Insights into Myeloid-Derived Suppressor Cells in Inflammatory Diseases

  • Yewon Kwak
  • Hye-Eun Kim
  • Sung Gyoo ParkEmail author


Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells involved in immune regulation. This population subdivides into granulocytic MDSCs and monocytic MDSCs, which regulate immune responses via the production of various molecules including reactive oxygen species, nitric oxide, arginase-1, interleukin-10, and transforming growth factor-β. Most studies of MDSCs focused on their role in tumors. MDSCs protect tumor cells from immune responses, and thus the frequency of MDSCs associates with poor prognosis. Many recent studies reported an important role for MDSCs in inflammatory diseases via the regulation of immune cells. In addition, the utilization of MDSCs by infectious pathogens suggests an immune evasion mechanism. Thus, MDSCs are important immune regulators in inflammatory diseases, as well as in tumors. This review focuses on the role of MDSCs in the regulation of inflammation in non-tumor settings.


Myeloid-derived suppressor cells Inflammation Autoimmunity Infection Transplantation 



This work was supported by grants from the Korean Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (Grant numbers: HI11C1791 and HI14C1466).


  1. Anthony DD et al (2011) Lower peripheral blood CD14+ monocyte frequency and higher CD34+ progenitor cell frequency are associated with HBV vaccine induced response in HIV infected individuals. Vaccine 29:3558–3563PubMedCentralPubMedGoogle Scholar
  2. Arakawa Y et al (2014) Cotransplantation with myeloid-derived suppressor cells protects cell transplants: a crucial role of inducible nitric oxide synthase. Transplantation 97:740–747PubMedCentralPubMedGoogle Scholar
  3. Arora M et al (2010) TLR4/MyD88-induced CD11b+Gr-1 int F4/80+ non-migratory myeloid cells suppress Th2 effector function in the lung. Mucosal Immunol 3:578–593PubMedCentralPubMedGoogle Scholar
  4. Arora M et al (2011) LPS-induced CD11b+Gr1(int)F4/80+ regulatory myeloid cells suppress allergen-induced airway inflammation. Int Immunopharmacol 11:827–832PubMedGoogle Scholar
  5. Baniyash M (2004) TCR zeta-chain downregulation: curtailing an excessive inflammatory immune response. Nat Rev Immunol 4:675–687PubMedGoogle Scholar
  6. Barnes PJ (2001) Th2 cytokines and asthma: an introduction. Respir Res 2:64–65PubMedCentralPubMedGoogle Scholar
  7. Bhushan V, Collins RH Jr (2003) Chronic graft-vs-host disease. JAMA 290:2599–2603PubMedGoogle Scholar
  8. Bingisser RM et al (1998) Macrophage-derived nitric oxide regulates T cell activation via reversible disruption of the Jak3/STAT5 signaling pathway. J Immunol 160:5729–5734PubMedGoogle Scholar
  9. Birrell MA et al (2005) Resveratrol, an extract of red wine, inhibits lipopolysaccharide induced airway neutrophilia and inflammatory mediators through an NF-kappaB-independent mechanism. FASEB J 19:840–841PubMedGoogle Scholar
  10. Bowen JL, Olson JK (2009) Innate immune CD11b+Gr-1+ cells, suppressor cells, affect the immune response during Theiler’s virus-induced demyelinating disease. J Immunol 183:6971–6980PubMedGoogle Scholar
  11. Braudeau C et al (2004) Induction of long-term cardiac allograft survival by heme oxygenase-1 gene transfer. Gene Ther 11:701–710PubMedGoogle Scholar
  12. Brito C et al (1999) Peroxynitrite inhibits T lymphocyte activation and proliferation by promoting impairment of tyrosine phosphorylation and peroxynitrite-driven apoptotic death. J Immunol 162:3356–3366PubMedGoogle Scholar
  13. Bunt SK et al (2009) Inflammation enhances myeloid-derived suppressor cell cross-talk by signaling through Toll-like receptor 4. J Leukoc Biol 85:996–1004PubMedCentralPubMedGoogle Scholar
  14. Burdette D et al (2012) Hepatitis C virus activates interleukin-1beta via caspase-1-inflammasome complex. J Gen Virol 93(Pt 2):235–246PubMedCentralPubMedGoogle Scholar
