrics (FIGO) stage, tumor differentiation, lymph node metastasis and vascular invasion (P<0.05).MDSC, Treg and Th17 cells in peripheral blood of all patients were significantly reduced after treatment (P<0.05).Patients whose status changed from HPV-positive to HPV-negative following treatment also showed significantly decreased MDSC, Treg and Th17 cells in peripheral blood as compared with those who remained HPV-positive (P<0.05).MDSC, Treg and Th17 cells in peripheral blood of HPV-positive patients with cervical diseases were positively correlated (r=0.599, 0.677, 0.648;P<0.05).Conclusion MDSC, Treg and Th17 cells in peripheral blood of patients with HPV infection are associated with the pathological process, severity and clinical pathological features of cervical diseases as well as therapeutic effects.Therefore, they can be used as biomarkers to detect the occurrence and development of HPV-positive cervical diseases.

Effect of Dll4-Notch signaling pathway blockade on development of Th17 cells in asthmatic mice / 中国病理生理杂志

AIM:To explore the effect of Delta-like ligand 4 (Dll4)-Notch signaling pathway blockade on the development of Thelper 17(Th17) cells in the asthmatic mice.METHODS:Male BALB/c mice were randomly divided into 5 groups:control group, asthma group, normal saline group, anti-Dll4 antibody group, and immunoglobulin G group.The protein expression of Dll4 was detected by immunohistochemical staining.The proportion of Th17 cells in mouse spleen isolated CD4+ T cells was measured by flow cytometry.The protein expression of Th17 transcription factor retinoid-related orphan receptor γt (RORγt) was determined by Western blot.The serum level of interleukin (IL)-17 was measured by enzyme-linked immunosorbent assay (ELISA).RESULTS:The expression of Dll4 in the lung tissues from asthma group significantly increased as compared with anti-Dll4 antibody group.The proportion of Th17 cells in CD4+ T cells was significantly down-regulated, and the protein expression of RORγt in the lung tissues was significantly reduced in anti-Dll4 antibody group compared with asthma group (P<0.05).Moreover, the serum level of IL-17 in anti-Dll4 antibody group was significantly reduced compared with asthma group (P<0.01).CONCLUSION:The blockade of Dll4-Notch signaling pathway inhibits the differentiation of Th17 cells in asthmatic mice.

Roles of CD4 + CD25 + regulatory T cells and T helper 17 cells in the pathogenesis of Kawasaki disease / 中华实用儿科临床杂志

