多克隆 CD4+Foxp3+Treg 细胞诱导 TGFβ 依赖性致耐受树突状细胞，从而抑制狼疮样综合征。
Polyclonal CD4+Foxp3+ Treg cells induce TGFβ-dependent tolerogenic dendritic cells that suppress the murine lupus-like syndrome.
机构信息
Division of Rheumatology and Immunology, Department of Medicine, Keck School of Medicine at University of Southern California, 2011 Zonal Avenue, HMR710, Los Angeles, CA 90033, USA.
出版信息
J Mol Cell Biol. 2012 Dec;4(6):409-19. doi: 10.1093/jmcb/mjs040. Epub 2012 Jul 6.
Abstract
Interplay between Foxp3(+) regulatory T cells (Treg) and dendritic cells (DCs) maintains immunologic tolerance, but the effects of each cell on the other are not well understood. We report that polyclonal CD4(+)Foxp3(+) Treg cells induced ex vivo with transforming growth factor beta (TGFβ) (iTreg) suppress a lupus-like chronic graft-versus-host disease by preventing the expansion of immunogenic DCs and inducing protective DCs that generate additional recipient CD4(+)Foxp3(+) cells. The protective effects of the transferred iTreg cells required both interleukin (IL)-10 and TGFβ, but the tolerogenic effects of the iTreg on DCs, and the immunosuppressive effects of these DCs were exclusively TGFβ-dependent. The iTreg were unable to tolerize Tgfbr2-deficient DCs. These results support the essential role of DCs in 'infectious tolerance' and emphasize the central role of TGFβ in protective iTreg/DC interactions in vivo.
摘要
Foxp3(+) 调节性 T 细胞 (Treg) 和树突状细胞 (DC) 之间的相互作用维持着免疫耐受，但对于彼此的影响还不是很清楚。我们报告说，用转化生长因子 β (TGFβ) 体外诱导的多克隆 CD4(+)Foxp3(+)Treg 细胞 (iTreg) 通过防止免疫原性 DC 的扩增和诱导产生额外的受体 CD4(+)Foxp3(+)细胞的保护性 DC 来抑制狼疮样慢性移植物抗宿主病。转移的 iTreg 细胞的保护作用需要白细胞介素 (IL)-10 和 TGFβ，但 iTreg 对 DC 的耐受作用，以及这些 DC 的免疫抑制作用仅依赖于 TGFβ。iTreg 不能耐受 Tgfbr2 缺陷型 DC。这些结果支持了 DC 在“感染性耐受”中的重要作用，并强调了 TGFβ 在体内保护性 iTreg/DC 相互作用中的核心作用。
相似文献
1
Polyclonal CD4+Foxp3+ Treg cells induce TGFβ-dependent tolerogenic dendritic cells that suppress the murine lupus-like syndrome.多克隆 CD4+Foxp3+Treg 细胞诱导 TGFβ 依赖性致耐受树突状细胞，从而抑制狼疮样综合征。
J Mol Cell Biol. 2012 Dec;4(6):409-19. doi: 10.1093/jmcb/mjs040. Epub 2012 Jul 6.
2
Selective expansion of foxp3-positive regulatory T cells and immunosuppression by suppressors of cytokine signaling 3-deficient dendritic cells.细胞因子信号传导抑制因子3缺陷的树突状细胞对foxp3阳性调节性T细胞的选择性扩增及免疫抑制作用
J Immunol. 2007 Aug 15;179(4):2170-9. doi: 10.4049/jimmunol.179.4.2170.
3
Dominant role of antigen dose in CD4+Foxp3+ regulatory T cell induction and expansion.抗原剂量在CD4+Foxp3+调节性T细胞诱导和扩增中的主导作用。
J Immunol. 2009 Oct 15;183(8):4895-903. doi: 10.4049/jimmunol.0901459.
4
Transforming growth factor-beta/transforming growth factor-betaRII signaling may regulate CD4+CD25+ T-regulatory cell homeostasis and suppressor function in feline AIDS lentivirus infection.转化生长因子-β/转化生长因子-β受体II信号传导可能调节猫艾滋病慢病毒感染中CD4+CD25+调节性T细胞的稳态和抑制功能。
J Acquir Immune Defic Syndr. 2008 Feb 1;47(2):148-60. doi: 10.1097/QAI.0b013e318160df70.
5
Tolerogenic dendritic cells induced the enrichment of CD4Foxp3 regulatory T cells via TGF-β in mesenteric lymph nodes of murine LPS-induced tolerance model.诱导耐受的树突状细胞通过 TGF-β在 LPS 诱导的耐受模型的肠系膜淋巴结中诱导 CD4Foxp3 调节性 T 细胞的富集。
Clin Immunol. 2018 Dec;197:118-129. doi: 10.1016/j.clim.2018.09.010. Epub 2018 Sep 21.