  15. Cai W et al (2013) Clinical significance and functional studies of myeloid-derived suppressor cells in chronic hepatitis C patients. J Clin Immunol 33:798–808PubMedGoogle Scholar
  16. Charles JF et al (2012) Inflammatory arthritis increases mouse osteoclast precursors with myeloid suppressor function. J Clin Invest 122:4592–4605PubMedCentralPubMedGoogle Scholar
  17. Chauveau C et al (2002) Gene transfer of heme oxygenase-1 and carbon monoxide delivery inhibit chronic rejection. Am J Transplant 2:581–592PubMedGoogle Scholar
  18. Chen S et al (2011) Immunosuppressive functions of hepatic myeloid-derived suppressor cells of normal mice and in a murine model of chronic hepatitis B virus. Clin Exp Immunol 166:134–142PubMedCentralPubMedGoogle Scholar
  19. Cheng P et al (2008) Inhibition of dendritic cell differentiation and accumulation of myeloid-derived suppressor cells in cancer is regulated by S100A9 protein. J Exp Med 205:2235–2249PubMedCentralPubMedGoogle Scholar
  20. Christ M et al (1994) Immune dysregulation in TGF-beta 1-deficient mice. J Immunol 153:1936–1946PubMedGoogle Scholar
  21. Corzo CA et al (2009) Mechanism regulating reactive oxygen species in tumor-induced myeloid-derived suppressor cells. J Immunol 182:5693–5701PubMedCentralPubMedGoogle Scholar
  22. Cripps JG, Gorham JD (2011) MDSC in autoimmunity. Int Immunopharmacol 11:789–793Google Scholar
  23. Cripps JG et al (2010) Type 1 T helper cells induce the accumulation of myeloid-derived suppressor cells in the inflamed Tgfb1 knockout mouse liver. Hepatology 52:1350–1359PubMedCentralPubMedGoogle Scholar
  24. Croxford AL et al (2011) Mouse models for multiple sclerosis: historical facts and future implications. Biochim Biophys Acta 1812:177–183PubMedGoogle Scholar
  25. De Santo C et al (2008) Invariant NKT cells reduce the immunosuppressive activity of influenza A virus-induced myeloid-derived suppressor cells in mice and humans. J Clin Invest 118:4036–4048PubMedCentralPubMedGoogle Scholar
  26. De Wilde V et al (2009) Endotoxin-induced myeloid-derived suppressor cells inhibit alloimmune responses via heme oxygenase-1. Am J Transplant 9:2034–2047PubMedGoogle Scholar
  27. Delano MJ et al (2007) MyD88-dependent expansion of an immature GR-1(+)CD11b(+) population induces T cell suppression and Th2 polarization in sepsis. J Exp Med 204:1463–1474PubMedCentralPubMedGoogle Scholar
  28. Deshane J et al (2011) Free radical-producing myeloid-derived regulatory cells: potent activators and suppressors of lung inflammation and airway hyperresponsiveness. Mucosal Immunol 4:503–518PubMedCentralPubMedGoogle Scholar
  29. Dietlin TA et al (2007) Mycobacteria-induced Gr-1+ subsets from distinct myeloid lineages have opposite effects on T cell expansion. J Leukoc Biol 81:1205–1212PubMedGoogle Scholar
  30. Dilek N et al (2012) Control of transplant tolerance and intragraft regulatory T cell localization by myeloid-derived suppressor cells and CCL5. J Immunol 188:4209–4216PubMedGoogle Scholar
  31. Djukanovic R et al (1990) Mucosal inflammation in asthma. Am Rev Respir Dis 142:434–457PubMedGoogle Scholar
  32. Dong C (2008) TH17 cells in development: an updated view of their molecular identity and genetic programming. Nat Rev Immunol 8:337–348PubMedGoogle Scholar
  33. Drujont L et al (2014) Evaluation of the therapeutic potential of bone marrow-derived myeloid suppressor cell (MDSC) adoptive transfer in mouse models of autoimmunity and allograft rejection. PLoS One 9:e100013PubMedCentralPubMedGoogle Scholar
  34. Dugast AS et al (2008) Myeloid-derived suppressor cells accumulate in kidney allograft tolerance and specifically suppress effector T cell expansion. J Immunol 180:7898–7906PubMedGoogle Scholar
