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Stem cell-like memory T cells:Role in viral infections and autoimmunity
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作者 Meenakshi Sachdeva Shivangi Taneja Naresh Sachdeva 《World Journal of Immunology》 2023年第2期11-22,共12页
Stem cell-like memory T(TSCM)cells possess stem cell properties including multipotency and self-renewal and are being recognized as emerging players in various human diseases.Advanced technologies such as multiparamet... Stem cell-like memory T(TSCM)cells possess stem cell properties including multipotency and self-renewal and are being recognized as emerging players in various human diseases.Advanced technologies such as multiparametric flowcytometry and single cell sequencing have enabled their identification and molecular characterization.In case of chronic viral diseases such as human immunodeficiency virus-1,CD4+T_(SCM) cells,serve as major reservoirs of the latent virus.However,during immune activation and functional exhaustion of effector T cells,these cells also possess the potential to replenish the pool of functional effector cells to curtail the infection.More recently,these cells are speculated to play important role in protective immunity following acute viral infections such as coronavirus disease 2019 and might be amenable for therapeutics by ex vivo expansion.Similarly,studies are also investigating their pathological role in driving autoimmune responses.However,there are several gaps in the understanding of the role of T_(SCM) cells in viral and autoimmune diseases to make them potential therapeutic targets.In this minireview,we have attempted an updated compilation of the dyadic role of these complex T_(SCM) cells during such human diseases along with their biology and transcriptional programs. 展开更多
关键词 stem cell-like memory t cells Viral infections Autoimmune diseases Effector t cells memory t cells
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Immunomodulation of adipose-derived mesenchymal stem cells on peripheral blood mononuclear cells in colorectal cancer patients with COVID-19
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作者 Jun-Feng Wang Xiao-Xia Yang +4 位作者 Jian Zhang Yan Zheng Fu-Qing Zhang Xiao-Feng Shi Yu-Liang Wang 《World Journal of Gastrointestinal Oncology》 SCIE 2024年第5期2113-2122,共10页
BACKGROUND Accumulating evidence has shown that adipose tissue-derived mesenchymal stem cells(ADSCs)are an effective therapeutic approach for managing coronavirus disease 2019(COVID-19);however,further elucidation is ... BACKGROUND Accumulating evidence has shown that adipose tissue-derived mesenchymal stem cells(ADSCs)are an effective therapeutic approach for managing coronavirus disease 2019(COVID-19);however,further elucidation is required to determine their underlying immunomodulatory effect on the mRNA expression of T helper cell-related transcription factors(TFs)and cytokine release in peripheral blood mononuclear cells(PBMCs).AIM To investigate the impact of ADSCs on the mRNA expression of TFs and cytokine release in PBMCs from colorectal cancer(CRC)patients with severe COVID-19(CRC^(+)patients).METHODS PBMCs from CRC^(+)patients(PBMCs-C+)and age-matched CRC patients(PBMCs-C)were stimulated and cultured in the presence/absence of ADSCs.The mRNA levels of T-box TF TBX21(T-bet),GATA binding protein 3(GATA-3),RAR-related orphan receptor C(RORC),and forkhead box P3(FoxP3)in the PBMCs were determined by reverse transcriptase-polymerase chain reaction.Culture supernatants were evaluated for levels of interferon gamma(IFN-γ),interleukin 4(IL-4),IL-17A,and transforming growth factor beta 1(TGF-β1)using an enzyme-linked immunosorbent assay.RESULTS Compared with PBMCs-C,PBMCs-C+exhibited higher mRNA levels of T-bet and RORC,and increased levels of IFN-γ and IL-17A.Additionally,a significant decrease in FoxP3 mRNA and TGF-β1,as well as an increase in Tbet/GATA-3,RORC/FoxP3,IFN-γ/IL-4,and IL-17A/TGF-β1 ratios were observed in PBMCs-C+.Furthermore,ADSCs significantly induced a functional regulatory T cell(Treg)subset,as evidenced by an increase in FoxP3 mRNA and TGF-β1 release levels.This was accompanied by a significant decrease in the mRNA levels of T-bet and RORC,release of IFN-γ and IL-17A,and T-bet/GATA-3,RORC/FoxP3,IFN-γ/IL-4,and IL-17A/TGF-β1 ratios,compared with the PBMCs-C+alone.CONCLUSION The present in vitro studies showed that ADSCs contributed to the immunosuppressive effects on PBMCs-C+,favoring Treg responses.Thus,ADSC-based cell therapy could be a beneficial approach for patients with severe COVID-19 who fail to respond to conventional therapies. 展开更多
关键词 Colorectal cancer COVID-19 Adipose-derived mesenchymal stem cells t helper cell IMMUNOMODULAtION
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UBE2T mediates the stemness properties of breast cancer cells through the mTOR signaling pathway
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作者 JIAWEI YIN YONGSHENG WANG +1 位作者 GUANGWEI WEI MINGXIN WEN 《BIOCELL》 SCIE 2024年第6期959-970,共12页
