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| 1 | Immune suppression in chronic hepatitis B infection associated liver disease: A review显示文摘Hepatitis B virus(HBV) infection is one the leading risk factors for chronic hepatitis, liver fibrosis, cirrhosis and hepatocellular cancer(HCC), which are a major global health problem. A large number of clinical studies have shown that chronic HBV persistent infection causes the dysfunction of innate and adaptive immune response involving monocytes/macrophages, dendritic cells, natural killer(NK) cells, T cells. Among these immune cells, cell subsets with suppressive features have been recognized such as myeloid derived suppressive cells(MDSC),NK-reg, T-reg, which represent a critical regulatory system during liver fibrogenesis or tumourigenesis. However, the mechanisms that link HBVinduced immune dysfunction and HBV-related liver diseases are not understood.In this review we summarize the recent studies on innate and adaptive immune cell dysfunction in chronic HBV infection, liver fibrosis, cirrhosis, and HCC, and further discuss the potential mechanism of HBV-induced immunosuppressive cascade in HBV infection and consequences. It is hoped that this article will help ongoing research about the pathogenesis of HBV-related hepatic fibrosis and HBV-related HCC. | Tian-Yang Li Yang Yang Guo Zhou Zheng-Kun Tu | 2019 | World Journal of Gastroenterology2019，25，27： | 69 |
| 2 | Restoring the Treg cell to Th17 cell ratio may alleviate HBV-related acute-on-chronic liver failure显示文摘AIM: To investigate the role of T helper 17 cells (Th17) and regulatory T cells (Treg) in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).METHODS: We enrolled 79 patients with HBV infection into the study, 50 patients with HBV-related ACLF and 29 patients with chronic hepatitis B (CHB), from the First Affiliated Hospital of Medical College from January 2009 to June 2012. The ACLF patients were diagnosed according to the criteria recommended by The 19th Conference of the Asian Pacific Association for the Study of the Liver in 2009. Twenty healthy individuals with a similar gender and age structures to the two patient groups were also included as the normal controls (NC). Of the 50 ACLF patients, 28 were subsequently classified as non-survivors: 19 patients died from multiorgan failure, 3 underwent liver transplantation, and 6 discontinued therapy during follow-up because of financial reasons. The remaining 22 ACLF patients whose liver and anticoagulation function recovered to nearly normal levels within the next 6 mo were classified as survivors. The number of circulating Treg and Th17 cells was determined upon diagnosis and during the 8th week of follow-up through flow cytometry. RESULTS: The percentage of circulating Treg cells in the ACLF group was significantly higher than that in the CHB group (5.50% ± 1.15% vs 3.30% ± 1.13%, P < 0.01). The percentages of circulating Th17 cells in the ACLF and the CHB groups were significantly higher than that in the NC group (6.32% ± 2.22% vs 1.56% ± 0.44%, P < 0.01; 3.53% ± 1.65% vs 1.56% ± 0.44%, P < 0.01). No significant difference in Treg cell to Th17 cell ratio was observed between the ACLF group and the CHB group (0.98 ± 0.44 vs 1.12 ± 0.64, P = 0.991), whereas those in the two HBV infection groups were significantly lower than that in the NC group (1.85 ± 1.22; both P < 0.01). The percentage of Treg cells in the survivors during the 8th week of follow-up was significantly lower than that during peak ACLF severity [total bilirubin (TBIL) peak] (3.45% ± 0.97% vs 5.18% ± 1.02%, P < 0.01). The percentage of Th17 cells in survivors during the 8th week of follow-up was significantly lower than that during the peak TBIL (2.89% ±0.60% vs 5.24% ± 1.46%; P < 0.01). The Treg cell to Th17 cell ratio during the 8 th week of follow-up was significantly higher than that during the TBIL peak (1.22 ± 0.36 vs 1.10 ± 0.54; P < 0.05). CONCLUSION: Restoring the Treg cell to Th17 cell ratio during the follow-up phase of ACLF could maintain the immune system at a steady state, which favours good prognosis. | Ying-Hua Niu Dong-Lin Yin Hong-Li Liu Rui-Tian Yi Yu-Cong Yang Hong-An Xue Tian-Yan Chen Shu-Lin Zhang Shu-Mei Lin Ying-Ren Zhao | 2013 | World Journal of Gastroenterology2013，19，26： | 36 |
