综述

FOXP3+调节性T细胞与免疫细胞治疗

  • 刘鑫男 ,
  • 赵彬彬 ,
  • 成浩 ,
  • 李斌
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  • 1. 上海交通大学医学院, 上海市免疫学研究所, 上海 200025;
    2. 中国科学院上海巴斯德研究所, 上海 200025
刘鑫男,博士研究生,研究方向为分子免疫学,电子信箱:liu_xjll@163.com

收稿日期: 2018-03-11

  修回日期: 2018-10-08

  网络出版日期: 2019-04-01

基金资助

国家自然科学基金杰出青年基金项目(31525008)

FOXP3+ Treg cells and immune cell therapy

  • LIU Xinnan ,
  • ZHAO Binbin ,
  • CHENG Hao ,
  • LI Bin
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  • 1. Medicine Shanghai Institute of Immunology, Shanghai Jiao Tong University School, Shanghai 200025, China;
    2. Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200025, China

Received date: 2018-03-11

  Revised date: 2018-10-08

  Online published: 2019-04-01

摘要

CD4+CD25+FOXP3+调节性T细胞(Treg)负责维持机体免疫稳态、调节免疫耐受。Treg细胞通过调控机体对外来或自身抗原的免疫应答水平,在抗自身免疫及抗肿瘤免疫中均发挥重要作用。深入分析了Treg细胞功能的分子机理,通过FOXP3+Treg细胞体外扩增或对其进行修饰改造,可以使其在不同组织及炎症微环境下特异性促进对机体的有益作用,减少副作用,这一现象会为免疫细胞治疗提供新思路与新策略。

本文引用格式

刘鑫男 , 赵彬彬 , 成浩 , 李斌 . FOXP3+调节性T细胞与免疫细胞治疗[J]. 科技导报, 2019 , 37(5) : 72 -80 . DOI: 10.3981/j.issn.1000-7857.2019.05.010

Abstract

Regulatory T(Treg) cells play a key role in the maintenance of immune homeostasis and immune tolerance. Treg cells can suppress the immune response to neoantigen and autologous antigen to control anti-tumor immunity and autoimmunity. In vitro proliferated natural or modified Treg cells can be adoptively transferred into host to promote beneficial effect or reduce side effect in different inflammatory tissue microenvironments, which may provide new approach and strategy for treating inflammatory diseases.

