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髓源性抑制细胞与移植免疫耐受研究进展

袁顺 王志维

袁顺, 王志维. 髓源性抑制细胞与移植免疫耐受研究进展[J]. 器官移植, 2020, 11(4): 435-442. doi: 10.3969/j.issn.1674-7445.2020.04.002
引用本文: 袁顺, 王志维. 髓源性抑制细胞与移植免疫耐受研究进展[J]. 器官移植, 2020, 11(4): 435-442. doi: 10.3969/j.issn.1674-7445.2020.04.002
Yuan Shun, Wang Zhiwei. Research progress on myeloid-derived suppressor cell and transplantation immune tolerance[J]. ORGAN TRANSPLANTATION, 2020, 11(4): 435-442. doi: 10.3969/j.issn.1674-7445.2020.04.002
Citation: Yuan Shun, Wang Zhiwei. Research progress on myeloid-derived suppressor cell and transplantation immune tolerance[J]. ORGAN TRANSPLANTATION, 2020, 11(4): 435-442. doi: 10.3969/j.issn.1674-7445.2020.04.002

髓源性抑制细胞与移植免疫耐受研究进展

doi: 10.3969/j.issn.1674-7445.2020.04.002
基金项目: 

国家自然科学基金 81570428

详细信息
    作者简介:

    袁顺,男,1992年生,硕士,研究方向为心脏移植,Email:2358643163@qq.com

    通讯作者:

    王志维,男,1962年生,博士,主任医师,博士研究生导师,研究方向为心脏移植、主动脉夹层发生机制及外科治疗,Email:wangzhiwei@whu.edu.cn

  • 中图分类号: R617, R329.4

Research progress on myeloid-derived suppressor cell and transplantation immune tolerance

More Information
  • 摘要: 髓源性抑制细胞(MDSC)是骨髓来源的一类异质性细胞群,最早在肿瘤中被发现,能够抑制T细胞的功能,具有免疫抑制作用。近年来越来越多的研究表明,在器官移植领域,MDSC对宿主的免疫功能也具有调节作用,能够诱导特异性免疫耐受,对移植器官发挥保护作用,有望成为临床上治疗移植排斥反应的新靶点。本文就MDSC的生物学特性和MDSC诱导免疫耐受的机制进行综述。

     

  • 图  1  MDSC的诱导分化过程

    Figure  1.  The induction and differentiation process of MDSC

    图  2  MDSC诱导移植免疫耐受的机制

    Figure  2.  Mechanism of transplantation immune tolerance induced by MDSC

    表  1  MDSC在器官移植免疫耐受中的作用的相关文献

    Table  1.   The relative literatures about the role of MDSC in immune tolerance of organ transplantation

