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Rapamycin ameliorates experimental autoimmune uveoretinitis by inhibiting th1/th2/th17 cells and upregulating CD4+CD25+ Foxp3 regulatory T cells

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International Journal of Ophthalmology(English edition) 2015年第4期8卷 659-664页

作者： Li-Fei Yuan Guang-Da Li Xin-Jun Ren Hong Nian Xiao-Rong Li Xiao-Min Zhang Tianjin Medical University Eye Hospital & Eye Institute Hebei Eye Hospital Linyi People's Hospital

· 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 *** 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 *** is a promising new alternative as an adjunct corticosteroid-sparing agent for treating uveitis.

关键词： experimental autoimmune uveoretinitis rapamycin regulatory T cells th1 cells th2 cells th17 cells uveitis

Relationship between th17 cells and allograft rejection

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Frontiers of Medicine 2009年第4期3卷 491-494页

作者： Zhikun ZHENG Jinsong LI Ke JIANG Department of thoracic Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China

th17 cells,a special kind of auxiliary type T cells,can secrete IL-17A,IL-17F,IL-21,IL-22,etc.,as a newly discovered T-cell subset in recent *** a different subset from the th1 and th2 cells,th17 cells play an important role in the development of a variety of autoimmune diseases.A current study shows that the IL-6 inﬂammatory response of the organization in combination with the occurrence of TGF-β can induce the differentia-tion of th17 ***-23 can promote the production of IL17,as well as participate in ampliﬁcation and main-tenance of the survival of IL-17 generating *** this process,STAT3 and ROR-γt are key transcription factors for the growing of th17 *** our knowledge of th17 family members is rapidly growing and changing,it will be important to specify their involvement in the induction and regulation of allograft rejection in animal models as well as in clinical ***,we review the key features of th17 cells and discuss their potential relevance to transplantation immunity.

关键词： th17 cells regulation allograft rejection

th17 cells and Tregs in HTLV-1 Infection

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Journal of Clinical and Nursing Research 2022年第3期6卷 122-127页

作者： Nafiseh Saghafi Elham Abdollahi Malihe Hasanzadeh Mofrad Department of Gynecology and Obstetrics Mashhad University of Medical SciencesMashhadIran Immunology Research Center Inflammation and Inflammatory Disease Research Centre Mashhad University of Medical SciencesMashhadIran

HTLV-1(human T-lymphotropic virus type 1)causes chronic infection ofhuman T ***-1 infection is known to be related to multiple diseases,including neoplastic growth of HTLV-1-infected T cells(ATL)and neoplastic inflammatory conditions,such as HTLV-1-associated myelopathy/tropical spastic paraparesis(HAM/TSP),Sjogren's syndrome with arthritis,polymyositis uveitis,and *** T cells(Tregs)regulate inflammatory cells,such as th17 *** purpose of this study was to evaluate Tregs and th17 cells,as well as the expression of related transcription factors(ROR-γ1 and FOXP3)and cytokines(IL-10,TGF-β,IL-6,and IL-17A)in HTLV-1 infection.

关键词： Tregs th17 cells HTLV-1,HAMP/TSP

p38 MAPK plays a role in the GITRL promoting th17 cells differentiation and involves pathogenesis of murine collageninduced arthritis

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p38 MAPK plays a role in the GITRL promoting TH17 cells diff...

第十届全国免疫学学术大会

作者： Xinyi Tang Shengjun Wang Department of Laboratory Medicine Affiliated People’s Hospital Jiangsu University