6
Dendritic cell-specific disruption of TGF-β receptor II leads to altered regulatory T cell phenotype and spontaneous multiorgan autoimmunity.树突状细胞特异性敲除 TGF-β 受体 II 导致调节性 T 细胞表型改变和自发性多器官自身免疫。
J Immunol. 2012 Oct 15;189(8):3878-93. doi: 10.4049/jimmunol.1201029. Epub 2012 Sep 12.
7
Autoimmune pancreatitis results from loss of TGFbeta signalling in S100A4-positive dendritic cells.自身免疫性胰腺炎是由S100A4阳性树突状细胞中转化生长因子β信号通路缺失所致。
Gut. 2009 Sep;58(9):1267-74. doi: 10.1136/gut.2008.170779. Epub 2009 Jul 21.
8
Tolerogenic splenic IDO (+) dendritic cells from the mice treated with induced-Treg cells suppress collagen-induced arthritis.诱导性调节性 T 细胞治疗后的耐受性脾 IDO(+)树突状细胞可抑制胶原诱导性关节炎。
J Immunol Res. 2014;2014:831054. doi: 10.1155/2014/831054. Epub 2014 Oct 27.
9
Antigen-specific transforming growth factor β-induced Treg cells, but not natural Treg cells, ameliorate autoimmune arthritis in mice by shifting the Th17/Treg cell balance from Th17 predominance to Treg cell predominance.抗原特异性转化生长因子β诱导的调节性T细胞而非天然调节性T细胞，通过将辅助性T细胞17/调节性T细胞平衡从以辅助性T细胞17为主转变为以调节性T细胞为主，改善小鼠自身免疫性关节炎。
Arthritis Rheum. 2012 Aug;64(8):2548-58. doi: 10.1002/art.34513.
10
Glucocorticoid hormone differentially modulates the in vitro expansion and cytokine profile of thymic and splenic Treg cells.糖皮质激素激素可差异调节胸腺和脾脏 Treg 细胞的体外扩增和细胞因子谱。
Immunobiology. 2019 Mar;224(2):285-295. doi: 10.1016/j.imbio.2018.12.002. Epub 2018 Dec 27.
引用本文的文献
1
PD-L1 in plasmacytoid dendritic cells promote HBV persistence through disrupting humoral immune response.浆细胞样树突状细胞中的程序性死亡配体1通过破坏体液免疫反应促进乙肝病毒持续感染。
Front Immunol. 2025 Apr 24;16:1545667. doi: 10.3389/fimmu.2025.1545667. eCollection 2025.
2
Exploring the predictive values of CRP and lymphocytes in coronary artery disease based on a machine learning and Mendelian randomization.基于机器学习和孟德尔随机化探索C反应蛋白和淋巴细胞在冠状动脉疾病中的预测价值。
Front Cardiovasc Med. 2024 Sep 9;11:1442275. doi: 10.3389/fcvm.2024.1442275. eCollection 2024.
3
Nanoparticles loaded with IL-2 and TGF-β promote transplantation tolerance to alloantigen.载有白细胞介素 2 和转化生长因子-β的纳米颗粒促进同种抗原移植耐受。
Front Immunol. 2024 Jul 26;15:1429335. doi: 10.3389/fimmu.2024.1429335. eCollection 2024.
4
Gingival-derived mesenchymal stem cells alleviate allergic asthma inflammation via HGF in animal models.牙龈来源的间充质干细胞在动物模型中通过肝细胞生长因子减轻过敏性哮喘炎症。
iScience. 2024 Apr 26;27(5):109818. doi: 10.1016/j.isci.2024.109818. eCollection 2024 May 17.
5
CAR-T cells and CAR-Tregs targeting conventional type-1 dendritic cell suppress experimental autoimmune encephalomyelitis.嵌合抗原受体 T 细胞和嵌合抗原受体调节性 T 细胞靶向传统的 1 型树突状细胞可抑制实验性自身免疫性脑脊髓炎。
Front Immunol. 2023 Oct 27;14:1235222. doi: 10.3389/fimmu.2023.1235222. eCollection 2023.
6
Expression Signature of Immune-Related MicroRNAs in Autoimmune Skin Disease: Psoriasis and Vitiligo Insights.自身免疫性皮肤病中免疫相关 microRNAs 的表达特征：银屑病和白癜风的见解。
Mol Diagn Ther. 2023 May;27(3):405-423. doi: 10.1007/s40291-023-00646-1. Epub 2023 Apr 4.
7
Extracellular vesicles and their cells of origin: Open issues in autoimmune diseases.细胞外囊泡及其来源细胞：自身免疫性疾病中的未解决问题。
Front Immunol. 2023 Mar 8;14:1090416. doi: 10.3389/fimmu.2023.1090416. eCollection 2023.
8
Vitamin D Metabolism and Its Role in Temporomandibular Joint Osteoarthritis and Autoimmune Thyroid Diseases.维生素 D 代谢及其在颞下颌关节骨关节炎和自身免疫性甲状腺疾病中的作用。
Int J Mol Sci. 2023 Feb 17;24(4):4080. doi: 10.3390/ijms24044080.
