144 2012 5 6 2 Chin J Transplant Electronic Edition May 2012Vol 6No. 2 吴婷婷 赵勇 MDSC T MDSC MDSC MDSC MDSC T T MDSC Regulation of myeloid derived suppressor cells and its role in transplantation WU Ting-ting ZHAO Yong. State Key Laboratory of Biomembrane and Membrane BiotechnologyInstitute of Zoology Chinese Academy of SciencesBeijing 100101China Corresponding authorzhao YongEmailzhaoy@ ioz. ac. cn Abstract Myeloid derived suppressor cells MDSCrepresent a heterogenic population of immature myeloid cells and are characterized by a strong ability to suppress various T cell functions. The molecular mechanism regulating MDSC differentiation includes many growth factorscytokines transcription factorsand several signaling pathways. These factors are critically important for the development of the effective therapeutic strategies to induce these cells in transplantation. Hereinwe briefly summarized the characterization of MDSCthe molecular mechanisms that regulate the development of MDSCand the role of MDSC in transplantation. Key words Myeloid-derived suppressor cells Regulation Immune tolerance Molecular biology 1 MDSC MDSC common myeloid progenitorcmp 20 80 CMP CMP myeloid-derived suppressor cellsmdsc MDSC MDSC MDSC DOI10. 3877 /cma. j. issn. 1647-3903. 2012. 02. 013 CD11b + Gr1 + 2010CB945301 81130055 100101 Emailzhaoy@ ioz. ac. cn Lin-HLA-DR-CD33 + CD11b + CD14 - CD33 + MDSC CD11b + Ly6G - Ly6C high CD11b + Ly6G + Ly6C low T
2012 5 6 2 Chin J Transplant Electronic Edition May 2012Vol 6No. 2 145 MDSC CMP MDSC G-CSF F4 /80 CD115 / G-CSF CD124 CD80 T MDSC MDSC G-CSF MDSC IL-6 3 IL-1β IL-17 κb 1 nuclear factor κb NF-κB 3-5 G-CSF T 2 3- T signal transducers and activators of transcription IL-10 TGF-β1 STAT3 MDSC 6 T MDSC 2. 1. 3 M-CSF NK M-CSF 2 MDSC M-CSF CD115 MDSC MDSC 7 M-CSF MDSC M-CSF MDSC M-CSF MDSC MDSC 8 MDSC 2. 1 MDSC granulocyte- MDSC 2. 1. 4 VEGF - VEGF 5 macrophage colony stimulating factorgm-csf VEGF granulocyte-colony stimulating factor G-CSF macrophagecolony stimulating factorm-csf 1 VEGF VEGF vascular endothelial growth factorvegf 2. 1. 1 GM-CSF NF-κB 11 GM-CSF VEGF 2 CD11b + CMP Gr1 + MDSC B 12 GM-CSF VEGF MDSC GM-CSF T 13 2. 2 MDSC GM-CSF MDSC 2. 2. 1 IL-1β 1 GM-CSF IL-1β IL-1β 2 GM-CSF IL-1β MDSC IL-10 M-CSF 9 Gr1 + B 10 MDSC 2. 1. 2 G-CSF IL-1β MDSC G-CSF 14 IL-1β 4T1