Background:the natural ligand of glucocorticoid-induced tumor necrosis factor receptor(GITRL)could exacerbate autoimmune arthritis via the enhancement of th17 cells *** purpose of this study is to investigate the role of p38 signaling during the enhancement of th17 expansion and exacerbation of autoimmune arthritis by GITRL ***:We used m GITRL as a co-stimulatory factor for th17 differentiation in presence or absence of p38 inhibitor and detected ability of th17 *** nave CD4+T cells were pretreated with or without p38 inhibitor before stimulated with m GITRL and phosphorylation of p38 and STAT3 were examined by western *** we injected m GITRL protein into collagen induced arthritis(CIA)mice alone or combine with the p38 ***:In this study,nave CD4+T cells could differentiate into higher frequency of th17 cells under the m GITRL costimulated and be attenuated in a concentration dependent manner by p38 inhibitor ***,the relative expression of RORγt and IL-17 m RNA was impaired with p38 inhibitor in a concentration dependent *** of p38 was reinforced in activated nave CD4+T cells after stimulated with GITRL *** enhancement of STAT3Ser727 phosphorylation by m GITRL stimulate was observed and been attenuated in activated nave CD4+T cells with p38inhibitor *** with the group treated by m GITRL protein(m GITRL-CIA group),the group injected with m GITRL and p38 inhibitor(m GITRL-SB203580-CIA group)had a later onset of symptoms and reached the peak score ***17 cells in the m GITRL-group increased significantly compared with the m GITRL-SB203580-CIA ***,there is a significantly higher of phosphorylation level of p38 MAPK in peripheral CD4+T cells of RA patients than in healthy control ***:Our results suggested that the enhancement of th17 cells differentiation with m GITRL stimulation was in-fluenced by p38-STAT3 signaling pathway

关键词： p38 MAPK GITRL th17 cells collagen-induced arthritis

IL-17A,but not IL-17F,is indispensable for airway vascular remodeling induced by exaggerated th17 cells in prolonged ovalbumin-challenged mice

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IL-17A,but not IL-17F,is indispensable for airway vascular r...

第九届全国免疫学学术大会

作者： ShanLu HequanLi RundiGao XuanGao FeiXu QingWang GuohuaLu DajingXia JianyingZhou Department of Respiratory and Critical Care Medicine First Affiliated Hospital of Zhejiang University School of Medicine Zhejiang University Department of Respiratory Diseases First Affiliated Hospital of Zhejiang Chinese Medicine University School of Public Health Zhejiang University

Rationale and Objective:Our previous study has depicted an essential role of th17 cells in excessive mucus secretion and airway smooth muscle proliferation in a prolonged ovalbumin(OVA)-challenged C57BL/6 mouse ***,the impact of th17 cells against vascular remodeling,another characteristic features of airway remodeling in asthma,remains *** this paper,we made further study to explore this ***:An asthmatic airway remodeling murine model was established by prolonged OVA exposure in sensitized C57BL/6 *** effect of th17 cell and its cytokines on vascular remodeling,mobilization and recruitment of endothelial progenitor cells(EPCs),proliferation and tubule formation of pulmonary microvascular endothelia cells(PMVECs)were ***:the time-course experiments showed that progressively increasing levels of th17 cells and IL-17A(not IL-17F)in the lungs of prolonged allergen-challenged mice were positively correlated with microvessel density(MVD)in perbronchial *** exaggerated airway vascular remodeling in such mouse model was aggravated by instillation of IL-17A or adoptive transfer of th17,which dramatically ameliorated by anti-IL-17A antibody,but not anti-IL-17F antibody,***,Boyden chamber assay exhibited that IL-17A might accelerate EPCs ***,EPCs accumulation in the airway of allergen exposure mice resulted from adoptive transfer of th17 can be eliminated by blockade of ***,we found that IL-17A promoted tubule-like formation rather than proliferation of PMVECs in ***:Collectively,our results raise the possibility that th17 cells might contributes to the airway vascular remodeling by mediating EPCs chemotaxis as well as PMVECs tube formation via IL-17A rather than IL-17F in asthma.

