-
摘要: 间充质干细胞(MSC)是一类具有自我更新、增殖和多向分化潜能的干细胞。研究表明,MSC具有低免疫源性,并且可以通过与细胞间直接接触或分泌细胞因子等方式发挥免疫调节作用。当前,MSC在治疗免疫相关性疾病中的研究是一个热点。为了更好了解MSC免疫方面的特性,本文就MSC的生物学特性和免疫调节作用作一综述。
-
表 1 MSC分泌的可溶性免疫调节因子及其生物功能
Table 1. Soluble immunomodulatory factors and its biological functions secreted by MSC
免疫调节因子 生物功能(含体内或体外实验) IDO 抑制T细胞增殖(体外),促进单核细胞向M2型Mφ分化(体外)[5],降低NK细胞活性(体外)[6] NO 抑制T细胞增殖(体外) sHLA-G 抑制PBMC反应[8] IL-6 抑制T细胞增殖(体外)[8],抑制DC分化(体外)[8] TSG-6 调节Mφ(体内、体外)[11],抑制炎症反应(体内)[12],抑制DC的成熟和功能(体外)[13] IL-1RA 诱导Mφ向M2型Mφ分化,抑制CD4+T细胞,抑制B细胞分化(体外)[15] TGF-β 促进Treg的产生(体外、体内)[7],抑制T细胞的增殖(体外)[8],抑制NK细胞的活化和功能(体外)[9] HGF 抑制T细胞增殖(体外)[8] LIF 促进T细胞增殖(体外)[8] IL-10 抑制T细胞增殖(体外)[8],抑制Th17细胞分化(体外)[10] PGE2 抑制T细胞增殖(体外)[8],诱导Treg生成(体外)[14],抑制NK细胞功能(体外)[6],诱导Mφ向M2型Mφ分化(体内、体外)[8],抑制DC成熟及其功能(体外) HO-1 抑制T细胞增殖(体内、体外),诱导Treg生成(体外)[16] 注:Mφ为巨噬细胞;NK细胞为自然杀伤细胞;Treg为调节性T细胞;DC为树突状细胞;Th17细胞为辅助性T细胞17;IDO为吲哚胺2,3-双加氧酶;TGF-β为转化生长因子-β;NO为一氧化氮;HGF为肝细胞生长因子;sHLA-G为人可溶性白细胞抗原G;PBMC为外周血单个核细胞;LIF为白血病抑制因子;IL-6为白细胞介素-6;IL-10为白细胞介素-10;TSG-6为肿瘤坏死因子α刺激基因-6;PGE2为前列腺素E2;IL-1RA为白细胞介素1受体拮抗剂;HO-1为血红素加氧酶-1;体外指体外实验,体内指体内实验 -
[1] Augello A,Kurth TB,De Bari C.Mesenchymal stem cells: a perspective from in vitro cultures to in vivo migration and niches[J].Eur Cell Mater,2010,20:121-133. http://cn.bing.com/academic/profile?id=2107989515&encoded=0&v=paper_preview&mkt=zh-cn [2] Bassi EJ, Aita CA,Cmara NO. Immune regulatory properties of multipotent mesenchymal stromal cells: where do we stand?[J]. World J Stem Cells,2011,3(1):1-8. doi: 10.4252/wjsc.v3.i1.1 [3] Lv FJ,Tuan RS,Cheung KM, et al. Concise review: the surface markers and identity of human mesenchymal stem cells[J].Stem Cells,2014,32(6):1408-1419. doi: 10.1002/stem.1681 [4] DelaRosa O,Lombardo E. Modulation of adult mesenchymal stem cells activity by toll-like receptors: implications on therapeutic potential[J].Mediators Inflamm,2010:865601. http://cn.bing.com/academic/profile?id=2005349078&encoded=0&v=paper_preview&mkt=zh-cn [5] François M, Romieu-Mourez R, Li M, et al. Human MSC suppression correlates with cytokine induction of indoleamine 2,3-dioxygenase and bystander M2 macrophage differentiation[J]. Mol Ther,2012,20(1):187-195. doi: 10.1038/mt.2011.189 [6] Kariminekoo S, Movassaghpour A, Rahimzadeh A, et al. Implications of mesenchymal stem cells in regenerative medicine[J]. Artif Cells Nanomed Biotechnol,2016,44(3):749-757. doi: 10.3109/21691401.2015.1129620 [7] Tasso R, Ilengo C, Quarto R, et al. Mesenchymal stem cells induce functionally active T-regulatory lymphocytes in a paracrine fashion and ameliorate experimental autoimmune uveitis[J]. Invest Ophthalmol Vis Sci, 2012, 53(2):786-793. doi: 10.1167/iovs.11-8211 [8] Fontaine MJ, Shih H, Schfer R, et al. Unraveling the mesenchymal stromal cells' paracrine immunomodulatory effects[J]. Transfus Med Rev,2016,30(1):37-43. doi: 10.1016/j.tmrv.2015.11.004 [9] Chatterjee D, Marquardt N, Tufa DM, et al. Human umbilical cord-derived mesenchymal stem cells utilize activin-A to suppress interferon-γ production by natural killer cells[J]. Front Immunol, 2014, 5:662. http://cn.bing.com/academic/profile?id=2049111133&encoded=0&v=paper_preview&mkt=zh-cn [10] Qu X, Liu X, Cheng K, et al. Mesenchymal stem cells inhibit Th17 cell