  35. Egelston C et al (2012) Suppression of dendritic cell maturation and T cell proliferation by synovial fluid myeloid cells from mice with autoimmune arthritis. Arthritis Rheum 64:3179–3188PubMedCentralPubMedGoogle Scholar
  36. Ekmekcioglu S et al (2000) Inducible nitric oxide synthase and nitrotyrosine in human metastatic melanoma tumors correlate with poor survival. Clin Cancer Res 6:4768–4775PubMedGoogle Scholar
  37. Elkabets M et al (2010) IL-1beta regulates a novel myeloid-derived suppressor cell subset that impairs NK cell development and function. Eur J Immunol 40:3347–3357PubMedCentralPubMedGoogle Scholar
  38. Elmali N et al (2005) Effect of resveratrol in experimental osteoarthritis in rabbits. Inflamm Res 54:158–162PubMedGoogle Scholar
  39. Enioutina EY et al (2011) A role for immature myeloid cells in immune senescence. J Immunol 186:697–707PubMedGoogle Scholar
  40. Fagundes CT et al (2007) ST2, an IL-1R family member, attenuates inflammation and lethality after intestinal ischemia and reperfusion. J Leukoc Biol 81:492–499PubMedGoogle Scholar
  41. Farrell AJ et al (1992) Increased concentrations of nitrite in synovial fluid and serum samples suggest increased nitric oxide synthesis in rheumatic diseases. Ann Rheum Dis 51:1219–1222PubMedCentralPubMedGoogle Scholar
  42. Fu B et al (2014) Subsets of human natural killer cells and their regulatory effects. Immunology 141:483–489PubMedCentralPubMedGoogle Scholar
  43. Fujii W et al (2013) Myeloid-derived suppressor cells play crucial roles in the regulation of mouse collagen-induced arthritis. J Immunol 191:1073–1081PubMedGoogle Scholar
  44. Gabrilovich DI, Nagaraj S (2009) Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 9:162–174PubMedCentralPubMedGoogle Scholar
  45. Gabrilovich DI et al (2001) Mechanism of immune dysfunction in cancer mediated by immature Gr-1 + myeloid cells. J Immunol 166:5398–5406PubMedGoogle Scholar
  46. Gantt S et al (2014) The role of myeloid-derived suppressor cells in immune ontogeny. Front Immunol 5:387PubMedCentralPubMedGoogle Scholar
  47. Garg A, Spector SA (2014) HIV type 1 gp120-induced expansion of myeloid derived suppressor cells is dependent on interleukin 6 and suppresses immunity. J Infect Dis 209:441–451PubMedCentralPubMedGoogle Scholar
  48. Gaupp S et al (2003) Experimental autoimmune encephalomyelitis (EAE) in CCR2(−/−) mice: susceptibility in multiple strains. Am J Pathol 162:139–150PubMedCentralPubMedGoogle Scholar
  49. Gervassi A et al (2014) Myeloid derived suppressor cells are present at high frequency in neonates and suppress in vitro T cell responses. PLoS One 9:e107816PubMedCentralPubMedGoogle Scholar
  50. Goh C et al (2013) Myeloid-derived suppressor cells: the dark knight or the joker in viral infections? Immunol Rev 255:210–221PubMedCentralPubMedGoogle Scholar
  51. Goker H et al (2001) Acute graft-vs-host disease: pathobiology and management. Exp Hematol 29:259–277PubMedGoogle Scholar
  52. Gorham JD et al (2001) Genetic regulation of autoimmune disease: bALB/c background TGF-beta 1-deficient mice develop necroinflammatory IFN-gamma-dependent hepatitis. J Immunol 166:6413–6422PubMedGoogle Scholar
  53. Greifenberg V et al (2009) Myeloid-derived suppressor cell activation by combined LPS and IFN-gamma treatment impairs DC development. Eur J Immunol 39:2865–2876PubMedGoogle Scholar
  54. Guan Q et al (2013) The role and potential therapeutic application of myeloid-derived suppressor cells in TNBS-induced colitis. J Leukoc Biol 94:803–811PubMedGoogle Scholar
  55. Haile LA et al (2008) Myeloid-derived suppressor cells in inflammatory bowel disease: a new immunoregulatory pathway. Gastroenterology 135:871–881 (881 e871–875) PubMedGoogle Scholar
  56. Haile LA et al (2010) CD49d is a new marker for distinct myeloid-derived suppressor cell subpopulations in mice. J Immunol 185:203–210PubMedGoogle Scholar