Objectives:This study aimed to reveal the role and possible mechanism of the ubiquitin-conjugating enzyme 2T(UBE2T)in the biological activities of breast cancer stem cells(BCSCs).Methods:The specific protein and gene ... Objectives:This study aimed to reveal the role and possible mechanism of the ubiquitin-conjugating enzyme 2T(UBE2T)in the biological activities of breast cancer stem cells(BCSCs).Methods:The specific protein and gene expression were quantified by Western blotting and quantitative real-time polymerase chain reaction,the proportion of BCSCs was examined by flow cytometry,and the self-renewal and proliferation of BCSCs were verified by serial sphere formation and soft agar.Results:Increasing expression of UBE2T was drastically found in breast cancer than that in adjacent tissues.Furthermore,UBE2T overexpression significantly increased the proportion of BCSCs in breast cancer cells and promoted their self-renewal and proliferation.Silent UBE2T exhibited the opposite functions.UBE2T increased the levels of the mammalian target of rapamycin and the phosphorylated mammalian target of rapamycin.Mammalian target of rapamycin(mTOR)inhibitor rapamycin inhibited the function of UBE2T in BCSCs.Conclusion:UBE2T plays a role in BCSCs through mTOR pathway and may suggest a novel therapeutic strategy for breast cancer. 展开更多
关键词 UBE2t Breast cancer Breast cancer stem cell MtOR
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Deer antler stem cell niche: An interesting perspective 被引量:1
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作者 Claudia Cavallini Elena Olivi +5 位作者 Riccardo Tassinari Chiara Zannini Gregorio Ragazzini Martina Marcuzzi Valentina Taglioli Carlo Ventura 《World Journal of Stem Cells》 SCIE 2024年第5期479-485,共7页
In recent years,there has been considerable exploration into methods aimed at enhancing the regenerative capacity of transplanted and/or tissue-resident cells.Biomaterials,in particular,have garnered significant inter... In recent years,there has been considerable exploration into methods aimed at enhancing the regenerative capacity of transplanted and/or tissue-resident cells.Biomaterials,in particular,have garnered significant interest for their potential to serve as natural scaffolds for cells.In this editorial,we provide commentary on the study by Wang et al,in a recently published issue of World J Stem Cells,which investigates the use of a decellularized xenogeneic extracellular matrix(ECM)derived from antler stem cells for repairing osteochondral defects in rat knee joints.Our focus lies specifically on the crucial role of biological scaffolds as a strategy for augmenting stem cell potential and regenerative capabilities,thanks to the establishment of a favorable microenvironment(niche).Stem cell differen-tiation heavily depends on exposure to intrinsic properties of the ECM,including its chemical and protein composition,as well as the mechanical forces it can generate.Collectively,these physicochemical cues contribute to a bio-instructive signaling environment that offers tissue-specific guidance for achieving effective repair and regeneration.The interest in mechanobiology,often conceptualized as a form of“structural memory”,is steadily gaining more validation and momen-tum,especially in light of findings such as these. 展开更多
关键词 Extracellular matrix Antler stem cells stem cell niche Regenerative medicine Decellularized scaffolds cell memory
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Comprehensive Understanding of Immune Cells in The Pathogenesis of Non-alcoholic Fatty Liver Disease
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作者 OUYANG Fei-Fan RASHEED Madiha +1 位作者 LI Bo DENG Yu-Lin 《生物化学与生物物理进展》 SCIE CAS CSCD 北大核心 2024年第9期2082-2100,共19页
Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease,defined by several phases,ranging from benign fat accumulation to non-alcoholic steatohepatitis(NASH),which can lead to liver cancer and... Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease,defined by several phases,ranging from benign fat accumulation to non-alcoholic steatohepatitis(NASH),which can lead to liver cancer and cirrhosis.Although NAFLD is a disease of disordered metabolism,it also involves several immune cell-mediated inflammatory processes,either promoting and/or suppressing hepatocyte inflammation through the secretion of pro-inflammatory and/or anti-inflammatory factors to influence the NAFLD process.However,the underlying disease mechanism and the role of immune cells in NAFLD are still under investigation,leaving many open-ended questions.In this review,we presented the recent concepts about the interplay of immune cells in the onset and pathogenesis of NAFLD.We also highlighted the specific non-immune cells exhibiting immunological properties of therapeutic significance in NAFLD.We hope that this review will help guide the development of future NAFLD therapeutics. 展开更多
关键词 non-alcoholic fatty liver disease metabolically associated fatty liver disease(MAFLD) t cells myeloid cells mesenchymal stem cells