| 3 | Astragalus polysaccharide attenuates rat experimental colitis by inducing regulatory T cells in intestinal Peyer's patches显示文摘AIM: To explore probable mechanism underlying the therapeutic effect of Astragalus polysaccharide(APS) against experimental colitis.METHODS: Thirty-two Sprague-Dawley rats were randomly divided into four groups. Colitis was induced with 2, 4, 6-trinitrobenzene sulfonic acid(TNBS). The rats with colitis were treated with 400 mg/kg of APS for 7 d. The therapeutic effect was evaluated by colonic weight, weight index of the colon, colonic length, and macroscopic and histological scores. The levels of regulatory T(Treg) cells in Peyer's patches were measured by flow cytometry, and cytokines in colonic tissue homogenates were analyzed using enzyme-linked immunosorbent assay. The expression of related orphan receptor-gt(ROR-gt), IL-23 and STAT-5a was measured by Western blot.RESULTS: After 7-d treatment with APS, the weight index of the colon, colonic weight, macroscopical and histological scores were decreased, while the colonic length was increased compared with the model group. The expression of interleukin(IL)-2, IL-6, IL-17, IL-23 and ROR-gt in the colonic tissues was down-regulated, but Treg cells in Peyer's patches, TGF-β and STAT5 a in the colonic tissues were up-regulated.CONCLUSION: APS effectively ameliorates TNBSinduced experimental colitis in rats, probably through restoring the number of Treg cells, and inhibiting IL-17 levels in Peyer's patches. | Hai-mei Zhao Yan Wang Xiao-Ying Huang min-fang Huang Rong Xu Hai-Yang Yue Bu-gao Zhou Hong-Yan Huang Qi-meng Sun Duan-Yong Liu | 2016 | World Journal of Gastroenterology2016，22，11： | 28 |
| 4 | Restoring homeostasis of CD4^+ T cells in hepatitis-B-virusrelated liver fibrosis显示文摘Immune-mediated liver injury is widely seen during hepatitis B virus(HBV) infection. Unsuccessful immune clearance of HBV results in chronic hepatitis and increases the risk of liver cirrhosis and hepatocellular carcinoma. HBV-related liver fibrosis(HBVLF),occurring as a result of HBV-induced chronic hepatitis,is a reversible,intermediate stage of chronic hepatitis B(CHB) and liver cirrhosis. Therefore,defining the pathogenesis of HBVLF is of practical significance for achieving better clinical outcomes. Recently,the homeostasis of CD4+ T cells was considered to be pivotal in the process of HBVLF. To better uncover the underlying mechanisms,in this review,we systematically retrospect the impacts of different CD4+T-cell subsets on CHB and HBVLF. We emphasize CD4+ T-cell homeostasis and the important balance between regulatory T(Treg) and T helper 17(Th17) cells. We discuss some cytokines associated with Treg and Th17 cells such as interleukin(IL)-17,IL-22,IL-21,IL-23,IL-10,IL-35 and IL-33,as well as surface molecules such as programmed cell death protein 1,cytotoxic T lymphocyte-associated antigen 4,T cell immunoglobulin domain and mucin domain-containing molecule 3 and cannabinoid receptor 2 that have potential therapeutic implications for the homeostasis of CD4+ T cells in CHB and HBVLF. | Li-Sha Cheng Yun Liu Wei Jiang | 2015 | World Journal of Gastroenterology2015，21，38： | 26 |
| 5 | High mobility group box-1 protein inhibits regulatory T cell immune activity in liver failure in patients with chronic hepatitis B显示文摘BACKGROUND:Liver failure in chronic hepatitis B(CHB) patients is a severe,life-threatening condition.Intestinal endotoxemia plays a significant role in the progress to liver failure.High mobility group box-1(HMGB1) protein is involved in the process of endotoxemia.Regulatory T(Treg) cells maintain immune tolerance and contribute to the immunological hyporesponsiveness against HBV infection.However,the roles of HMGB1 and Treg cells in the pathogenesis of liver failure in CHB patients,and whether HMGB1 affects the immune activity of Treg cells are poorly known at present,and so were explored in this study.METHODS:The levels of HMGB1 expression were detected by ELISA,real-time RT-PCR,and Western blotting,and the percentage of CD4+CD25+CD127low Treg cells among CD4+ cells was detected by flow cytometry in liver failure patients with chronic HBV infection,CHB patients,and healthy controls.Then,CD4+CD25+CD127low Treg cells isolated from the peripheral blood mononuclear cells from CHB patients were stimulated with HMGB1 at different concentrations or at various intervals.The effect of HMGB1 on the immune activity of Treg cells was assessed by a suppression assay of the allogeneic mixed lymphocyte response.The levels of forkhead box P3(Foxp3) expression in Treg cells treated