  57. Hamid Q, Tulic M (2009) Immunobiology of asthma. Ann Rev Physiol 71:489–507Google Scholar
  58. Harari O, Liao JK (2004) Inhibition of MHC II gene transcription by nitric oxide and antioxidants. Curr Pharm Des 10:893–898PubMedCentralPubMedGoogle Scholar
  59. Haspot F et al (2005) Anti-CD28 antibody-induced kidney allograft tolerance related to tryptophan degradation and TCR class II B7 regulatory cells. Am J Transplant 5:2339–2348PubMedGoogle Scholar
  60. Hoechst B et al (2009) Myeloid derived suppressor cells inhibit natural killer cells in patients with hepatocellular carcinoma via the NKp30 receptor. Hepatology 50:799–807PubMedGoogle Scholar
  61. Hsieh CC et al (2013) The role of complement component 3 (C3) in differentiation of myeloid-derived suppressor cells. Blood 121:1760–1768PubMedCentralPubMedGoogle Scholar
  62. Huang B et al (2006) Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host. Cancer Res 66:1123–1131PubMedGoogle Scholar
  63. Iwata Y et al (2010) Involvement of CD11b+ GR-1 low cells in autoimmune disorder in MRL-Fas lpr mouse. Clin Exp Nephrol 14:411–417PubMedGoogle Scholar
  64. Jiang J et al (2014) Phenotypes, accumulation, and functions of myeloid-derived suppressor cells and associated treatment strategies in cancer patients. Hum Immunol 75:1128–1137PubMedGoogle Scholar
  65. Jiao Z et al (2013) Increased circulating myeloid-derived suppressor cells correlated negatively with Th17 cells in patients with rheumatoid arthritis. Scand J Rheumatol 42:85–90PubMedGoogle Scholar
  66. Kanazawa S et al (2000) Tat competes with CIITA for the binding to P-TEFb and blocks the expression of MHC class II genes in HIV infection. Immunity 12:61–70PubMedGoogle Scholar
  67. Katoh H et al (2013) CXCR2-expressing myeloid-derived suppressor cells are essential to promote colitis-associated tumorigenesis. Cancer Cell 24:631–644PubMedCentralPubMedGoogle Scholar
  68. Kerr EC et al (2008) Analysis of retinal cellular infiltrate in experimental autoimmune uveoretinitis reveals multiple regulatory cell populations. J Autoimmun 31:354–361PubMedGoogle Scholar
  69. Khaled YS et al (2013) Myeloid-derived suppressor cells in cancer: recent progress and prospects. Immunol Cell Biol 91:493–502PubMedGoogle Scholar
  70. Kim YJ et al (2011) Phagocytosis, a potential mechanism for myeloid-derived suppressor cell regulation of CD8+ T cell function mediated through programmed cell death-1 and programmed cell death-1 ligand interaction. J Immunol 187:2291–2301PubMedCentralPubMedGoogle Scholar
  71. King IL et al (2009) Circulating Ly-6C+ myeloid precursors migrate to the CNS and play a pathogenic role during autoimmune demyelinating disease. Blood 113:3190–3197PubMedCentralPubMedGoogle Scholar
  72. Kinnula VL et al (2004) Ultrastructural and chromosomal studies on manganese superoxide dismutase in malignant mesothelioma. Am J Respir Cell Mol Biol 31:147–153PubMedGoogle Scholar
  73. Ko HJ et al (2009) Immunosuppressive myeloid-derived suppressor cells can be converted into immunogenic APCs with the help of activated NKT cells: an alternative cell-based antitumor vaccine. J Immunol 182:1818–1828PubMedGoogle Scholar
  74. Kobayashi M et al (2008) Gr-1(+)CD11b(+) cells as an accelerator of sepsis stemming from Pseudomonas aeruginosa wound infection in thermally injured mice. J Leukoc Biol 83:1354–1362PubMedGoogle Scholar
  75. Kong X et al (2014) gammadeltaT cells drive myeloid-derived suppressor cell-mediated CD8+ T cell exhaustion in hepatitis B virus-induced immunotolerance. J Immunol 193:1645–1653PubMedGoogle Scholar
  76. Krawitt EL (2006) Autoimmune hepatitis. N Engl J Med 354:54–66PubMedGoogle Scholar
  77. Kropf P et al (2007) Arginase activity mediates reversible T cell hyporesponsiveness in human pregnancy. Eur J Immunol 37:935–945PubMedCentralPubMedGoogle Scholar