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New insights into the biological roles of immune cells in neural stem cells in post-traumatic injury of the central nervous system 被引量:3
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作者 Ning He Xing-Jia Mao +3 位作者 Yue-Min Ding Tong Zuo Ying-Ying Chen Lin-Lin Wang 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第9期1908-1916,共9页
Traumatic injuries in the central nervous system,such as traumatic brain injury and spinal cord injury,are associated with tissue inflammation and the infiltration of immune cells,which simultaneously affect the self-... Traumatic injuries in the central nervous system,such as traumatic brain injury and spinal cord injury,are associated with tissue inflammation and the infiltration of immune cells,which simultaneously affect the self-renewal and differentiation of neural stem cells.Howeve r,the tissue repair process instigated by endogenous neural stem cells is incapable of restoring central nervous system injuries without external intervention.Recently,resident/peripheral immune cells have been demonstrated to exert significant effects on neural stem cells.Thus,the resto ration of traumatic injuries in the central nervous system by the immune intervention in neural stem cells represents a potential therapeutic method.In this review,we discuss the roles and possible mechanisms of immune cells on the selfrenewal and differentiation of neural stem cells along with the prognosis of central nervous system injuries based on immune intervention.Finally,we discuss remaining research challenges that need to be considered in the future.Further elucidation of these challenges will fa cilitate the successful application of neural stem cells in central nervous system injuries. 展开更多
关键词 B cells central nervous system injury MACROPHAGES MICROGLIA neural stem cells spinal cord injury t cells traumatic brain injury
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Pien Tze Huang alleviates Concanavalin A-induced autoimmune hepatitis by regulating intestinal microbiota and memory regulatory T cells
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作者 Xin Zeng Miao-Hua Liu +6 位作者 Yi Xiong Lin-Xin Zheng Kai-En Guo Hai-Mei Zhao Yu-Ting Yin Duan-Yong Liu Bu-Gao Zhou 《World Journal of Gastroenterology》 SCIE CAS 2023年第45期5988-6016,共29页
BACKGROUND Traditional Chinese medicine has used the drug Pien Tze Huang(PTH),a classic prescription,to treat autoimmune hepatitis(AIH).However,the precise mode of action is still unknown.AIM To investigate the mechan... BACKGROUND Traditional Chinese medicine has used the drug Pien Tze Huang(PTH),a classic prescription,to treat autoimmune hepatitis(AIH).However,the precise mode of action is still unknown.AIM To investigate the mechanism of PTH in an AIH mouse model by determining the changes in gut microbiota structure and memory regulatory T(mTreg)cells functional levels.METHODS Following induction of the AIH mouse model induced by Concanavalin A(Con A),prophylactic administration of PTH was given for 10 d.The levels of mTreg cells were measured by flow cytometry,and intestinal microbiota was analyzed by 16S rRNA analysis,while western blotting was used to identify activation of the toll-like receptor(TLR)2,TLR4/nuclear factor-κB(NF-κB),and CXCL16/CXCR6 signaling pathways.RESULTS In the liver of mice with AIH,PTH relieved the pathological damage and reduced the numbers of T helper type 17 cells and interferon-γ,tumor necrosis factor-alpha,interleukin(IL)-1β,IL-2,IL-6,and IL-21 expression.Simultaneously,PTH stimulated the abundance of helpful bacteria,promoted activation of the TLR2 signal,which may enhance Treg/mTreg cells quantity to produce IL-10,and suppressed activation of the TLR4/NF-κB and CXCL16/CXCR6 signaling pathways.CONCLUSION PTH regulates intestinal microbiota balance and restores mTreg cells to alleviate experimental AIH,which is closely related to the TLR/CXCL16/CXCR6/NF-κB signaling pathway. 展开更多
关键词 Pien tze Huang Autoimmune hepatitis Intestinal microbiota memory regulatory t cell toll-like receptor signaling
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Memory stem T cells generated by Wnt signaling from blood of human renal clear cell carcinoma patients 被引量:4
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作者 Cihui Yan Jingjing Chang +6 位作者 Xinmiao Song Fan Yan Wenwen Yu Yang An Feng Wei Lili Yang Xiubao Ren 《Cancer Biology & Medicine》 SCIE CAS CSCD 2019年第1期109-120,共12页