146 2012 5 6 2 Chin J Transplant Electronic Edition May 2012Vol 6No. 2 MDSC G 1 S IL-6 IL-1β C /EBPα CMP IL-6 MDSC 15 IL-1β 23 C /EBPβ MDSC IL-1 NF-κB MDSC 16 2. 2. 2 IL-6 MDSC C /EBPβ C /EBPβ CD11b + Gr1 + C /EBPβ MDSC IL-6 IL-6 C /EBPβ MDSC Arg1 CCAAT CCAAT / enhancer binding proteinsc /EBPβ C /EBP IL-6 GM-CSF MDSC NF-κB p50 17 C /EBPα 24 2. 2. 3 IFN-γ T 1 IFN-γ 2. 3. 2 PU. 1 IFN-γ - / - C /EBP PU. 1 T PU. 1 18 IFN-γ - CD11 F4 /80 25 IFN-γ CMP - MDSC IFN-γ PU. 1 CD11b - Gr1 + MDSC 19 PU. 1 26 MDSC C /EBPα PU. 1 IFN-γ 20 IFN-γ IFN-γ GM-CSF IL-6 M-CSF 27 MDSC MDSC IFN-γ 2. 3. 3 STAT MDSC Janus /STAT 21 IFN-γ MDSC T STAT3 22 2. 3 MDSC STAT3 STAT3 CMP CMP MDSC 28-29 MDSC STAT3 C /EBP PU. 1 STAT GM-CSF IL-6 MDSC C /EBPβ p50 G-CSF STAT1 STAT5 STAT6 MDSC MDSC MDSC STAT3 VEGF 2. 3. 1 C /EBP STAT3 30 C /EBP STAT3 C /EBPα MDSC 31 E2F1 STAT3
2012 5 6 2 Chin J Transplant Electronic Edition May 2012Vol 6No. 2 147 MDSC exosome 72 STAT3 MDSC 32 STAT3 MDSC STAT3 S100A9 S100A8 MDSC STAT3 MDSC MDSC CβⅡ STAT3 CβⅡ2. 4. 2 Notch MDSC MDSC Notch 35 STAT3 Notch1 RNA C /EBPβ C /EBPβ Notch MDSC 36 MDSC STAT3 STAT3 Notch 2 p47phox B 47 Notch gp91phox MDSC B 37 STAT3 MDSC 48 Notch MDSC STAT3 CXCL1 CXCL2 MDSC 38 STAT1 STAT5 STAT6 MDSC Wnt-β STAT1 IFN-γ IL-1β 49 β 1 MDSC STAT1 MDSC 1 β GM-CSF 1 T IL-4 CMP MDSC 50 CMP 39 STAT1 Wnt-β MDSC MDSC 40 STAT5 MDSC MDSC STAT6 IL-4 IL-13 CD124 CD124 MDSC MDSC 1 TGF-β1 STAT5 2. 5 MDSC T 41 STAT6 MDSC 42 MDSC 43 2. 4 MDSC S100A9 S100A8 2. 4. 1 NF-κB MDSC STAT3 NF-κB MDSC S100A9 S100A8 Toll IL-1R NF-κB MDSC MDSC S100A9 MDSC 44 NF-κB MDSC S100A9 33 C /EBPα MDSC MDSC Toll S100A9-S100A8 88 myeloid differentiation 88 NF-κB 1 triggering 33 receptor expressed on myeloid cells 1 S100A9 S100A8 MDSC N- NF-κB MDSC 45 88 MDSC MDSC 34 46 NF-κB 2. 4. 3 Wnt-β catenin MDSC 1
148 2012 5 6 2 Chin J Transplant Electronic Edition May 2012Vol 6No. 2 E 2 prostaglandin E 2 PGE 2 2cyclooxygenase-2 Cox2 p38 3- SH2 PPARγC SH2 domain containing 5'-inosi-tol phosphatase MDSC T 58 SHIP γ 2. 5. 4 RNA MDSC peroxisome proliferator-activated receptor-γpparγ RNA MDSC RNA MDSC CD11b + Gr1 + 2. 5. 1 PGE 2 Cox2 MDSC RNA MDSC PGE 2 MDSC T RNA mir-223 mir-17-5p mir-20a PGE 2 MDSC PGE 2 EP4 51 MDSC mir-223 MDSC PGE 2 MDSC 2 myocyte enhancer factor 2 Fas 3LL Lewis p38 PGE 2 MDSC MDSC STAT3 PEG 2 Cox2 MDSC MDSC 60 52 PGE 2 2 3 MDSC MDSC PGE 2 2 CD28 MDSC 53 MDSC MDSC PGE 2 Cox2 CD1a + CD14 + CD33 + CD34 + MDSC 54 MDSC PGE 2 61 CD40 Cox2 MDSC CD11b + Gr1 + CD115 + MDSC 20 55 IL-33 Cox2 PGE 2 MDSC IL-33 MDSC 62 2 / 2. 5. 2 SHIP MDSC HLA-G MDSC SHIP -3 4 5-2 -3 4-3- MDSC 2 MDSC 1 SHIP - / - 63 -N- MDSC Ⅲlacto-N-fucopentaose Ⅲ T 56 MDSC PD-L1 SHIP - / - 64 GM-CSF IL-13 57 MDSC 65 2. 5. 3 PPARγ MDSC STAT3 NF-κB Erk1 /2 MDSC mir-223 MDSC 59 mir-17-5p mir-20a PPARγ CD14 + CD14 - MDSC N- IL-1β IL-2 IL-6 - - T TNF-α IL-10 66 CMP - G-CSF MDSC PPARγ CD11b + Ly6G + T
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