参考文献

[1] Li Z, Li D, Tsun A, et al. FOXP3+ regulatory T cells and their functional regulation[J]. Cellular & Molecular Immunology, 2015, 12(5):558-565.
[2] Sakaguchi S, Vignali D A, Rudensky A Y, et al. The plasticity and stability of regulatory T cells[J]. Nature Reviews Immunology, 2013, 13(6):461-467.
[3] Avci C B, Dodurga Y, Gundogdu G, et al. Regulation of URG4/URGCP and PPARalpha gene expressions after retinoic acid treatment in neuroblastoma cells[J]. Tumour Biology, 2013, 34(6):3853-3857.
[4] O'rourke D M, Nasrallah M P, Desai A, et al. A single dose of peripherally infused EGFRvⅢ-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma[J]. Science Translational Medicine, 2017, 9(399):eaaa0984.
[5] Abramson J S, Mcgree B, Noyes S, et al. Anti-CD19 CAR T cells in CNS diffuse large-B-Cell lymphoma[J]. New England Journal of Medicine, 2017, 377(8):783-784.
[6] Zhen A, Peterson C W, Carrillo M A, et al. Long-term persistence and function of hematopoietic stem cell-derived chimeric antigen receptor T cells in a nonhuman primate model of HIV/AIDS[J]. PLoS Pathogens, 2017, 13(12):e1006753.
[7] Zhou Z C, Wang J, Cai Z H, et al. Association between vitamin D receptor gene Cdx2 polymorphism and breast cancer susceptibility[J]. Tumour Biology, 2013, 34(6):3437-3441.
[8] Geiger T L, Tauro S. Nature and nurture in Foxp3(+) regulatory T cell development, stability, and function[J]. Human Immunology, 2012, 73(3):232-239.
[9] Shevach E M, Thornton A M. tTregs, pTregs, and iTregs:similarities and differences[J]. Immunological Reviews, 2014, 259(1):88-102.
[10] Vieira P L, Christensen J R, Minaee S, Et Al. IL-10-secreting regulatory T cells do not express Foxp3 but have comparable regulatory function to naturally occurring CD4+CD25+ regulatory T cells[J]. Journal of Immunology, 2004, 172(10):5986-5993.
[11] Weiner H L. Induction and mechanism of action of transforming growth factor-beta-secreting Th3 regulatory cells[J]. Immunological Reviews, 2001, 182(207-214.
[12] Hori S, Sakaguchi S. Foxp3:A critical regulator of the development and function of regulatory T cells[J]. Microbes and Infection, 2004, 6(8):745-751.
[13] Tang Q, Bluestone J A. The Foxp3+ regulatory T cell:A jack of all trades, master of regulation[J]. Nature Immunology, 2008, 9(3):239-244.
[14] Ostmann A, Paust H J, Panzer U, et al. Regulatory T cell-derived IL-10 ameliorates crescentic GN[J]. Journal of the American Society of Nephrology, 2013, 24(6):930-942.
[15] Frimpong-Boateng K, Van Rooijen N, Geiben-Lynn R. Regulatory T cells suppress natural killer cells during plasmid DNA vaccination in mice, blunting the CD8+ T cell immune response by the cytokine TGFbeta[J]. PloS One, 2010, 5(8):e12281.
[16] Collison L W, Workman C J, Kuo T T, Et Al. The inhibitory cytokine IL-35 contributes to regulatory T-cell function[J]. Nature, 2007, 450(7169):566-569.
[17] Read S, Malmstrom V, Powrie F. Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation[J]. Journal of Experimental Medicine, 2000, 192(2):295-302.
[18] Oderup C, Cederbom L, Makowska A, et al. Cytotoxic T lymphocyte antigen-4-dependent down-modulation of costimulatory molecules on dendritic cells in CD4+ CD25+ regulatory Tcell-mediated suppression[J]. Immunology, 2006, 118(2):240-249.
[19] Mellor A L, Munn D H. IDO expression by dendritic cells:tolerance and tryptophan catabolism[J]. Nature Reviews:Immunology, 2004, 4(10):762-774.
[20] Huang C T, Workman C J, Flies D, et al. Role of LAG-3 in regulatory T cells[J]. Immunity, 2004, 21(4):503-513.
[21] Liang B, Workman C, Lee J, et al. Regulatory T cells inhibit dendritic cells by lymphocyte activation gene-3 engagement of MHC class Ⅱ[J]. Journal of Immunology, 2008, 180(9):5916-5926.
[22] Zhao D M, Thornton A M, Dipaolo R J, et al. Activated CD4+ CD25+ T cells selectively kill B lymphocytes[J]. Blood, 2006, 107(10):3925-3932.
[23] Ren X, Ye F, Jiang Z, et al. Involvement of cellular death in TRAIL/DR5-dependent suppression induced by CD4(+)CD25(+) regulatory T cells[J]. Cell Death and Differentiation, 2007, 14(12):2076-2084.
[24] Oberle N, Eberhardt N, Falk C S, et al. Rapid suppression of cytokine transcription in human CD4+CD25 T cells by CD4+ Foxp3+ regulatory T cells:independence of IL-2 consumption, TGF-beta, and various inhibitors of TCR signaling[J]. Journal of Immunology, 2007, 179(6):3578-3587.