differentiation by IL-10 secretion[J].Exp Hematol,2012,40(9):761-770. doi: 10.1016/j.exphem.2012.05.006 [11] Choi H, Lee RH, Bazhanov N, et al. Anti-inflammatory protein TSG-6 secreted by activated MSCs attenuates zymosan- induced mouse peritonitis by decreasing TLR2/NF-κB signaling in resident macrophages[J].Blood,2011,118(2):330-338. doi: 10.1182/blood-2010-12-327353 [12] Wang N, Li Q, Zhang L, et al. Mesenchymal stem cells attenuate peritoneal injury through secretion of TSG-6[J]. PLoS One,2012,7(8):e43768. doi: 10.1371/journal.pone.0043768 [13] Liu Y, Yin Z, Zhang R, et al. MSCs inhibit bone marrow-derived DC maturation and function through the release of TSG-6[J]. Biochem Biophys Res Commun, 2014, 450(4):1409-1415. doi: 10.1016/j.bbrc.2014.07.001 [14] Wang D, Huang S, Yuan X, et al. The regulation of the Treg/Th17 balance by mesenchymal stem cells in human systemic lupus erythematosus[J]. Cell Mol Immunol, 2015,DOI: 10.1038/cmi.2015.89[Epub ahead of print]. [15] Luz-Crawford P, Djouad F, Toupet K, et al. Mesenchymal stem cell-derived interleukin 1 receptor antagonist promotes macrophage polarization and inhibits B cell differentiation[J]. Stem Cells,2016,34(2):483-492. doi: 10.1002/stem.2254 [16] Mougiakakos D, Jitschin R, Johansson CC, et al. The impact of inflammatory licensing on heme oxygenase-1-mediated induction of regulatory T cells by human mesenchymal stem cells[J].Blood,2011,117(18):4826-4835. doi: 10.1182/blood-2010-12-324038 [17] Le Blanc K, Mougiakakos D. Multipotent mesenchymal stromal cells and the innate immune system[J].Nat Rev Immunol, 2012,12(5):383-396. doi: 10.1038/nri3209 [18] Melief SM, Schrama E, Brugman MH, et al. Multipotent stromal cells induce human regulatory T cells through a novel pathway involving skewing of monocytes toward anti-inflammatory macrophages[J]. Stem Cells,2013,31(9):1980-1991. doi: 10.1002/stem.1432 [19] Geng Y, Zhang L, Fu B, et al. Mesenchymal stem cells ameliorate rhabdomyolysis-induced acute kidney injury via the activation of M2 macrophages[J].Stem Cell Res Ther,2014,5(3):80. doi: 10.1186/scrt469 [20] Brandau S, Jakob M, Hemeda H, et al. Tissue-resident mesenchymal stem cells attract peripheral blood neutrophils and enhance their inflammatory activity in response to microbial challenge[J]. J Leukoc Biol,2010,88(5):1005-1015. doi: 10.1189/jlb.0410207 [21] Hall SR, Tsoyi K, Ith B, et al. Mesenchymal stromal cells improve survival during sepsis in the absence of heme oxygenase-1: the importance of neutrophils[J]. Stem Cells, 2013, 31(2):397-407. doi: 10.1002/stem.v31.2 [22] Spaggiari GM, Moretta L. Cellular and molecular interactions of mesenchymal stem cells in innate immunity[J]. Immunol Cell Biol,2013, 91(1):27-31. doi: 10.1038/icb.2012.62 [23] Moll G, Jitschin R, von Bahr L, et al. Mesenchymal stromal cells engage complement and complement receptor bearing innate effector cells to modulate immune responses[J]. PLoS One,2011,6(7):e21703. doi: 10.1371/journal.pone.0021703 [24] Tu Z, Li Q, Bu H, et al. Mesenchymal stem cells inhibit complement activation by secreting factor H[J].Stem Cells Dev,2010, 19(11):1803-1809. doi: 10.1089/scd.2009.0418 [25] Li Y, Lin F. Mesenchymal stem cells are