Objective: Memory stem T cells(Tscm) have attracted attention because of their enhanced self-renewal, multipotent capacity, and anti-tumor capacities. However, little is known about Tscm in patients with renal clear c... Objective: Memory stem T cells(Tscm) have attracted attention because of their enhanced self-renewal, multipotent capacity, and anti-tumor capacities. However, little is known about Tscm in patients with renal clear cell carcinoma(RCC) and the role of Wnt signaling in these cells. We evaluated Tscm from RCC patients concerning their activation of Wnt signaling in vitro and explored the mechanism of preferential survival.Methods: Flow cytometry identified surface markers and cytokines produced from accumulated Tscm in the presence of the glycogen synthase kinase beta inhibitor TWS119. Apoptosis was evaluated after induction using tumor necrosis factor-alpha.Immunofluorescence and Western blot analyses were used to investigate the activation of the nuclear factor-kappa B(NF-КB)pathway.Results: RCC patients had a similar percentage of CD4^+ and CD8^+ Tscm as healthy donors. Activation of Wnt signaling by TWS119 resulted in the accumulation of Tscm in activated T cells, but reversal of differentiated T cells to Tscm was not achieved.Preferential survival of Tscm was associated with increased anti-apoptotic ability mediated downstream of the NF-КB activation pathway.Conclusions: The finding that Tscm can accumulate by Wnt signaling in vitro in blood from RCC patients will help in devising new cancer therapy strategies of Tscm-based adoptive immunotherapy, such as dendritic cell-stimulated Tscm, and T cell receptor or chimeric antigen receptor-engineered Tscm. 展开更多
关键词 memory stem t cell tWS119 WNt signaling apoptosis RENAL CLEAR cell carcinoma
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Astrocytic endothelin-1 overexpression impairs learning and memory ability in ischemic stroke via altered hippocampal neurogenesis and lipid metabolism 被引量:3
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作者 Jie Li Wen Jiang +9 位作者 Yuefang Cai Zhenqiu Ning Yingying Zhou Chengyi Wang Sookja Ki Chung Yan Huang Jingbo Sun Minzhen Deng Lihua Zhou Xiao Cheng 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第3期650-656,共7页
Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However... Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction. 展开更多
关键词 astrocytic endothelin-1 dentate gyrus differentially expressed proteins HIPPOCAMPUS ischemic stroke learning and memory deficits lipid metabolism neural stem cells NEUROGENESIS proliferation
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Immunomodulation by mesenchymal stem cells:Interplay between mesenchymal stem cells and regulatory lymphocytes 被引量:15
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作者 Oscar Ka-Fai Ma Koon Ho Chan 《World Journal of Stem Cells》 SCIE CAS 2016年第9期268-278,共11页
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... 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. 展开更多
关键词 MESENCHYMAL stem cells REGULAtORY t cells REGULAtORY B cells IMMUNOMODULAtION AUtOIMMUNItY
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Immunosuppressive properties of cloned bone marrow mesenchymal stem cells 被引量:34
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作者 Robert C Zhao 《Cell Research》 SCIE CAS CSCD 2007年第3期240-248,共9页
Mesenchymal stem cells (MSCs), derived from adult tissues, are multipotent progenitor cells, which hold great promise for regenerative medicine. Recent studies have shown that MSCs are immunosuppressive in vivo and ... Mesenchymal stem cells (MSCs), derived from adult tissues, are multipotent progenitor cells, which hold great promise for regenerative medicine. Recent studies have shown that MSCs are immunosuppressive in vivo and in vitro in both animals and humans. However, the mechanisms that govern these immune modulatory functions of MSCs remain largely elusive. Some studies with bulk populations of MSCs indicated that soluble factors such as PGE2 and TGFβ are important, while others support a role for cell-cell contact. In this study, we intended to clarify these issues by examining immunosuppressive effects of cloned MSCs. We derived MSC clones from mouse bone marrow and showed that the majority of these clones were able to differentiate into adipocytes and osteoblast-like cells. Importantly, cells from these clones exhibited strong inhibitory effects on TCR activation-induced T cell proliferation in vitro, and injection of a small number of these cells promoted the survival of allogeneic skin grafts in mice. Conditioned medium from MSC cultures showed some inhibitory effect on anti-CD3 induced lymphocyte proliferation independent of PGE2 and TGFβ. In comparison, direct co-culture of MSCs with stimulated lymphocytes resulted in much stronger immunosuppressive effect. Interestingly, the suppression was bi-directional, as MSC proliferation was also reduced in the presence of lymphocytes. Taking together, our findings with cloned MSCs demonstrate that these cells exert their immunosuppressive effects through both soluble factor(s) and cell-cell contact, and that lymphocytes and MSCs are mutually inhibitory on their respective proliferation. 展开更多
关键词 SUPPRESSION t cells CYtOKINES stem cells tRANSPLANtAtION
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A ginkgo biloba extract promotes proliferation of endogenous neural stem cells in vascular dementia rats 被引量:13
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作者 Jiwei Wang Wen Chen Yuliang Wang 《Neural Regeneration Research》 SCIE CAS CSCD 2013年第18期1655-1662,共8页