    作者 年份 种属 器官 小分子物质 干预措施 结论
    Dugast, et al[17] 2008 大鼠 肾脏 iNOS 抗CD28抗体 抗CD28抗原诱导iNOS-MDSC分化,诱导移植免疫耐受
    Zhang, et al[18] 2008 小鼠 皮肤 精氨酸酶 ILT2抑制性受体 注射MDSC可延长移植皮肤存活时间
    Garcia, et al[19] 2010 小鼠 心脏 iNOS、精氨酸酶 抗CD40抗体 MDSC在移植物内聚集,诱导Treg分化
    Turnquist, et al[20] 2011 小鼠 心脏 iNOS、精氨酸酶 IL-33 IL-33诱导MDSC分化,但其不能延长移植物存活时间
    Adeegbe, et al[21] 2011 小鼠 皮肤 G-CSF、IL-2 MDSC和Treg协同作用,同种异体T细胞反应活性降低
    Chen, et al [22] 2012 小鼠 心脏 IDO ECDI-SP ECDI-SP对移植物的保护依赖于MDSC
    Arakawa, et al [23] 2014 小鼠 胰岛 iNOS GM-CSF、IL-4、肝星状细胞 体外诱导分化MDSC,具有保护同种异体胰岛作用
    Liao, et al[24] 2014 小鼠 皮肤 iNOS 地塞米松 糖皮质激素-糖皮质激素受体级联是地塞米松介导免疫抑制的关键
    Nakamura, et al[25] 2015 小鼠 心脏 iNOS 西罗莫司 mTOR、Raf/MEK/ERK信号通路在MDSC扩增中发挥重要作用
    Gajardo, et al[26] 2015 小鼠 皮肤 iNOS和精氨酸酶 IL-33 IL-33诱导MDSC分化,减轻排斥反应
    Nakamura, et al[27] 2016 小鼠 心脏 iNOS 西罗莫司 MDSC诱导移植物内Treg分化
    Zhao, et al[28] 2018 小鼠 心脏 iNOS 地塞米松 地塞米松能够诱导MDSC在移植物内聚集
    Nakao, et al[29] 2018 小鼠 心脏 iNOS 地塞米松 MDSC诱导Treg分化
    注:①ILT2为免疫球蛋白样转录物2。
    ②—为未提及。
    ③IDO为吲哚胺2,3-双加氧酶。
    ④ECDI-SP为碳二亚胺偶联脾淋巴细胞。
    ⑤mTOR为哺乳动物雷帕霉素靶蛋白。
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  • [1] FLEMING V, HU X, WEBER R, et al. Targeting myeloid-derived suppressor cells to bypass tumor-induced immunosuppression[J]. Front Immunol, 2018, 9: 398. DOI: 10.3389/fimmu.2018.00398.
    [2] ZHANG W, LI J, QI G, et al. Myeloid-derived suppressor cells in transplantation: the dawn of cell therapy[J]. J Transl Med, 2018, 16(1): 19. DOI: 10.1186/s12967-018-1395-9.
    [3] GARCIA AJ, RUSCETTI M, ARENZANA TL, et al. Pten null prostate epithelium promotes localized myeloid-derived suppressor cell expansion and immune suppression during tumor initiation and progression[J]. Mol Cell Biol, 2014, 34(11): 2017-2028. DOI: 10.1128/MCB.00090-14.
    [4] FUJⅡ W, ASHIHARA E, HIRAI H, et al. Myeloid-derived suppressor cells play crucial roles in the regulation of mouse collagen-induced arthritis[J]. J Immunol, 2013, 191(3): 1073-1081. DOI: 10.4049/jimmunol.1203535.
    [5] AARTS CEM, KUIJPERS TW. Neutrophils as myeloid-derived suppressor cells[J]. Eur J Clin Invest, 2018, 48 (Suppl 2): e12989. DOI: 10.1111/eci.12989.
    [6] HAILE LA, GAMREKELASHVILI J, MANNS MP, et al. CD49d is a new marker for distinct myeloid-derived suppressor cell subpopulations in mice[J]. J Immunol, 2010, 185(1): 203-210. DOI: 10.4049/jimmunol.0903573.
    [7] JITSCHIN R, BRAUN M, BÜTTNER M, et al. CLL-cells induce IDOhi CD14+HLADRlo myeloid-derived suppressor cells that inhibit T-cell responses and promote Tregs[J]. Blood, 2014, 124(5): 750-760. DOI: 10.1182/blood-2013-12-546416.
    [8] VASQUEZ-DUNDDEL D, PAN F, ZENG Q, et al. STAT3 regulates arginase-I in myeloid-derived suppressor cells from cancer patients[J]. J Clin Invest, 2013, 123(4): 1580-1589. doi: 10.1172/JCI60083
    [9] GABRILOVICH DI, NAGARAJ S. Myeloid-derived suppressor cells as regulators of the immune system[J]. Nat Rev Immunol, 2009, 9(3): 162-174. DOI: 10.1038/nri2506.
    [10] LUAN Y, MOSHEIR E, MENON MC, et al. Monocytic myeloid-derived suppressor cells accumulate in renal transplant patients and mediate CD4(+) Foxp3(+) Treg expansion[J]. Am J Transplant, 2013, 13(12): 3123-3131. DOI: 10.1111/ajt.12461.
    [11] BRONTE V, BRANDAU S, CHEN SH, et al. Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards[J]. Nat Commun, 2016, 7: 12150. DOI: 10.1038/ncomms12150.
    [12] CONDAMINE T, MASTIO J, GABRILOVICH DI. Transcriptional regulation of myeloid-derived suppressor cells[J]. J Leukoc Biol, 2015, 98(6): 913-922. DOI: 10.1189/jlb.4RI0515-204R.