with HMGB1 were detected by RT-PCR and Western blotting.RESULTS:A higher level of HMGB1 expression and a lower percentage of Treg cells within the population of CD4+ cells were found in liver failure patients than in CHB patients(82.6±20.1 μg/L vs.34.2±13.7 μg/L;4.55±1.34% vs.9.52± 3.89%,respectively).The immune activity of Treg cells was significantly weakened and the levels of Foxp3 expression were reduced in a dose-or time-dependent manner when Treg cells were stimulated with HMGB1 in vitro.CONCLUSIONS:The high level of HMGB1 and the low percentage of Treg cells play an important role in the pathogenesis of liver failure in patients with chronic HBV infection.Moreover,HMGB1 can weaken the immune activity of Treg cells.It is suggested that effectively inhibiting HMGB1 expression could be a feasible way to treat liver failure by suppressing endotoxemia and enhancing Treg cell activity. | Wang, Lu-Wen Chen, Hui Gong, Zuo-Jiong | 2010 | Hepatobiliary & Pancreatic Diseases International2010，9，5： | 23 |
| 6 | Th17 plasticity and its changes associated with inflammatory bowel disease显示文摘CD4 T helper(Th) cell differentiation into distinct T cell subsets is critical to the normal function of the immune system. Until recently,the paradigm held that na?ve T cells differentiated into distinct subsets under the guidance of environmental cues(e.g.,cytokines) and that once polarized,these cells were committed to a particular functional state. However,the existence of transdifferentiated T cell populations,which express signature transcription factors and cytokines associated with more than one Th subset,challenges the immutability of T helper subsets and suggests that plasticity is a feature of multifaceted immune responses. How this process impacts immune dysregulation in diseases such as inflammatory bowel diseases(IBD) and the machinery that underlies this process is far from fully understood. Interleukin(IL)-17 secreting helper T(Th17) cells have been heavily implicated in tissue-specific immune pathology including murine models of IBD,human Crohn's disease and ulcerative colitis. Plasticity within this subset is suggested by the existence of IL-17 secreting cells,which,can also secrete interferon-γ,the signature cytokine for Th1 cells or,can co-express the anti-inflammatory transcription factor forkhead box p3,a signature transcription factor of regulatory T cells. In this review we mainly discuss evidence for Th17 plasticity,mechanisms,which govern it,and highlight the potential to therapeutically target this process in human IBD. | Aito Ueno Abhisek Ghosh Daniel Hung Ji Li Humberto Jijon | 2015 | World Journal of Gastroenterology2015，21，43： | 23 |
| 7 | Immunosuppressive effects of rat mesenchymal stem cells:involvement of CD4^+ CD25^+ regulatory T cells显示文摘BACKGROUND:Recent studies show that mesenchymal stem cells(MSCs)have immunomodulatory properties. They suppress the immune response to alloantigen and modify the proliferation of T cells.CD4 + CD25 + regulatory T cells have strong immunomodulatory potential.However, little is known about the effects of rat MSCs(rMSCs)on the development of regulatory T cells. METHODS:MSCs were obtained from bone marrow of male Sprague-Dawley rats,and co-cultured with CD3 + T cells from allogeneic spleen cells.The proportion of CD4 + CD25 + regulatory T cells was analyzed by flow cytometry.To further confirm the immunosuppressive activity of rMSCs, we used MTT assay and flow cytometry of CD3 + T cells to investigate the proliferative responses of CD3 + T cells to mitogenic stimuli.Enzyme-linked immunosorbent assay was performed to detect alterations of the cytokines TNF-α, TGF-βand IL-10. RESULTS:The proliferation of CD3 + T cells decreased when co-cultured with rMSCs,and the degree of inhibition was concentration-dependent.The percentage of CD4 + CD25 + regulatory T cells increased when CD3 + T cells were co- cultured with different concentrations of rMSCs.The levels of pro-inflammatory cytokine(TNF-α)decreased while anti- inflammatory(TGF-β,IL-10)cytokines increased in mixed lymphocyte reaction. CONCLUSIONS:rMSCs inhibit allogeneic T cell proliferation in mixed cell cultures.This immunosuppressive effect seems to be mediated by inducing the generation of CD4 + CD25 + regulatory T cells and soluble factors. | Ye, Zhou Wang, Yan Xie, Hai-Yang Zheng, Shu-Sen | 2008 | Hepatobiliary & Pancreatic Diseases International2008，7，6： | 15 |