关键词： th17 cells IL-17A Airway vascular remodeling Asthma

the th17 and Treg cells and its role in gout arthritis

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The Th17 and Treg cells and its role in gout arthritis

第十一届全国免疫学学术大会

作者： Zhong Xiaowu Yang Hong Qing Yufeng Xie Wenguang Zhou Jingguo Medicine Research Center the Affiliated Hospital of North Sichuan Medical College Institute of Rheumatology and Immunology North Sichuan Medical College Department of Rheumatology and Immunology of the Affiliated Hospital North Sichuan Medical College

Objective:To investigate the possible role of th17/Treg cells in gout arthritis(GA). Methods: the PBMCs of 32 acute gout patients(AG), 34 interval gout patients(IG) and 26 healthy controls(HC) were collected. the clinical data and laboratory of them were enrolled. the percentages of th17 and Treg cells were detected by flow cytometry. the expression of Foxp3 and ROR-γt mRNA in PBMCs were measured using RT-qPCR. SPSS21.0 was used for analysis. the measurement data were compared by one factor analysis of variance test. the correlation between variables was used by Spearman correlation analysis. Results: the percentage of th17 cells in PBMCs of AG group was(2.85%±0.92%) was significantly increased(Pth that in IG group(1.34%±0.67%) and HC group(1.25%±0.52%). However, there was no significant difference between IG and HC group(P>0.05). the proportion of Treg cells in the PBMCs of AG and IG group were(3.39±1.37)%, which was significantly lower(Pthan HC group(5.58±1.83). there was no significant difference between IG and AG group(P>0.05). the proportion of th17/Treg cells in AG group was higher than IG and HC group. Compared with HC group, the expression of ROR-γt mRNA in AG and IG group were higher(Pthere was no significant difference between IG and AG group(P>0.05). the expression of Foxp3 mRNA were significantly lower(Pthere was no significant difference between AG and IG group(P>0.05). the correlation analysis found the correlation of ROR-γt and Foxp3 mRNA expression levels in AG was positive correlation(r = 1.000, Pth17 cells percentage was foundcorrelate significantly with AST in GA patients(r=-0.361, Pth17/Treg balance in GA patients may have an important role in the pathogenesis of GA.

关键词： Gouty arthritis th17 cells Treg cells Foxp3 ROR-γt

Roles of th17 and Treg cells in Neuroinflammation and Neurodegeneration in a Mouse Model of Parkinson's Disease

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Roles of Th17 and Treg Cells in Neuroinflammation and Neurod...

中国神经科学学会第十二届全国学术会议

作者： Yu-Ping PENG Zhan LIU Yan HUANG Jin-Na CHEN Yi-Hua QIU Department of Physiology School of Medicine Nantong University

Objective Helper T(th)17 cells and regulatory T(Treg) cells are two new members in CD4 T lymphocytes and they play pro-inflammatory and anti-inflammatory roles, respectively, in immune response. th17/Treg imbalance has been associated with autoimmune diseases. Parkinson’s disease(PD), a neurodegenerative disease, has been related to neuroinflammation induced by microglia. However, the involvement of T lymphocytes in PD is less clear. Herein, we aimed to reveal roles and mechanisms of th17 and Treg cells in PD neuroiflammation and neurodegeneration. Methods PD mouse model was prepared by intraperitoneal injection of MPTP. IL-17 A-deficient PD mice and adoptive transfer of Treg cells to PD mice were used to evaluate effects of th17 cells and Treg cells on PD, respectively. Live cell imaging system was employed to observe a dynamic contact of th17 cells or Treg cells with neurons. Results In the substantia nigra of PD model mice, blood-brain barrier was disrupted, and th17 cell number increased but Treg cells decreased. the th17-related pro-inflammatory cytokines and inflammatory mediators, IL-17, IL-22, TNF-α, IL-1β and i NOS, were upregulated, while the Tregrelated anti-inflammatory cytokines and neurotrophic factors, TGF-β, IL-10, GDNF, BDNF and IGF-1, were downregulated in ventral midbrain of PD mice. Either IL-17 A deficiency or Treg cell transfer alleviated MPTP-induced PD-like changes. In primary ventral mesencephalic cell cultures, th17 cells exacerbated but Treg cells alleviated MPP+-induced neuroinflammation and neurotoxicity. the effects of both the T cells on neurons were implemented by interaction between membrane surface molecules. However, cytokines from the T cells needed microglial mediation to exert neurotoxicity or neuroprotection, as neurons did not express receptors of the cytokines. Conclusions th17/Treg imbalance appears in PD brain. Both th17 and Treg cells can directly act on neurons to exert neurotoxicity and neuroprotection, respectively. But

关键词： th17 cells Treg cells neuroinflammation neurodegeneration Parkinson’s disease

the expression of th17/Treg cells in skin lesions during leprosy,and its clinical significance

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The expression of Th17/Treg cells in skin lesions during lep...