The ginkgo biloba extract EGb761 improves memory loss and cognitive impairments in patients with senile dementia. It also promotes proliferation of neural stem cells in the subventricular zone in Parkinson's disease ... The ginkgo biloba extract EGb761 improves memory loss and cognitive impairments in patients with senile dementia. It also promotes proliferation of neural stem cells in the subventricular zone in Parkinson's disease model mice and in the hippocampal zone of young epileptic rats. However, it remains unclear whether EGb761 enhances proliferation of endogenous neural stem cells in the brain of rats with vascular dementia. In this study, a vascular dementia model was established by repeatedly clipping and reperfusing the bilateral common carotid arteries of rats in combination with an intraperitoneal injection of a sodium nitroprusside solution. Seven days after establishing the model, rats were intragastrically given EGb761 at 50 mg/kg per day. Learning and memory abilities were assessed using the Morris water maze and proliferation of endogenous neural stem cells in the subventricular zone and dentate gyrus were labeled by 5-bromo-2-deoxyuridine immunofluorescence in all rats at 15 days, and 1, 2, and 4 months after model establishment. The escape latencies in Morris water maze tests of rats with vascular dementia after EGb761 treatment were significantly shorter than the model group. Immunofluorescence staining showed that the number and proliferation of 5-bromo-2-deoxyuridine-positive cells in the subventricular zone and dentate gyrus of the EGb761-treated group were significantly higher than in the model group. These experimental findings suggest that EGb761 enhances proliferation of neural stem cells in the subventricular zone and dentate gyrus, and significantly improves learning and memory in rats with vascular dementia. 展开更多
关键词 neural regeneration traditional Chinese medicine ginkgo biloba extract EGB761 vasculardementia neural stem cells subventricular zone dentate gyrus learning and memory grants-supported paper NEUROREGENERAtION
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Immunosuppressive effects of rat mesenchymal stem cells:involvement of CD4^+ CD25^+ regulatory T cells 被引量:15
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作者 Ye, Zhou Wang, Yan +1 位作者 Xie, Hai-Yang Zheng, Shu-Sen 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS 2008年第6期608-614,共7页
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... 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-alpha, TGF-beta and 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-alpha) decreased while anti-inflammatory JGF-beta, 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. 展开更多
关键词 mesenchymal stem cells IMMUNOSUPPRESSION regulatory t cells
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High-concentration sevoflurane exposure in mid-gestation induces apoptosis of neural stem cells in rat offspring 被引量:4
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作者 Yuan Wang Shao-Wei Yin +1 位作者 Nan Zhang Ping Zhao 《Neural Regeneration Research》 SCIE CAS CSCD 2018年第9期1575-1584,共10页
Sevoflurane is the most commonly used volatile anesthetic during pregnancy.The viability of neural stem cells directly affects the development of the brain.However,it is unknown whether the use of sevoflurane during t... Sevoflurane is the most commonly used volatile anesthetic during pregnancy.The viability of neural stem cells directly affects the development of the brain.However,it is unknown whether the use of sevoflurane during the second trimester affects the survival of fetal neural stem cells.Therefore,in this study,we investigated whether exposure to sevoflurane in mid-gestation induces apoptosis of neural stem cells and behavioral abnormalities.On gestational day 14,pregnant rats were anesthetized with 2% or 3.5% sevoflurane for 2 hours.The offspring were weaned at 28 days and subjected to the Morris water maze test.The brains were harvested to examine neural stem cell apoptosis by immunofluorescence and to measure Nestin and SOX-2 levels by western blot assay at 6,24 and 48 hours after anesthesia as well as on postnatal day(P) 0,14 and 28.Vascular endothelial growth factor(VEGF) and phosphoinositide 3-kinase(PI3 K)/AKT pathway protein levels in fetal brain at 6 hours after anesthesia were assessed by western blot assay.Exposure to high-concentration(3.5%) sevoflurane during mid-gestation increased escape latency and path length to the platform,and it reduced the average duration spent in the target quadrant and platform crossing times.At 6,24 and 48 hours after anesthesia and at P0,P14 and P28,the percentage of Nestin/terminal deoxynucleotidyl transferase d UTP nick end labeling(TUNEL)-positive cells was increased,but Nestin and SOX-2 protein levels were decreased in the hippocampus of the offspring.At 6 hours after anesthesia,VEGF,PI3 K and phospho-AKT(p-AKT) levels were decreased in the fetal brain.These changes were not observed in animals given low-concentration(2%) sevoflurane exposure.Together,our findings indicate that exposure to a high concentration of sevoflurane(3.5%) in mid-gestation decreases VEGF,PI3 K and p-AKT protein levels and induces neural stem cell apoptosis,thereby causing learning and memory dysfunction in the offspring. 展开更多