| 8 | Immunomodulation by mesenchymal stem cells:Interplay between mesenchymal stem cells and regulatory lymphocytes显示文摘Mesenchymal stem cells(MSCs) possess immunomodulatory properties, which confer enormous potential for clinical application. Considerable evidence revealed their efficacy on various animal models of autoimmune diseases, such as multiple sclerosis, systemic lupus erythematosus and uveitis. MSCs elicit their immunomodulatory effects by inhibiting lymphocyte activation and proliferation, forbidding the secretion of proinflammatory cytokines, limiting the function of antigen presenting cells, and inducing regulatory T(Treg) and B(Breg) cells. The induction of Treg and Breg cells is of particular interest since Treg and Breg cells have significant roles in maintaining immune tolerance. Several mechanisms have been proposed regarding to the MSCs-mediated induction of Treg and Breg cells. Accordingly, MSCs induce regulatory lymphocytes through secretion of multiple pleiotropic cytokines, cell-to-cell contact with target cells and modulation of antigen-presenting cells. Here, we summarized how MSCs induce Treg and Breg cells to provoke immunosuppression. | Oscar Ka-Fai Ma Koon Ho Chan | 2016 | World Journal of Stem Cells2016，8，9： | 15 |
| 9 | Immunomodulatory effect of human amniotic epithelial cells on restoration of ovarian function in mice with autoimmune ovarian disease显示文摘Autoimmune ovarian disease(AOD)is considered to be a major cause of premature ovarian failure(POF).The immunomodulatory properties of human amniotic epithelial cells(hAECs)have been studied in many disease models.We previously reported that hAECs restored ovarian function in chemotherapy-induced POF mice,but the immunomodulatory mechanism of hAECs is still unclear.To investigate the effect of hAECs on recipient mice,especially on regulatory Treg cells,hAECs and hAEC-conditioned medium(hAEC-CM)were intravenously injected into AOD mice immunized with zona pellucida protein 3 peptides(pZP3).Ovarian function was evaluated through estrous cycle,hormone secretion,follicle development,and cell apoptosis analysis.Immune cells including CD3,CD4,CD8 and Treg cells in the spleens were tested by flow cytometry.To elucidate the effect of hAEC-CM on macrophage function,inflammation model in vitrowas established in RAW264.7 cells induced by lipopolysaccharide(LPS).hAECs and hAEC-CM regulated estrous cycles,promoted follicle development,ameliorated cell apoptosis and fibrosis in ovaries of AOD mice.In addition,hAECs significantly reversed the decrease of pZP3-induced Treg cells in the spleens.In vitro,hAEC-CM significantly inhibited the inflammatory reaction induced by LPS in RAW264.7 cells via up-regulating the expression of M2 macrophage genes.Further study demonstrated that hAECsecreted transforming growth factor-beta and macrophage inhibitory factor played important roles in the macrophage polarization and migration under inflammatory stimulation.Taken together,hAECs restored ovarian function by up-regulating Treg cells in the spleens and reduced the inflammatory reaction via modulating the activated macrophage function in a paracrine manner in the ovaries of AOD mice. | Qiuwan Zhang Yating Huang Junyan Sun Tingting Gu Xiaoyan Shao Dongmei Lai | 2019 | Acta Biochimica et Biophysica Sinica2019，51，8： | 14 |
| 10 | Mechanism of immune tolerance induced by donor derived immature dendritic cells in rat high-risk corneal transplantation显示文摘AIM: To study the role of immature dendritic cells (imDCs) on immune tolerance in rat penetrating keratoplasty (PKP) in high -risk eyes and to investigate the mechanism of immune hyporesponsiveness induced by donor-derived imDCs. ·METHODS: Seventy-five SD rats (recipient) and 39 Wistar rats (donor) were randomly divided into 3 groups: control, imDC and mature dendritic cell (mDC) group respectively. Using a model of orthotopic corneal transplantation in which allografts were placed in neovascularized high -risk eyes of recipient rat. Corneal neovascularization was induced by alkaline burn in the central cornea of recipient rat. Recipients in imDC group or mDC group were injected donor bone marrow-derived imDCs or mDCs of 1 ×10 6 respectively 1 week before corneal transplantation via tail vein. Control rat received the same volume of PBS. In each group, 16 recipients were kept for determination of survival time and other 9 recipients were executed on day 3, 7 and 14 after transplantation. Cornea was harvested for hematoxylin - eosin staining and acute rejection evaluation, Western blot was used to detect the expression level of Foxp3. ·RESULTS: The mean survival time of imDC group was significantly longer than that of control and mDC groups (all P <0.05). The expression level of Foxp3 on CD4 + CD25 + T cells of imDC group (2.24 ±0.18) was significantly higher than that in the control (1.68 ±0.09) and mDC groups (1.46±0.13) (all P <0.05).