2019年全国麻风皮肤病学术年会

作者： JIAN WANG GUOCHENG ZHANG QIANG YAO HUILIANG SHEN XIAOBING YU QIAN CHEN HAO CHENG Department of Dermatology Sir Run Run Shaw HospitalSchool of MedicineZhejiang University Zhejiang Provincial Institute of Dermatology Institute of Dermatology and Hospital for Skin Diseases Chinese Academy of Medical Sciences

Background:T helper 17(th17) cells and regulatory T cells(Tregs) are derived from naive CD4 *** remains contentious as to whether the balance between th17 and Tregs is disturbed in leprosy *** this study,the expression of transcription factors and cytokines was examined in th17 and Tregs from skin lesions of leprosy patients,in order to further investigate the potential role of TGF-b,RORgt,IL-10,IL-17,and FOXP3 in the pathogenesis of ***:Sixty leprosy patients and twenty healthy subjects,matched for age and gender,were *** staining was carried out,and the results were analysed using a semi-quantitative scoring ***:the expression of RORgt was increased in borderline lepromatous leprosy(BL),borderline tuberculoid leprosy(BT),and tuberculoid leprosy(TT) ***,RORgt expression was lower in lepromatous leprosy(LL) than in other types of ***,there was no significant difference in the expression of IL-17 between leprosy groups and healthy *** expression of FOXP3 was significantly increased in all types of leprosy when compared with healthy *** expression of IL-10 was increased in BL,LL and TT groups,but was lower in the BT group than in other types of leprosy(Pthe expression of TGF-b was markedly increased in BL,BT,and LL groups(Pthe transcription factors and cytokines in th17 and Tregs may be involved in the pathogenesis of leprosy and further research could provide a novel therapeutic target for leprosy.

关键词： Leprosy th17 cells Tregs Transcription factor Cytokine Immunohistochemistry

Identification and functional characterization of fish IL‑17 receptors suggest important roles in the response to nodavirus infection

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Marine Life Science & Technology 2024年第2期6卷 252-265页

作者： Carmen González‑Fernández Miguel A.García‑Álvarez Alberto Cuesta Department of Cell Biology and Histology Faculty of BiologyUniversity of Murcia30100 MurciaSpain Laboratoire d’écotoxicologie Centre de Lyon-VilleurbanneINRAEUR RiverLy69625 VilleurbanneFrance

th17 is a lymphocyte T helper(th)subpopulation relevant in the control and regulation of the immune response characterized by the production of interleukin(IL)-*** crucial cytokine family acts through their binding to the IL-17 receptors(IL-17R),having up to six *** the biology of fish th17 is well-recognized,the molecular and functional characterization of IL-17 and IL-17R has been ***,our aim was to identify and characterize the IL-17R repertory and regulation in the two main Mediterranean cultured fish species,the gilthead seabream(Sparus aurata)and the European sea bass(Dicentrarchus labrax).Our in silico results showed the clear identification of six members in each fish species,from IL-17RA to IL-17RE-like,with well-conserved gene structure and protein domains with their human *** of them showed wide and constitutive transcription in naïve tissues but with highest levels in mucosal tissues,namely skin,gill or *** leucocytes,T mitogens showed the strongest up-regulation in most of the il17 receptors though il17ra resulted in inhibition by most ***,in vivo nodavirus infection resulted in alterations on the transcription of il17 *** nodavirus infection led to some increments in the il17ra,il17rb,il17rc and il17rd transcripts in the susceptible European sea bass,many down-regulations were observed in the resistant gilthead *** data identify the presence and conservation of six coding IL-17R in gilthead seabream and European sea bass as well as their differential regulation in vitro and upon nodavirus infection.

关键词： th17 cells IL-17 receptors Immunity Teleost fish Nodavirus(NNV) Aquaculture