Objective To observe the changes in CD4 + CD25 + regulatory T cells(Treg) and T helper 17 cells (Th17) cells' proportions in the peripheral blood in children with Kawasaki disease(KD) before and after the treatment,and to analyze the role of Treg/Th17 cell imbalance in the pathogenesis of KD.Methods Fifty-two children with acute KD(KD group) and 34 age-matched healthy children(healthy control group) were selected at Jiangxi Provincial Children's Hospital from April to December of 2014.Morning peripheral vein blood was collected from 2 groups:one before the treatment by Immunoglobulin and Aspirin,and the other 3 days after defervescence treatment.Flow cytometry was used to detect proportions of Treg cells and Th17 cells in the peripheral blood.The enzyme linked immunosorbent assay was used to detect the levels of interleukin(IL)-6,IL-10,IL-17,IL-23 and transforming growth factor(TGF)-β.Results Proportion of Treg cells in the acute KD group was remarkably lower than that in the healthy control group [(1.48 ± 0.21) ％ vs.(5.13-± 0.32) ％,t =28.41,P ＜ 0.05],but it was significantly increased after treatment,and there was a significant difference [(4.71 ± 0.36) ％ vs.(1.48 ± 0.21) ％,t =-23.32,P ＜ 0.05].Proportion of Th17 cells in the acute KD group was markedly higher than that in the healthy control group [(8.06 ± 0.48) ％ vs.(2.65 ± 0.50) ％,t =-23.47,P ＜ 0.05],which was significantly decreased after treatment [(3.04 ±0.35) ％ vs.(8.06 ± 0.48) ％,t =25.55,P ＜ 0.05].Compared with the healthy control group,the levels of serum IL-6,IL-17,IL-23 in the acute KD group were significantly increased before treatment,and there were significant differences [(34.53 ± 0.53) ng/L vs.(10.88 ± 0.83) ng/L,t =-72.36;(57.05 ± 0.78) ng/L vs.(14.29 ± 0.98)ng/L,t =-55.29;(45.18 ± 1.52) ng/L vs.(18.25 ± 1.08) ng/L,t =-43.27;all P ＜ 0.05],but after treatment the levels were significantly decreased [(14.94 ± 1.06) ng/L vs.(34.53 ± 0.53) ng/L,t =49.63;(27.64 ± 0.91)ng/Lvs.(57.05±0.78) ng/L,t =26.49;(24.50-±1.13) ng/L vs.(45.18-±1.52) ng/L,t =32.17;allP＜0.05].The levels of serum IL-10,TGF-β in the acute KD group significantly decreased than those of the healthy control group,and there were significant differences [(14.29-± 0.64) ng/L vs.(29.57 ± 0.87) ng/L,t =42.24;(16.88 ±-0.90) ng/L vs.(38.83 ±0.84) ng/L,t =53.51;all P ＜0.05],but after treatment the levels were significantly increased,and there were significant differences [(23.01-± 0.61) ng/L vs.(14.29-± 0.64) ng/L,t =-29.54;(33.47±-0.82) ng/Lvs.(16.88±-0.90) ng/L,t=-40.68;allP＜0.05].Conclusion Imbalance betweenTreg cells and Th17 cells may be an important cause for the immune disorder of KD,the changes in related cytokines are involved in the pathogenesis of KD.

Study on the Th17 ,Th9 cells and the expression of the correlated cytokines in peripheral blood of patients with pediatric bronchial asthma and the clinical significance / 国际检验医学杂志

Objective To detect the levels of helper T cells (Th) 17 and Th9 cells in the peripheral blood of patients with pedi-atric bronchial asthma and the expression of interleukin 17 (IL-17) ,IL-9 and total IgE in serum ,and to discuss their effect and clini-cal significance in pathogenesis of pediatric asthma .Methods A total of 46 children with bronchial asthma ,including asthma attack group (n=26) and asthma remission group (n=20) were selected .Healthy children were selected as healthy control group (n=20) .Flow cytometry was used to detect the percentages of Th17 and Th9 cells in the peripheral blood .The levels of IL-17 and IL-9 in serum were measured by enzyme-linked immunosorbent assay (ELISA) .Serum total IgE levels were measured by the specific protein analyzer .Results The percentages of Th17 and Th9 cells in the peripheral blood were significantly higher in asthmatic group compared with remission group and healthy control group (P<0 .05) .The percentages of Th17 and Th9 cells in the periph-eral blood was significantly higher in remission group compared with healthy control group (P<0 .05) .The levels of IL-17 ,IL-9 and total IgE in serum were significantly higher in asthmatic group compared with remission group and healthy control group (P<0 .05) .The levels of IL-17 ,IL-9 and total IgE in serum were significantly higher in remission group compared with healthy control group (P<0 .05) .The levels of IL-17 and IL-9 in serum of asthmatic children were positively correlated with total IgE levels (P<0 .05) .The correlation analysis results showed that the levels of IL-17 ,IL-9 and total IgE in serum of patients with pediatric bron-chial asthma have a positive correlation .(r=0 .717 ,0 .491 ,0 .786 ,P<0 .05) .Conclusion Th17 ,Th9 cells and their cytokines in pe-ripheral blood of patients with pediatric bronchial asthma play important roles in the pathogenesis of asthma and are positively cor-related with the severity of asthma .