[25] Deaglio S, Dwyer K M, Gao W, et al. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression[J]. Journal of Experimental Medicine, 2007, 204(6):1257-1265.
[26] Zarek P E, Huang C T, Lutz E R, et al. A2A receptor signaling promotes peripheral tolerance by inducing T-cell anergy and the generation of adaptive regulatory T cells[J]. Blood, 2008, 111(1):251-259.
[27] Bopp T, Becker C, Klein M, et al. Cyclic adenosine monophosphate is a key component of regulatory T cell-mediated suppression[J]. Journal of Experimental Medicine, 2007, 204(6):1303-1310.
[28] Tai X, Cowan M, Feigenbaum L, et al. CD28 costimulation of developing thymocytes induces Foxp3 expression and regulatory T cell differentiation independently of interleukin 2[J]. Nature Immunology, 2005, 6(2):152-162.
[29] Long M, Park S G, Strickland I, Et Al. Nuclear factor-kappaB modulates regulatory T cell development by directly regulating expression of Foxp3 transcription factor[J]. Immunity, 2009, 31(6):921-931.
[30] Mantel P Y, Ouaked N, Ruckert B, et al. Molecular mechanisms underlying FOXP3 induction in human T cells[J]. Journal of Immunology, 2006, 176(6):3593-3602.
[31] Yao Z, Kanno Y, Kerenyi M, Et Al. Nonredundant roles for Stat5a/b in directly regulating Foxp3[J]. Blood, 2007, 109(10):4368-4375.
[32] Burchill M A, Yang J, Vogtenhuber C, et al. IL-2 receptor beta-dependent STAT5 activation is required for the development of Foxp3+ regulatory T cells[J]. Journal of Immunology, 2007, 178(1):280-290.
[33] Zheng Y, Josefowicz S, Chaudhry A, et al. Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory Tcell fate[J]. Nature, 2010, 463(7282):808-812.
[34] Laurence A, Tato C M, Davidson T S, et al. Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation[J]. Immunity, 2007, 26(3):371-381.
[35] Liu Y, Wang L, Predina J, et al. Inhibition of p300 impairs Foxp3(+) T regulatory cell function and promotes antitumor immunity[J]. Nature Medicine, 2013, 19(9):1173-1177.
[36] Van Loosdregt J, Brunen D, Fleskens V, et al. Rapid temporal control of Foxp3 protein degradation by sirtuin-1[J]. PloS One, 2011, 6(4):e19047.
[37] Nie H, Zheng Y, Li R, Et Al. Phosphorylation of FOXP3 controls regulatory T cell function and is inhibited by TNF-alpha in rheumatoid arthritis[J]. Nature Medicine, 2013, 19(3):322-328.
[38] Chunder N, Wang L, Chen C, et al. Cyclin-dependent kinase 2 controls peripheral immune tolerance[J]. Journal of Immunology, 2012, 189(12):5659-5666.
[39] Bayer A L, Pugliese A, Malek T R. The IL-2/IL-2R system:from basic science to therapeutic applications to enhance immune regulation[J]. Immunologic Research, 2013, 57(1-3):197-209.
[40] Chen Z, Barbi J, Bu S, et al. The ubiquitin ligase Stub1 negatively modulates regulatory T cell suppressive activity by promoting degradation of the transcription factor Foxp3[J]. Immunity, 2013, 39(2):272-285.
[41] Van Loosdregt J, Fleskens V, Fu J, et al. Stabilization of the transcription factor Foxp3 by the deubiquitinase USP7 increases Treg-cell-suppressive capacity[J]. Immunity, 2013, 39(2):259-271.
[42] Luo X, Nie J, Wang S, Et Al. Poly(ADP-ribosyl)ation of FOXP3 protein mediated by PARP-1 regulates the function of regulatory T cells[J]. Journal of Biological Chemistry, 2016, 291(3):1201.
[43] Mays L E, Ammon-Treiber S, Mothes B, et al. Modified Foxp3 mRNA protects against asthma through an IL-10-dependent mechanism[J]. Journal of Clinical Investigation, 2013, 123(3):1216-1228.
[44] Mo J H, Chung Y J, Kim J H. T cell transcriptional factors in allergic rhinitis and its association with clinical features[J]. Asia Pacific Allergy, 2013, 3(3):186-193.
[45] Yin Y, Wu M, Nie G, et al. HtrA3 is negatively correlated with lymph node metastasis in invasive ductal breast cancer[J]. Tumour Biology, 2013, 34(6):3611-3617.
[46] Kabbage M, Trimeche M, Ben Nasr H, et al. Tropomyosin-4 correlates with higher SBR grades and tubular differentiation in infiltrating ductal breast carcinomas:an immunohistochemical and proteomics-based study[J]. Tumour Biology, 2013, 34(6):3593-3602.
[47] Zou W. Regulatory T cells, tumour immunity and immunotherapy[J]. Nature Reviews:Immunology, 2006, 6(4):295-307.
[48] Nishikawa H, Kato T, Tawara I, et al. Definition of target antigens for naturally occurring CD4(+) CD25(+) regulatory T cells[J]. Journal of Experimental Medicine, 2005, 201(5):681-686.
[49] CHAUDARY N, HILL R P. Hypoxia and metastasis[J]. Clinical Cancer Research, 2007, 13(7):1947-1949.