关键词 nerve regeneration SEVOFLURANE neural stem cells APOPtOSIS vascular endothelial growth factor PI3K P-AKt ANEStHESIA learning memory developmental neurobiology neural regeneration
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Low-dose intralesional injection of 5-fluorouracil and triamcinolone reduces tissue resident memory T cells in chronic eczema 被引量:4
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作者 Yun Wu Guo-Jiang Wang +6 位作者 Hui-Qiong He Hai-Hong Qin Wen-Tong Shen Yue Yu Xun Zhang Mao-Lin Zhou Jian-Biao Fei 《World Journal of Clinical Cases》 SCIE 2022年第1期166-176,共11页
BACKGROUND Tissue resident memory T(TRM)cells have been reported to play a significant role in the pathogenesis and relapse of chronic eczema.AIM To compare the efficacy and safety of the intralesional injection of 5-... BACKGROUND Tissue resident memory T(TRM)cells have been reported to play a significant role in the pathogenesis and relapse of chronic eczema.AIM To compare the efficacy and safety of the intralesional injection of 5-fluorouracil(5-FU)and triamcinolone(TA)with those associated with TA alone for the treatment of chronic eczema.METHODS A total of 168 patients were randomized to 5-FU+TA or TA groups and received a one-time intralesional injection of 5-FU+TA or TA only.Biopsies were collected before and 2 wk after treatment for evaluation of histopathological changes.All patients were followed up monthly for up to 1 year.RESULTS No serious adverse event was observed in either group.Although the mean atopic dermatitis severity index scores and effective rates were comparable between the two groups after 2 wk of treatment,the relapse rate was significantly lower in the 5-FU+TA group than in the TA group.Histological examination showed significantly fewer CD8^(+)and CD103^(+)T cells but not CD4^(+)T cells in the 5-FU+TA group.CONCLUSION One-time intralesional injection of 5-FU+TA is effective and safe for chronic eczema treatment and can further reduce the retention of T_(RM) cells in the lesional skin and the relapse rate of chronic eczema. 展开更多
关键词 Chronic eczema 5-FLUOROURACIL tRIAMCINOLONE Intralesional injection tissue resident memory t cell
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Differences and similarities between mesenchymal stem cell and endothelial progenitor cell immunoregulatory properties against T cells 被引量:2
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作者 Mehdi Razazian Maryam Khosravi +3 位作者 Sheyda Bahiraii Georges Uzan Sara Shamdani Sina Naserian 《World Journal of Stem Cells》 SCIE 2021年第8期971-984,共14页
Bone-marrow-derived mesenchymal stem cells and endothelial progenitor cells have some interesting biological properties that make them unique for cell therapy of degenerative and cardiovascular disorders.Although both... Bone-marrow-derived mesenchymal stem cells and endothelial progenitor cells have some interesting biological properties that make them unique for cell therapy of degenerative and cardiovascular disorders.Although both cell populations have been already studied and used for their regenerative potentials,recently their special immunoregulatory features have brought much more attention.Mesenchymal stem cells and endothelial progenitor cells have both proangiogenic functions and have been shown to suppress the immune response,particularly T cell proliferation,activation,and cytokine production.This makes them suitable choices for allogeneic stem cell transplantation.Nevertheless,these two cells do not have equal immunoregulatory activities.Many elements including their extraction sources,age/passage,expression of different markers,secretion of bioactive mediators,and some others could change the efficiency of their immunosuppressive function.However,to our knowledge,no publication has yet compared mesenchymal stem cells and endothelial progenitor cells for their immunological interaction with T cells.This review aims to specifically compare the immunoregulatory effect of these two populations including their T cell suppression,deactivation,cytokine production,and regulatory T cells induction capacities.Moreover,it evaluates the implications of the tumor necrosis factor alpha-tumor necrosis factor receptor 2 axis as an emerging immune checkpoint signaling pathway controlling most of their immunological properties. 展开更多
关键词 Endothelial Progenitor cells Mesenchymal stem cells t cells IMMUNOSUPPRESSION IMMUNOREGULAtION tNFα-tNFR2 signaling pathway
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Mucosal-associated invariant T cells from induced pluripotent stem cells:A novel approach for modeling human diseases 被引量:2
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作者 Chie Sugimoto Hiroyoshi Fujita Hiroshi Wakao 《World Journal of Stem Cells》 SCIE CAS 2016年第4期158-169,共12页