·CONCLUSION: Donor -derived imDC is an effective treatment in inducing immune hyporesponsiveness in rat PKP. The mechanism of immune tolerance induced by imDC might be inhibit T lymphocytes responsiveness by regulatory T cells. | Xiao-Wei Gao Yan Fu Wen-Jing Li An-Jie Du Xia Li Xu-Dong Zhao | 2013 | International Journal of Ophthalmology(English edition)2013，6，3： | 11 |
| 11 | Curcumin improves regulatory T cells in gut-associated lymphoid tissue of colitis mice显示文摘AIM: To explore the probable pathway by which curcumin(Cur) regulates the function of Treg cells by observing the expression of costimulatory molecules of dendritic cells(DCs).METHODS: Experimental colitis was induced by administering 2, 4, 6-trinitrobenzene sulfonic acid(TNBS)/ethanol solution. Forty male C57BL/6 mice were randomly divided into four groups: normal, TNBS + Cur, TNBS + mesalazine(Mes) and TNBS groups. The mice in the TNBS + Cur and TNBS +Mes groups were treated with Cur and Mes, respectively, while those in the TNBS group were treated with physiological saline for 7 d. After treatment, the curative effect of Cur was evaluated by colonic weight, colonic length, weight index of the colon, and histological observation and score. The levels of CD4+CD25+Foxp3+ T cells(Treg cells) and costimulatory molecules of DCs were measured by flow cytometry. Also, related cytokines were analyzed by enzyme-linked immunosorbent assay. RESULTS: Cur alleviated inflammatory injury of the colonic mucosa, decreased colonic weigh and histological score, and restored colonic length. The number of Treg cells was increased, while the secretion of TNF-α, IL-2, IL-6, IL-12 p40, IL-17 and IL-21 and the expression of costimulatory molecules(CD205, CD54 [ICAM-1], TLR4, CD252[OX40 L], CD256 [RANK] and CD254 [RANK L]) of DCs were notably inhibited in colitis mice treated with Cur.CONCLUSION: Cur potentially modulates activation of DCs to enhance the suppressive functions of Treg cells and promote the recovery of damaged colonic mucosa in inflammatory bowel disease. | Hai-Mei Zhao Rong Xu Xiao-Ying Huang Shao-Min Cheng Min-Fang Huang Hai-Yang Yue Xin Wang Yong Zou Ai-Ping Lu Duan-Yong Liu | 2016 | World Journal of Gastroenterology2016，22，23： | 9 |
| 12 | Disrupted regulatory T cell homeostasis in inflammatorybowel diseases显示文摘In the gut, where billions of non-self-antigens from the food and the microbiota are present, the immune response must be tightly regulated to ensure both host protection against pathogenic microorganisms and the absence of immune-related pathologies. It has been well documented that regulatory T cells(Tregs) play a pivotal role in this context. Indeed, Tregs are able to prevent excessive inflammation, which can lead to the rupture of intestinal homeostasis observed in inflammatory bowel diseases(IBDs). Both the worldwide incidence and prevalence of such diseases have increased throughout the latter part of the 20^(th) century. Therefore, it is crucial to understand how Tregs suppress the colitogenic immune cells to establish new treatments for patients suffering from IBDs. In this review, we will first summarize the results obtained in animal model studies that highlight the importance of Tregs in maintaining intestinal homeostasis and describe the specific suppressive mechanisms involved. Next, our current knowledge about Tregs contribution to human IBDs will be reviewed, as well as the current therapeutic perspective on using Tregs for clinical IBD treatment and the challenges that remain to be resolved to ensure both the safety and effectiveness of these therapies in targeting this critical immune-regulatory cell population. | Christophe Pedros Fanny Duguet Abdelhadi Saoudi Marianne Chabod | 2016 | World Journal of Gastroenterology2016，22，3： | 9 |