    [13] MARIGO I, BOSIO E, SOLITO S, et al. Tumor-induced tolerance and immune suppression depend on the C/EBPbeta transcription factor[J]. Immunity, 2010, 32(6): 790-802. DOI: 10.1016/j.immuni.2010.05.010.
    [14] HIGHFILL SL, RODRIGUEZ PC, ZHOU Q, et al. Bone marrow myeloid-derived suppressor cells (MDSCs) inhibit graft-versus-host disease (GVHD) via an arginase-1-dependent mechanism that is up-regulated by interleukin-13[J]. Blood, 2010, 116(25): 5738-5747. DOI: 10.1182/blood-2010-06-287839.
    [15] LECHNER MG, LIEBERTZ DJ, EPSTEIN AL. Characterization of cytokine-induced myeloid-derived suppressor cells from normal human peripheral blood mononuclear cells[J]. J Immunol, 2010, 185(4): 2273-2284. DOI: 10.4049/jimmunol.1000901.
    [16] OBERMAJER N, KALINSKI P. Generation of myeloid-derived suppressor cells using prostaglandin E2[J]. Transplant Res, 2012, 1(1): 15. DOI: 10.1186/2047-1440-1-15.
    [17] DUGAST AS, HAUDEBOURG T, COULON F, et al. Myeloid-derived suppressor cells accumulate in kidney allograft tolerance and specifically suppress effector T cell expansion[J]. J Immunol, 2008, 180(12): 7898-7906. doi: 10.4049/jimmunol.180.12.7898
    [18] ZHANG W, LIANG S, WU J, et al. Human inhibitory receptor immunoglobulin-like transcript 2 amplifies CD11b+Gr1+ myeloid-derived suppressor cells that promote long-term survival of allografts[J]. Transplantation, 2008, 86(8): 1125-1134. DOI: 10.1097/TP.0b013e318186fccd.
    [19] GARCIA MR, LEDGERWOOD L, YANG Y, et al. Monocytic suppressive cells mediate cardiovascular transplantation tolerance in mice[J]. J Clin Invest, 2010, 120(7): 2486-2496. DOI: 10.1172/JCI41628.
    [20] TURNQUIST HR, ZHAO Z, ROSBOROUGH BR, et al. IL-33 expands suppressive CD11b+ Gr-1int and regulatory T cells, including ST2L+ Foxp3+ cells, and mediates regulatory T cell-dependent promotion of cardiac allograft survival[J]. J Immunol, 2011, 187(9): 4598-4610. DOI: 10.4049/jimmunol.1100519.
    [21] ADEEGBE D, SERAFINI P, BRONTE V, et al. In vivo induction of myeloid suppressor cells and CD4+Foxp3+ T regulatory cells prolongs skin allograft survival in mice[J]. Cell Transplant, 2011, 20(6): 941-954. DOI: 10.3727/096368910X540621.
    [22] CHEN G, KHERADMAND T, BRYANT J, et al. Intragraft CD11b+ IDO+ cells mediate cardiac allograft tolerance by ECDI-fixed donor splenocyte infusions[J]. Am J Transplant, 2012, 12(11): 2920-2929. DOI: 10.1111/j.1600-6143.2012.04203.x.
    [23] ARAKAWA Y, QIN J, CHOU HS, et al. Cotransplantation with myeloid-derived suppressor cells protects cell transplants: a crucial role of inducible nitric oxide synthase[J]. Transplantation, 2014, 97(7): 740-747. DOI: 10.1097/01.TP.0000442504.23885.f7.
    [24] LIAO J, WANG X, BI Y, et al. Dexamethasone potentiates myeloid-derived suppressor cell function in prolonging allograft survival through nitric oxide[J]. J Leukoc Biol, 2014, 96(5): 675-684. DOI: 10.1189/jlb.2HI1113-611RR.
    [25] NAKAMURA T, NAKAO T, YOSHIMURA N, et al. Rapamycin prolongs cardiac allograft survival in a mouse model by inducing myeloid-derived suppressor cells[J]. Am J Transplant, 2015, 15(9): 2364-2377. DOI: 10.1111/ajt.13276.
    [26] GAJARDO T, MORALES RA, CAMPOS-MORA M, et al. Exogenous interleukin-33 targets myeloid-derived suppressor cells and generates periphery-induced Foxp3+ regulatory T cells in skin-transplanted mice[J]. Immunology, 2015, 146(1): 81-88. DOI: 10.1111/imm.12483.
    [27] NAKAMURA T, NAKAO T, ASHIHARA E, et al. Myeloid-derived suppressor cells recruit CD4+/Foxp3+ regulatory T cells in a murine cardiac allograft[J]. Transplant Proc, 2016, 48(4): 1275-1278. DOI: 10.1016/j.transproceed.2015.10.060.