Mice have frequently been used to model human diseases involving immune dysregulation such as autoimmune and inflammatory diseases.These models help elucidatethe mechanisms underlying the disease and in the developmen... Mice have frequently been used to model human diseases involving immune dysregulation such as autoimmune and inflammatory diseases.These models help elucidatethe mechanisms underlying the disease and in the development of novel therapies.However,if mice are deficient in certain cells and/or effectors associated with human diseases,how can their functions be investigated in this species?Mucosal-associated invariant T(MAIT)cells,a novel innate-like T cell family member,are a good example.MAIT cells are abundant in humans but scarce in laboratory mice.MAIT cells harbor an invariant T cell receptor and recognize nonpeptidic antigens vitamin B2metabolites from bacteria and yeasts.Recent studies have shown that MAIT cells play a pivotal role in human diseases such as bacterial infections and autoimmune and inflammatory diseases.MAIT cells possess granulysin,a human-specific effector molecule,but granulysin and its homologue are absent in mice.Furthermore,MAIT cells show poor proliferation in vitro.To overcome these problems and further our knowledge of MAIT cells,we have established a method to expand MAIT cells via induced pluripotent stem cells(iP SCs).In this review,we describe recent advances in the field of MAIT cell research and our approach for human disease modeling with iP SCderived MAIT cells. 展开更多
关键词 Mucosal-associated invariant t cells Induced pluripotent stem cells DIFFERENtIAtION Adoptive transfer Inflammatory diseases Autoimmune diseases Disease modeling Infectious diseases Immunocompromised mouse
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Cytotoxic CD8+ T cells and tissue resident memory cells in colorectal cancer based on microsatellite instability and BRAF status 被引量:2
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作者 James Wei Tatt Toh Angela L Ferguson +2 位作者 Kevin J Spring Hema Mahajan Umaimainthan Palendira 《World Journal of Clinical Oncology》 CAS 2021年第4期238-248,共11页
BACKGROUND Recent studies in non-colorectal malignancy have associated T resident memory(T_(RM)) cells with improved patient survival. It is unknown if T_(RM) plays a role in colorectal cancer(CRC).AIM To examine the ... BACKGROUND Recent studies in non-colorectal malignancy have associated T resident memory(T_(RM)) cells with improved patient survival. It is unknown if T_(RM) plays a role in colorectal cancer(CRC).AIM To examine the potential role of T_(RM) cells in providing immunogenicity in CRC stratified by microsatellite instability(MSI) and BRAF status.METHODS Patients with known MSI and BRAF mutation status were eligible for inclusion in this study. CRC tumour sections stained with haematoxylin and eosin were microscopically reviewed and the images scanned prior to assessment for location of invading edge and core of tumour. Sequential sections were prepared for quantitative multiplex immunohistochemistry(IHC) staining. Opal Multiplex IHC staining was performed with appropriate positive and negative controls and imaged using a standard fluorescent microscope fitted with a spectral scanning camera(Mantra) in conjunction with Mantra snap software. Images were unmixed and annotated in in Form 2.2.0. Statistical analysis was performed using Graphpad Prism Version 7 and Stata Version 15.RESULTS Seventy-two patients with known MSI and BRAF status were included in the study. All patients were assessed for MSI by IHC and high resolution capillary electrophoresis testing and 44 of these patients successfully underwent quantitative multiplex IHC staining. Overall, there was a statistically significant increase in CD8+ T_(RM) cells in the MSI(BRAF mutant and wild type) group over the microsatellite stable(MSS) group. There was a statistically significant difference in CD8+ T_(RM) between high level MSI(MSI-H):BRAF mutant [22.57, 95% confidence interval(CI): 14.31-30.84] vs MSS [8.031(95%CI: 4.698-11.36)], P = 0.0076 and MSI-H:BRAF wild type [16.18(95%CI: 10.44-21.93)] vs MSS [8.031(95%CI: 4.698-11.36)], P = 0.0279. There was no statistically significant difference in CD8 T cells(both CD8+CD103-and CD8+CD103+T_(RM)) between MSI-H: BRAF mutant and wild type CRC.CONCLUSION This study has shown that CD8+ T_(RM) are found in greater abundance in MSI-H CRC, both BRAF mutant and MSI-H:BRAF wild type, when compared with their MSS counterpart. CD8+ T_(RM) may play a role in the immunogenicity in MSI-H CRC(BRAF mutant and BRAF wild type). Further studies should focus on the potential immunogenic qualities of T_(RM) cells and investigate potential immunotherapeutic approaches to improve treatment and survival associated with CRC. 展开更多
关键词 tissue resident memory cells Resident memory t cells Colorectal cancer Microsatellite instability BRAF DNA mismatch repair IMMUNOtHERAPY Prognosis
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Impact of T cells on hematopoietic stem and progenitor cell function:Good guys or bad guys?