| 13 | Establishment of Nasal Tolerance to Heat Shock Protein-60 Alleviates Atherosclerosis by Inducing TGF-β-dependent Regulatory T Cells显示文摘Mounting evidence supports that a newly identified regulatory T cell (Treg),CD4+LAP+ Treg,is associated with oral tolerance induction and following inhibition of atherosclerosis,but little is described about whether nasal tolerance to antigen likewise induces the novel Tregs production and the relevant antiatherosclerotic benefit.We investigated the effect of nasal administration of heat shock protein-60 (HSP60) on atherogenesis.HSP60 or phosphate buffer solution (PBS) was nasally adminis-tered to six-week-old male ApoE-/-mice.At the 10th week after the nasal administration,there was a significant decrease in atherosclerotic plaque areas of aortic roots in the HSP60-treated mice as com-pared with those in the PBS-treated mice.Atherosclerosis suppression was accompanied with a signifi-cant increase in CD4+LAP+ and CD4+CD25+Foxp3+ Tregs and a concurrently increased production of TGF-β in the HSP60-treated mice.The protective effect of HSP60 was offset by injection of anti-TGF-βantibody.It is concluded that nasal administration of HSP60 can inhibit atherosclerotic formation through immune tolerance which is established by Tregs depending on the induction of anti-inflammatory cytokine TGF-β.Immune tolerance induced by nasal administration of HSP60 may provide an alternative therapeutic method for atherosclerosis. | 李海禹 丁艳萍 易桂文 曾秋棠 杨文凯 | 2012 | Journal of Huazhong University of Science and Technology(Medical Sciences)2012，32，1： | 7 |
| 14 | Rapamycin ameliorates experimental autoimmune uveoretinitis by inhibiting Th1/Th2/Th17 cells and upregulating CD4+CD25+ Foxp3 regulatory T cells显示文摘· AIM: To determine the effects of rapamycin on experimental autoimmune uveoretinitis(EAU) and investigate of role of rapamycin on T cell subsets in the disease.·METHODS: EAU was induced in rats using peptides1169 to 1191 of the interphotoreceptor binding protein(IRBP). Rapamycin(0.2 mg/kg/d) was administrated by intraperitoneal injection for a consecutive 7d after immunization. Th1/Th2/Th17 cytokines, TGF-β1, and IL-6produced by lymphocyteswere measured by ELISA, while Th17 cells and CD4 +CD25 + regulatory T cells(Tregs)from rat spleen were detected by flow cytometry.·RESULTS: Intraperitoneal treatment immediately after immunization dramatically ameliorated the clinical course of EAU. Clinical responses were associated with reduced retinal inflammatory cell infiltration and tissue destruction. Rapamycin induced suppression of Th1/Th2/Th17 cytokines, including IFN-γ, IL-2, IL-17, IL-4, and IL-10 release from T lymphocytes of EAU rats, in vitro.Rapamycin also significantly increased TGF-β1production but had no effect on IL-6 productionof T lymphocytes from EAU rats in vitro. Furthermore,rapamycin decreased the ratio of Th17 cells/CD4 +T cells and upregulated Tregs in EAU, as detected by flow cytometry.·CONCLUSION: Rapamycin effectively interferes with T cell mediated autoimmune uveitis by inhibiting antigen-specific T cell functions and enhancing Tregs in EAU.Rapamycin is a promising new alternative as an adjunct corticosteroid-sparing agent for treating uveitis. | Li-Fei Yuan Guang-Da Li Xin-Jun Ren Hong Nian Xiao-Rong Li Xiao-Min Zhang | 2015 | International Journal of Ophthalmology(English edition)2015，8，4： | 7 |
| 15 | Promises and paradoxes of regulatory T cells in inflammatory bowel disease显示文摘Since their discovery two decades ago,CD4+CD25+Foxp3+ regulatory T cells(Tregs) have become the subject of intense investigation by immunologists. Unlike other T cells,which promote an immune response,Tregs actively inhibit inflammation when activated by their cognate antigen,thus raising hope that these cells could be engineered into a highly targeted,antigenspecific,immunosuppressant therapy. Although Tregs represent less than 10% of circulating CD4+T cells,they have been shown to play an essential role in preventing or limiting inflammation in a variety of animal models and human diseases. In particular,spontaneous intestinal inflammation has been shown to occur in the absence of Tregs,suggesting that there may be a Treg defect central to the pathogenesis of human inflammatory bowel disease(IBD). However,over the past decade,multiple groups have reported no qualitative or quantitative deficits in Tregs from the intestines and blood of IBD patients to explain why these cells fail to regulate inflammation in Crohn's disease and ulcerative colitis. In this review,we will discuss the history of Tregs,what is known about them in IBD,and what progress and obstacles have been seen with efforts to employ them for therapeutic benefit. | James D LordJ | 2015 | World Journal of Gastroenterology2015，21，40： | 6 |