    [28] ZHAO Y, SHEN XF, CAO K, et al. Dexamethasone-induced myeloid-derived suppressor cells prolong allo cardiac graft survival through iNOS- and glucocorticoid receptor-dependent mechanism[J]. Front Immunol, 2018, 9: 282. DOI: 10.3389/fimmu.2018.00282.
    [29] NAKAO T, NAKAMURA T, MASUDA K, et al. Dexamethasone prolongs cardiac allograft survival in a murine model through myeloid-derived suppressor cells[J]. Transplant Proc, 2018, 50(1): 299-304. DOI: 10.1016/j.transproceed.2017.11.014.
    [30] SAVAGE TM, SHONTS BA, OBRADOVIC A, et al. Early expansion of donor-specific Tregs in tolerant kidney transplant recipients[J]. JCI Insight, 2018, 3(22):124086. DOI: 10.1172/jci.insight.124086.
    [31] HUANG B, PAN PY, LI Q, et al. Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host[J]. Cancer Res, 2006, 66(2): 1123-1131. doi: 10.1158-0008-5472.CAN-05-1299/
    [32] KANG X, ZHANG X, LIU Z, et al. Granulocytic myeloid-derived suppressor cells maintain feto-maternal tolerance by inducing Foxp3 expression in CD4+CD25T cells by activation of the TGF-β/β-catenin pathway[J]. Mol Hum Reprod, 2016, 22(7): 499-511. DOI: 10.1093/molehr/gaw026.
    [33] PARK MJ, LEE SH, KIM EK, et al. Interleukin-10 produced by myeloid-derived suppressor cells is critical for the induction of Tregs and attenuation of rheumatoid inflammation in mice[J]. Sci Rep, 2018, 8(1): 3753. DOI: 10.1038/s41598-018-21856-2.
    [34] LEE CR, KWAK Y, YANG T, et al. Myeloid-derived suppressor cells are controlled by regulatory T cells via TGF-beta during murine colitis[J]. Cell Rep, 2016, 17(12): 3219-3232. DOI: 10.1016/j.celrep.2016.11.062.
    [35] OKANO S, ABU-ELMAGD K, KISH DD, et al. Myeloid-derived suppressor cells increase and inhibit donor-reactive T cell responses to graft intestinal epithelium in intestinal transplant patients[J]. Am J Transplant, 2018, 18(10): 2544-2558. DOI: 10.1111/ajt.14718.
    [36] KIM JI, LEE MK 4TH, MOORE DJ, et al. Regulatory T-cell counter-regulation by innate immunity is a barrier to transplantation tolerance[J]. Am J Transplant, 2009, 9(12): 2736-2744. DOI: 10.1111/j.1600-6143.2009.02847.x.
    [37] QIAN C, CAO X. Dendritic cells in the regulation of immunity and inflammation[J]. Semin Immunol, 2018, 35: 3-11. DOI: 10.1016/j.smim.2017.12.002.
    [38] MANNON RB. Macrophages: contributors to allograft dysfunction, repair, or innocent bystanders?[J]. Curr Opin Organ Transplant, 2012, 17(1): 20-25. DOI: 10.1097/MOT.0b013e32834ee5b6.
    [39] PANG XL, WANG ZG, LIU L, et al. Immature dendritic cells derived exosomes promotes immune tolerance by regulating T cell differentiation in renal transplantation[J]. Aging (Albany NY), 2019, 11(20): 8911-8924. DOI: 10.18632/aging.102346.
    [40] TSE GH, HUGHES J. Macrophages and transplant rejection: a novel future target?[J]. Transplantation, 2013, 96(11): 946-948. DOI: 10.1097/TP.0b013e3182a4bf20.
    [41] ZAHORCHAK AF, MACEDO C, HAMM DE, et al. High PD-L1/CD86 MFI ratio and IL-10 secretion characterize human regulatory dendritic cells generated for clinical testing in organ transplantation[J]. Cell Immunol, 2018, 323: 9-18. DOI: 10.1016/j.cellimm.2017.08.008.
    [42] RIQUELME P, HAARER J, KAMMLER A, et al. TIGIT+ iTregs elicited by human regulatory macrophages control T cell immunity[J]. Nat Commun, 2018, 9(1): 2858. DOI: 10.1038/s41467-018-05167-8.
    [43] EVERLY MJ, EVERLY JJ, AREND LJ, et al. Reducing de novo donor-specific antibody levels during acute rejection diminishes renal allograft loss[J]. Am J Transplant, 2009, 9(5): 1063-1071. DOI: 10.1111/j.1600-6143.2009.02577.x.
    [44] GOODE I, XU H, ILDSTAD ST. Regulatory B cells: the new "it" cell[J]. Transplant Proc, 2014, 46(1): 3-8. DOI: 10.1016/j.transproceed.2013.08.075.