injured by complement after their contact with serum[J].Blood,2012, 120(17):3436-3443. doi: 10.1182/blood-2012-03-420612 [26] Najar M, Raicevic G, Fayyad-Kazan H, et al. Immune-related antigens, surface molecules and regulatory factors in human-derived mesenchymal stromal cells: the expression and impact of inflammatory priming[J].Stem Cell Rev,2012,8(4):1188-1198. doi: 10.1007/s12015-012-9408-1 [27] Briones J, Novelli S, Sierra J. T-cell costimulatory molecules in acute-graft-versus host disease: therapeutic implications[J].Bone Marrow Res,2011:976793. http://cn.bing.com/academic/profile?id=2065828375&encoded=0&v=paper_preview&mkt=zh-cn [28] Di Nicola M, Carlo-Stella C, Magni M, et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli[J]. Blood,2002,99(10):3838-3843. doi: 10.1182/blood.V99.10.3838 [29] Su J, Chen X, Huang Y, et al. Phylogenetic distinction of iNOS and IDO function in mesenchymal stem cell-mediated immunosuppression in mammalian species[J].Cell Death Differ,2014,21(3):388-396. doi: 10.1038/cdd.2013.149 [30] Saldanha-Araujo F, Ferreira FI, Palma PV, et al. Mesenchymal stromal cells up-regulate CD39 and increase adenosine production to suppress activated T-lymphocytes[J]. Stem Cell Res,2011,7(1):66-74. doi: 10.1016/j.scr.2011.04.001 [31] Majumdar MK, Keane-Moore M, Buyaner D, et al. Characterization and functionality of cell surface molecules on human mesenchymal stem cells[J].J Biomed Sci,2003,10(2):228-241. doi: 10.1007/BF02256058 [32] Ren G, Zhao X, Zhang L, et al. Inflammatory cytokine-induced intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in mesenchymal stem cells are critical for immunosuppression[J].J Immunol,2010,184(5):2321-2328. doi: 10.4049/jimmunol.0902023 [33] de Mare-Bredemeijer EL, Mancham S, Verstegen MM, et al. Human graft-derived mesenchymal stromal cells potently suppress alloreactive T-cell responses[J]. Stem Cells Dev,2015,24(12):1436-1447. doi: 10.1089/scd.2014.0485 [34] Najar M, Raicevic G, Boufker HI, et al. Adipose-tissue-derived and Wharton's jelly-derived mesenchymal stromal cells suppress lymphocyte responses by secreting leukemia inhibitory factor[J]. Tissue Eng Part A,2010,16(11):3537-3546. doi: 10.1089/ten.tea.2010.0159 [35] Del Papa B, Sportoletti P, Cecchini D, et al. Notch1 modulates mesenchymal stem cells mediated regulatory T-cell induction[J]. Eur J Immunol,2013,43(1):182-187. doi: 10.1002/eji.201242643 [36] Li J, Zhuan-sun YX, Wen B,et al. Human mesenchymal stem cells elevate CD4+CD25+CD127low/- regulatory T cells of asthmatic patients via heme oxygenase-1[J]. Iran J Allergy Asthma Immunol,2013,12(3):228-235. http://cn.bing.com/academic/profile?id=2118259656&encoded=0&v=paper_preview&mkt=zh-cn [37] Yan Z, Zhuansun Y, Chen R, et al. Immunomodulation of mesenchymal stromal cells on regulatory T cells and its possible mechanism[J].Exp Cell Res,2014,324(1):65-74. doi: 10.1016/j.yexcr.2014.03.013 [38] Rosado MM, Bernardo ME, Scarsella M, et al. Inhibition of B-cell proliferation and antibody production by mesenchymal stromal cells is mediated by T cells[J].Stem Cells Dev,2015, 24(1):93-103. doi: 10.1089/scd.2014.0155
点击查看大图
表(1)
计量
- 文章访问数: 401
- HTML全文浏览量: 57
- PDF下载量: 25
- 被引次数: 0