| 16 | Regulatory T Cells and Their Clinical Applications in Antitumor Immunotherapy显示文摘Cancer is a potentially life-threatening disease characterized by the immortalization of tumor cells in the host. Immunotherapy has recently gained increasing interest among researchers due to its tremendous potential for preventing tumor progression and metastasis. Regulatory T cells (Tregs) are a subgroup of suppressive CD4^+ T cells that play a vital role in the maintenance of host immune homeostasis. Treg deficiency can induce severe autoimmune, hypersensitivity, and auto-inflammatory disorders, among other diseases. Tregs are commonly enriched in a tumor microenvironment, and a greater number of immune-suppressive Tregs often indicates a poorer prognosis;therefore, there is renewed interest in the function of Tregs and in their clinical application in antitumor immunotherapy. Accumulating strategies that focus on the depletion of Tregs have appeared to be effective in antitumor immunity. It is expected that Treg-targeting strategies will provide great opportunities for improving antitumor efficiency in combination with other therapeutics (e.g., chimeric antigen receptor T cell (CAR-T)-based cell therapy or immune checkpoint blockading). | Feng Xie Rui Liang Dan Li Bin Li | 2019 | Engineering2019，5，1： | 5 |
| 17 | Roles of Tregs in development of hepatocellular carcinoma:A meta-analysis显示文摘AIM:To assess systematically the association between regulatory T cells(Tregs)and hepatocellular carcinoma(HCC).METHODS:We searched Medline,Embase and Wanfang databases for literature on the populations of Tregs in HCC patients and controls,using the pooled OR and 95%CIs for assessment.There were no limitations with respect to publication date or language.The references of qualifying articles were also searched.We excluded studies with unclear data or overlapping studies.Twenty-three studies met our criteria,and the quality of these studies was assessed using the Scottish Intercollegiate Guidelines Network(SIGN).The meta-analysis of association between Tregs and HCC was undertaken using the random-effects approach,as described by DerSimonian and Laird.Subgroup analysis was performed when at least three studies were available.Potential publication bias was assessed by visual inspection of the funnel plot,and an asymmetric plot suggested possible publication bias.RESULTS:Twenty-three studies with a total of 1279HCC patients and 547 healthy volunteers as controls were enrolled.The frequency of circulating Tregs in HCC patients was 87%higher than in healthy controls(OR=1.87,95%CI:1.49-2.34).The frequency of Tregs in the HCC tumor microenvironment was significantly higher than that in tumor-surrounding tissue and biopsy specimens from healthy livers(OR=4.04,95%CI:2.10-7.79,P=0.000;OR=2.869,95%CI:2.16-3.82,P=0.000).However,subgroup analyses based on the different types of tumors or patient characteristics such as tumor size,tumor number orαfetoprotein(AFP)levels in HCC patients,showed that populations of Tregs as a whole were not significantly changed between groups(P>0.05 for all).CONCLUSION:There is an obvious association between Tregs and pathogenesis of HCC.Further welldesigned clinical studies are warranted to illustrate the potential role of Tregs in HCC. | Hong-Qiang Zhao Wei-Min Li Zhong-Qiou Lu Yong-Ming Yao | 2014 | World Journal of Gastroenterology2014，20，24： | 5 |
| 18 | Rapamycin combined with allogenic immature dendritic cells selectively expands CD4^+CD25^+Foxp3^+ regulatory T cells in rats显示文摘BACKGROUND:Dendritic cells(DCs) can initiate the expansion of regulatory T cells(Tregs),which play an indispensable role in inducing transplantation tolerance.Some studies have investigated the effect of the immunosuppressant rapamycin(Rapa) on Tregs in vitro.However,the in vivo effect of Rapa combined with immature DCs(iDCs) on Tregs is unknown.This study was undertaken to determine whether allogenic iDCs combined with a short course of Rapa have the ability to selectively expand the CD4 + CD25 + Foxp3 + Tregs in a rat model.METHODS:Brown Norway rats were injected intravenously with 2×10 6 Lewis iDCs followed by 1 mg/kg per day Rapa intraperitoneally for 7 consecutive days.On day 8,the levels of CD4 + CD25 + Foxp3 + Treg cells in peripheral blood and spleen cells were analyzed by flow cytometry.IL-2,IL-4,TGF-β1,and IFN-γ levels in serum