9
Regulatory B cells improve ventricular remodeling after myocardial infarction by modulating monocyte migration.调节性 B 细胞通过调节单核细胞迁移改善心肌梗死后的心室重构。
Basic Res Cardiol. 2021 Jul 24;116(1):46. doi: 10.1007/s00395-021-00886-4.
10
Emerging Therapeutics for Immune Tolerance: Tolerogenic Vaccines, T cell Therapy, and IL-2 Therapy.免疫耐受的新兴治疗策略：耐受原疫苗、T 细胞治疗和 IL-2 治疗。
Front Immunol. 2021 Mar 29;12:657768. doi: 10.3389/fimmu.2021.657768. eCollection 2021.
本文引用的文献
1
Induced CD4+ forkhead box protein-positive T cells inhibit mast cell function and established contact hypersensitivity through TGF-β1.诱导型 CD4+ forkhead box protein 阳性 T 细胞通过 TGF-β1 抑制肥大细胞功能并建立接触性超敏反应。
J Allergy Clin Immunol. 2012 Aug;130(2):444-52.e7. doi: 10.1016/j.jaci.2012.05.011. Epub 2012 Jun 26.
2
Antigen-specific transforming growth factor β-induced Treg cells, but not natural Treg cells, ameliorate autoimmune arthritis in mice by shifting the Th17/Treg cell balance from Th17 predominance to Treg cell predominance.抗原特异性转化生长因子β诱导的调节性T细胞而非天然调节性T细胞，通过将辅助性T细胞17/调节性T细胞平衡从以辅助性T细胞17为主转变为以调节性T细胞为主，改善小鼠自身免疫性关节炎。
Arthritis Rheum. 2012 Aug;64(8):2548-58. doi: 10.1002/art.34513.
3
Induced Foxp3(+) regulatory T cells: a potential new weapon to treat autoimmune and inflammatory diseases?诱导 Foxp3(+) 调节性 T 细胞：治疗自身免疫和炎症性疾病的潜在新武器？
J Mol Cell Biol. 2012 Feb;4(1):22-8. doi: 10.1093/jmcb/mjr039. Epub 2011 Nov 22.
4
All-trans retinoic acid promotes TGF-β-induced Tregs via histone modification but not DNA demethylation on Foxp3 gene locus.全反式维甲酸通过组蛋白修饰而非 Foxp3 基因座上的 DNA 去甲基化促进 TGF-β 诱导的 Tregs。
PLoS One. 2011;6(9):e24590. doi: 10.1371/journal.pone.0024590. Epub 2011 Sep 13.
5
Sustained suppression by Foxp3+ regulatory T cells is vital for infectious transplantation tolerance.Foxp3+ 调节性 T 细胞的持续抑制对传染性移植耐受至关重要。
J Exp Med. 2011 Sep 26;208(10):2043-53. doi: 10.1084/jem.20110767. Epub 2011 Aug 29.
6
Indoleamine 2,3-dioxygenase is a signaling protein in long-term tolerance by dendritic cells.吲哚胺 2,3-双加氧酶是树突状细胞长期耐受中的信号蛋白。
Nat Immunol. 2011 Jul 31;12(9):870-8. doi: 10.1038/ni.2077.
7
Cutting edge: Human regulatory T cells require IL-35 to mediate suppression and infectious tolerance.前沿：人类调节性 T 细胞需要 IL-35 来介导抑制和感染性耐受。
J Immunol. 2011 Jun 15;186(12):6661-6. doi: 10.4049/jimmunol.1100315. Epub 2011 May 16.
8
Characterization of protective human CD4CD25 FOXP3 regulatory T cells generated with IL-2, TGF-β and retinoic acid.用 IL-2、TGF-β 和维 A 酸诱导产生的保护性人 CD4CD25 FOXP3 调节性 T 细胞的鉴定。
PLoS One. 2010 Dec 17;5(12):e15150. doi: 10.1371/journal.pone.0015150.
9
Myelin-reactive, TGF-β-induced regulatory T cells can be programmed to develop Th1-like effector function but remain less proinflammatory than myelin-reactive Th1 effectors and can suppress pathogenic T cell clonal expansion in vivo.髓鞘反应性、TGF-β诱导的调节性 T 细胞可被编程发展为 Th1 样效应功能，但比髓鞘反应性 Th1 效应物的炎症反应性更低，并且可以在体内抑制致病性 T 细胞克隆扩增。
J Immunol. 2010 Dec 15;185(12):7235-43. doi: 10.4049/jimmunol.1001551. Epub 2010 Nov 17.
10
Cutting edge: all-trans retinoic acid sustains the stability and function of natural regulatory T cells in an inflammatory milieu.前沿：全反式视黄酸在炎症环境中维持天然调节性 T 细胞的稳定性和功能。
J Immunol. 2010 Sep 1;185(5):2675-9. doi: 10.4049/jimmunol.1000598. Epub 2010 Aug 2.
Zotero 插件