[50] Pan X D, Mao Y Q, Zhu L J, et al. Changes of regulatory T cells and FoxP3 gene expression in the aging process and its relationship with lung tumors in humans and mice[J]. Chinese Medical Journal (Engl.), 2012, 125(11):2004-2011.
[51] Ye L, Guan S, Zhang C, et al. Circulating autoantibody to FOXP3 may be a potential biomarker for esophageal squamous cell carcinoma[J]. Tumour Biology, 2013, 34(3):1873-1877.
[52] Mcinnes N, Sadlon T J, Brown C Y, et al. FOXP3 and FOXP3-regulated microRNAs suppress SATB1 in breast cancer cells[J]. Oncogene, 2012, 31(8):1045-1054.
[53] Trzonkowski P, Bieniaszewska M, Juscinska J, et al. First-inman clinical results of the treatment of patients with graft versus host disease with human ex vivo expanded CD4+ CD25+ CD127-T regulatory cells[J]. Clinical Immunology, 2009, 133(1):22-26.
[54] Di Ianni M, Falzetti F, Carotti A, et al. Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation[J]. Blood, 2011, 117(14):3921-3928.
[55] Brunstein C G, Blazar B R, Miller J S, et al. Adoptive transfer of umbilical cord blood-derived regulatory T cells and early viral reactivation[J]. Biology of Blood and Marrow Transplantation, 2013, 19(8):1271-1273.
[56] Marek-Trzonkowska N, Mysliwec M, Siebert J, et al. Clinical application of regulatory T cells in type 1 diabetes[J]. Pediatric Diabetes, 2013, 14(5):322-332.
[57] Ji W W, Li R P, Li M, et al. Antidepressant-like effect of essential oil of Perilla frutescens in a chronic, unpredictable, mild stress-induced depression model mice[J]. Chinese Journal of Natural Medicines, 2014, 12(10):753-759.
[58] Lin F, Luo X, Tsun A, et al. Kaempferol enhances the suppressive function of Treg cells by inhibiting FOXP3 phosphorylation[J]. International Immunopharmacology, 2015, 28(2):859-865.
[59] DENG G, NAGAI Y, XIAO Y, et al. Pim-2 Kinase Influences Regulatory T Cell Function and Stability by Mediating Foxp3 Protein N-terminal Phosphorylation[J]. Journal of Biological Chemistry, 2015, 290(33):20211-20220.
[60] Elinav E, Waks T, Eshhar Z. Redirection of regulatory T cells with predetermined specificity for the treatment of experimental colitis in mice[J]. Gastroenterology, 2008, 134(7):2014-2024.
[61] Hemmer B, Kerschensteiner M, Korn T. Role of the innate and adaptive immune responses in the course of multiple sclerosis[J]. The Lancet Neurology, 2015, 14(4):406-419.
[62] Liu Y, Yang N, Zuo P. cDNA microarray analysis of gene expression in the cerebral cortex and hippocampus of BALB/c mice subjected to chronic mild stress[J]. Cellular and Molecular Neurobiology, 2010, 30(7):1035-1047.
[63] Macdonald K G, Hoeppli R E, Huang Q, et al. Alloantigenspecific regulatory T cells generated with a chimeric antigen receptor[J]. Journal of Clinical Investigation, 2016, 126(4):1413-1424.
[64] Blat D, Zigmond E, Alteber Z, et al. Suppression of murine colitis and its associated cancer by carcinoembryonic antigenspecific regulatory T cells[J]. Molecular Theraphy, 2014, 22(5):1018-1028.
[65] Smith T T, Stephan S B, Moffett H F, et al. In situ programming of leukaemia-specific T cells using synthetic DNA nanocarriers[J]. Nat Nanotechnol, 2017, 12(8):813-820.
[66] Eyquem J, Mansilla-Soto J, Giavridis T, et al. Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection[J]. Nature, 2017, 543(7643):113-117.
[67] Pogulis R J, Pease L R. A retroviral vector that directs simultaneous expression of alpha and beta T cell receptor genes[J]. Human Gene Therapy, 1998, 9(15):2299-2304.
[68] Gulley J L, Arlen P M, Tsang K Y, et al. Pilot study of vaccination with recombinant CEA-MUC-1-TRICOM poxviralbased vaccines in patients with metastatic carcinoma[J]. Clinical Cancer Research, 2008, 14(10):3060-3069.
[69] Robbins P F, Morgan R A, Feldman S A, et al. Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1[J]. Journal of Clinical Oncology, 2011, 29(7):917-924.
[70] Bilusic M, Heery C R, Arlen P M, et al. Phase I trial of a recombinant yeast-CEA vaccine (GI-6207) in adults with metastatic CEA-expressing carcinoma[J]. Cancer Immunology, Immunotherapy, 2014, 63(3):225-234.
[71] Klebanoff C A, Rosenberg S A, Restifo N P. Prospects for gene-engineered T cell immunotherapy for solid cancers[J]. Nature Medicine, 2016, 22(1):26-36.
[72] Attridge K, Walker L S. Homeostasis and function of regulatory T cells (Tregs) in vivo:lessons from TCR-transgenic Tregs[J]. Immunological Reviews, 2014, 259(1):23-39.
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