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作者 Sulima Geerman Martijn A Nolte 《World Journal of Stem Cells》 SCIE CAS 2017年第2期37-44,共8页
When hematopoietic stem and progenitor cells(HSPC)are harvested for transplantation, either from the bone marrow or from mobilized blood, the graft contains a significant number of T cells. It is these T cells that ar... When hematopoietic stem and progenitor cells(HSPC)are harvested for transplantation, either from the bone marrow or from mobilized blood, the graft contains a significant number of T cells. It is these T cells that are the major drivers of graft-vs-host disease(Gv HD). The risk for Gv HD can simply be reduced by the removal of these T cells from the graft. However, this is not always desirable, as this procedure also decreases the engraftment of the transplanted HSPCs and, if applicable, a graft-vs-tumor effect. This poses an important conundrum in the field: T cells act as a double-edged sword upon allogeneic HSPC transplantation, as they support engraftment of HSPCs and provide anti-tumor activity, but can also cause Gv HD. It has recently been suggested that T cells also enhance the engraftment of autologous HSPCs, thus supporting the notion that T cells and HSPCs have an important functional interaction that is highly beneficial, in particular during transplantation. The underlying reason on why and how T cells contribute to HSPC engraftment is still poorly understood. Therefore, we evaluate in this review the studies that have examined the role of T cells during HSPC transplantation and the possible mechanisms involved in their supporting function. Understanding the underlying cellular and molecular mechanisms can provide new insight into improving HSPC engraftment and thus lower the number of HSPCs required during transplantation. Moreover, it could provide new avenues to limit the development of severe Gv HD, thus making HSPC transplantations more efficient and ultimately safer. 展开更多
关键词 HEMAtOPOIEtIC stem cells HEMAtOPOIEtIC stem and PROGENItOR cells CD8 t cells transplantation ENGRAFtMENt memory t cells Facilitating cells Bone MARROW
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Human adipose, placenta, and umbilical cord-derived mesenchymal stem cells ameliorate imiquimod-induced psoriatic mice via reducing T cells infiltration
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作者 JIGANG LEI ZHENYAO XU +9 位作者 SUKE LI MENG LI ZHIKAI WANG PING LI JING WANG YINGLU CHEN X IAOLE SONG CHENGJIE REN MEIPING SHEN CHENGXIANG DAI 《BIOCELL》 SCIE 2021年第3期537-546,共10页
Psoriasis is an autoimmune-related chronic inflammatory disease with an approximate prevalence of 2–3%around the world,involving increased keratinocyte proliferation.Indeed,Th17 cells and IL-17 play critical roles in... Psoriasis is an autoimmune-related chronic inflammatory disease with an approximate prevalence of 2–3%around the world,involving increased keratinocyte proliferation.Indeed,Th17 cells and IL-17 play critical roles in the pathogenesis of psoriasis.The monoclonal antibodies against cytokines have been shown to have effectively immunosuppressive effects on human psoriasis.However,there are still some patients that have no response to these treatments.Some patients have even serious side-effects which may affect their life.Mesenchymal stem cells have the ability of immunosuppressive and anti-inflammatory effects,which may be an alternative therapy with more safety and efficacy for human psoriasis.Moreover,the underlying mechanisms by which the MSCs prevent or ameliorate psoriasis are still poorly understood.Here,we first isolated and characterized human adipose,placenta,and umbilical cord-derived mesenchymal stem cells(haMSCs,hpMSCs,and huMSCs).After that,the animal model of imiquimod(IMQ)-induced psoriasis in C57BL/6 mice was confirmed.We investigated the impact of haMSCs,hpMSCs,and huMSCs on this model by H&E staining,immunohistochemistry staining,and quantitative real-time PCR.Data analysis showed that mice subcutaneously injected with these MSCs had a significantly decreased epidermal thickness,which was caused by obviously reduced hyper-proliferation of keratinocytes.Furthermore,our findings revealed that the infiltration of T cells to psoriatic lesions in IMQ-induced psoriasis mice was markedly downregulated by intradermal administration of haMSCs,hpMSCs,and huMSCs,respectively.Consequently,the production of IL-17 from Th17 cells was reduced,which inhibits the proliferation of keratinocytes in lesioned skin of IMQ-induced psoriasis mice.These data suggest that haMSCs,hpMSCs,and huMSCs can inhibit the effects of proinflammatory Th17 cells on the development of psoriasis,which may be potential therapeutic candidates for skin inflammatory disease or other autoimmune diseases. 展开更多
关键词 Mesenchymal stem cells PSORIASIS t cells Skin inflammation cell therapy
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