    [45] ÖZKAN B, LIM H, PARK SG. Immunomodulatory function of myeloid-derived suppressor cells during B cell-mediated immune responses[J]. Int J Mol Sci, 2018, 19(5):E1468. DOI: 10.3390/ijms19051468.
    [46] PARK MJ, LEE SH, KIM EK, et al. Myeloid-derived suppressor cells induce the expansion of regulatory B cells and ameliorate autoimmunity in the sanroque mouse model of systemic lupus erythematosus[J]. Arthritis Rheumatol, 2016, 68(11): 2717-2727. DOI: 10.1002/art.39767.
    [47] SHEN M, WANG J, YU W, et al. A novel MDSC-induced PD-1-PD-L1+ B-cell subset in breast tumor microenvironment possesses immuno-suppressive properties[J]. Oncoimmunology, 2018, 7(4):e1413520. DOI: 10.1080/2162402X.2017.1413520.
    [48] GAZDIC M, SIMOVIC MARKOVIC B, VUCICEVIC L, et al. Mesenchymal stem cells protect from acute liver injury by attenuating hepatotoxicity of liver natural killer T cells in an inducible nitric oxide synthase- and indoleamine 2, 3-dioxygenase-dependent manner[J]. J Tissue Eng Regen Med, 2018, 12(2): e1173-e1185. DOI: 10.1002/term.2452.
    [49] XUE Q, YAN Y, ZHANG R, et al. Regulation of iNOS on immune cells and its role in diseases[J]. Int J Mol Sci, 2018, 19(12):E3805. DOI: 10.3390/ijms19123805.
    [50] CZYSTOWSKA-KUZMICZ M, SOSNOWSKA A, NOWIS D, et al. Small extracellular vesicles containing arginase-1 suppress T-cell responses and promote tumor growth in ovarian carcinoma[J]. Nat Commun, 2019, 10(1): 3000. DOI: 10.1038/s41467-019-10979-3.
    [51] NELP MT, KATES PA, HUNT JT, et al. Immune-modulating enzyme indoleamine 2, 3-dioxygenase is effectively inhibited by targeting its apo-form[J]. Proc Natl Acad Sci U S A, 2018, 115(13): 3249-3254. DOI: 10.1073/pnas.1719190115.
    [52] MOUGIAKAKOS D, JITSCHIN R, VON BAHR L, et al. Immunosuppressive CD14+HLADRlow/neg IDO+ myeloid cells in patients following allogeneic hematopoietic stem cell transplantation[J]. Leukemia, 2013, 27(2): 377-388. DOI: 10.1038/leu.2012.215.
    [53] MAEDA A, EGUCHI H, NAKAHATA K, et al. Monocytic MDSCs regulate macrophage-mediated xenogenic cytotoxicity[J]. Transpl Immunol, 2015, 33(2): 140-145. DOI: 10.1016/j.trim.2015.07.002.
    [54] WANG X, BI Y, XUE L, et al. The calcineurin-NFAT axis controls allograft immunity in myeloid-derived suppressor cells through reprogramming T cell differentiation[J]. Mol Cell Biol, 2015, 35(3): 598-609. DOI: 10.1128/MCB.01251-14.z
    [55] HOLMGAARD RB, ZAMARIN D, LI Y, et al. Tumor-expressed IDO recruits and activates MDSCs in a Treg-dependent manner[J]. Cell Rep, 2015, 13(2): 412-424. DOI: 10.1016/j.celrep.2015.08.077.
    [56] SUN C, MEZZADRA R, SCHUMACHER TN. Regulation and function of the PD-L1 checkpoint[J]. Immunity, 2018, 48(3): 434-452. DOI: 10.1016/j.immuni.2018.03.014.
    [57] DENG L, LIANG H, BURNETTE B, et al. Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice[J]. J Clin Invest, 2014, 124(2): 687-695. DOI: 10.1172/JCI67313.
    [58] GAO W, DEMIRCI G, STROM TB, et al. Stimulating PD-1-negative signals concurrent with blocking CD154 co-stimulation induces long-term islet allograft survival[J]. Transplantation, 2003, 76(6): 994-999. doi: 10.1097/01.TP.0000085010.39567.FB
    [59] LIGOCKI AJ, NIEDERKORN JY. Advances on non-CD4+ Foxp3+ T regulatory cells: CD8+, type 1, and double negative T regulatory cells in organ transplantation[J]. Transplantation, 2015, 99(8): 1553-1559.DOI: 10.1097/TP.0000000000000813.
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  • 收稿日期:  2020-04-02
  • 网络出版日期:  2021-01-19
  • 刊出日期:  2020-07-15

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