were assessed by ELISA.The experimental animals were divided into four groups:control,Rapa-treated,iDC-treated,and combination-treated.RESULTS:CD4 + CD25 + Foxp3 + Tregs comprised 7%-8% of CD4 + T cells in control rats.Rapa combined with iDCs enhanced this percentage in the peripheral blood and spleen.However,the levels of Tregs did not significantly change after treatment with Rapa or iDCs alone.The levels of CD4 + CD25 Foxp3 + T cells and CD4 + CD25 + Foxp3 T cells in CD4 + T cells did not significantly change in the combined group.The TGF-β1 level in serum from the combined group increased significantly compared with the other groups.CONCLUSIONS:A significantly higher percentage of CD4 + CD25 + Foxp3 + Tregs was found in rats treated with allogenic iDCs and a short course of Rapa,along with an increase in the TGF-β1 level in serum.This improved protocol may be a promising therapeutic strategy to increase Tregs,which are beneficial to the induction of peritransplant tolerance. | Guo-Ying Wang Qi Zhang Yang Yang Wen-Jie Chen Wei Liu Nan Jiang Gui-Hua Chen chgh1955@263.net | 2012 | Hepatobiliary & Pancreatic Diseases International2012，11，2： | 4 |
| 19 | Regulating regulatory T cells to achieve transplant tolerance显示文摘BACKGROUND:Regulatory T cells(Tregs) play crucial roles in both induction and maintenance of tolerance. This active immune regulation may contribute not only to the control of immune responses to self-antigens and thereby prevent autoimmune diseases,but also the control of responses to non-self molecules in adaptive immunity. Numerous experimental and clinical studies indicate that manipulating the balance between regulatory and responder T cells is an effective strategy to control immune responsiveness after transplantation. DATA SOURCES:Literature search was conducted using PubMed on the related subjects. Part of the material was based on the most recent work in the authors' laboratory. RESULTS:We propose some new strategies to achieve transplant tolerance in rodent animals via manipulating Treg function,including using histone deacetylase(HDAC) inhibitor to regulate Foxp3 transcription and enhance Treg suppression,induction of Treg-sparing apoptosis via Nur77,and identification of the co-inhibitory molecule herpes virus entry mediator(HVEM) as an effector molecule for Treg function. CONCLUSION:Regulation of Treg function will definitely provide us very promising tools to achieve clinical tolerance in the future. | Wayne W. Hancock | 2007 | Hepatobiliary & Pancreatic Diseases International2007，6，4： | 4 |
| 20 | Tolerance in liver transplantation: Biomarkers and clinical relevance显示文摘Transplantation is the optimal treatment for end-stage organ failure,and modern immunosuppression has allowed important progress in short-term outcomes. However,immunosuppression poorly influences chronic rejection and elicits chronic toxicity in current clinical practice. Thus,a major goal in transplantation is to understand and induce tolerance. It is well established that human regulatory T cells expressing the transcription factor Fox P3 play important roles in the maintenance of immunological self-tolerance and immune homeostasis. The major regulatory T cell subsets and mechanisms of expansion that are critical for induction and long-term maintenance of graft tolerance and survival are being actively investigated. Likewise,other immune cells,such as dendritic cells,monocyte/macrophages or natural killer cells,have been described as part of the process known as 'operational tolerance'. However,translation of these results towards clinical practice needs solid tools to identify accurately and reliably patients who are going to be tolerant. In this way,a plethora of genetic and cellular biomarkers is raising and being validated worldwide in large multicenter clinical trials. Few of the studies performed so far have provided a detailed analysis of the impact of immunosuppression withdrawal on pre-existing complications derived from the long-term administration of immunosuppressive drugs and the side effects associated with them. The future of liver transplantation is aimed to develop new therapies which increase the actual low tolerant vs non-tolerant recipients ratio. | Alberto Baroja-Mazo Beatriz Revilla-Nuin Pascual Parrilla Laura Martínez-Alarcón Pablo Ramírez José Antonio Pons | 2016 | World Journal of Gastroenterology2016，22，34： | 4 |
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