  78. Kurko J et al (2014) Identification of myeloid-derived suppressor cells in the synovial fluid of patients with rheumatoid arthritis: a pilot study. BMC Musculoskelet Disord 15:281PubMedCentralPubMedGoogle Scholar
  79. Kusmartsev S, Gabrilovich DI (2003) Inhibition of myeloid cell differentiation in cancer: the role of reactive oxygen species. J Leukoc Biol 74:186–196PubMedGoogle Scholar
  80. Kusmartsev S et al (2005) Tumor-associated CD8+ T cell tolerance induced by bone marrow-derived immature myeloid cells. J Immunol 175:4583–4592PubMedCentralPubMedGoogle Scholar
  81. Lapinski TW (2001) The levels of IL-1beta, IL-4 and IL-6 in the serum and the liver tissue of chronic HCV-infected patients. Arch Immunol Ther Exp 49:311–316Google Scholar
  82. Le Blanc K et al (2013) Myeloid-derived suppressor cells in allogeneic hematopoietic stem cell transplantation: a double-edged sword? Oncoimmunology 2:e25009PubMedCentralPubMedGoogle Scholar
  83. Lechler R et al (2001) Dendritic cells in transplantation—friend or foe? Immunity 14:357–368PubMedGoogle Scholar
  84. Lee CH et al (2001) Hepatitis C virus core protein inhibits interleukin 12 and nitric oxide production from activated macrophages. Virology 279:271–279PubMedGoogle Scholar
  85. LeMaoult J et al (2004) HLA-G1-expressing antigen-presenting cells induce immunosuppressive CD4+ T cells. Proc Natl Acad Sci USA 101:7064–7069PubMedCentralPubMedGoogle Scholar
  86. LeMaoult J et al (2005) HLA-G up-regulates ILT2, ILT3, ILT4, and KIR2DL4 in antigen presenting cells, NK cells, and T cells. FASEB J 19:662–664PubMedGoogle Scholar
  87. Li H et al (2009) Cancer-expanded myeloid-derived suppressor cells induce anergy of NK cells through membrane-bound TGF-beta 1. J Immunol 182:240–249PubMedGoogle Scholar
  88. Liang S et al (2008) Modulation of dendritic cell differentiation by HLA-G and ILT4 requires the IL-6–STAT3 signaling pathway. Proc Natl Acad Sci USA 105:8357–8362PubMedCentralPubMedGoogle Scholar
  89. Liu C et al (2007) Expansion of spleen myeloid suppressor cells represses NK cell cytotoxicity in tumor-bearing host. Blood 109:4336–4342PubMedCentralPubMedGoogle Scholar
  90. Liu C et al (2011) Poly(I:C) induce bone marrow precursor cells into myeloid-derived suppressor cells. Mol Cell Biochem 358:317–323PubMedGoogle Scholar
  91. Lu T et al (2011) Tumor-infiltrating myeloid cells induce tumor cell resistance to cytotoxic T cells in mice. J Clin Invest 121:4015–4029PubMedCentralPubMedGoogle Scholar
  92. Luan Y et al (2013) Monocytic myeloid-derived suppressor cells accumulate in renal transplant patients and mediate CD4(+) Foxp3(+) Treg expansion. Am J Transplant 13:3123–3131PubMedGoogle Scholar
  93. Lv M et al (2015) Monocytic and promyelocytic myeloid-derived suppressor cells may contribute to G-CSF-induced immune tolerance in haplo-identical allogeneic hematopoietic stem cell transplantation. Am J Hematol 90:E9–E16PubMedGoogle Scholar
  94. Macatangay BJ et al (2012) MDSC: a new player in HIV immunopathogenesis. AIDS 26:1567–1569PubMedCentralPubMedGoogle Scholar
  95. Marhaba R et al (2007) The importance of myeloid-derived suppressor cells in the regulation of autoimmune effector cells by a chronic contact eczema. J Immunol 179:5071–5081PubMedGoogle Scholar
  96. Markowitz J et al (2013) Myeloid-derived suppressor cells in breast cancer. Breast Cancer Res Treat 140:13–21PubMedCentralPubMedGoogle Scholar
  97. McIntosh KR, Drachman DB (1999) Induction of apoptosis in activated T cell blasts by suppressive macrophages: a possible immunotherapeutic approach for treatment of autoimmune disease. Cell Immunol 193:24–35PubMedGoogle Scholar
  98. Mencacci A et al (2002) CD80+Gr-1+ myeloid cells inhibit development of antifungal Th1 immunity in mice with candidiasis. J Immunology 169:3180–3190Google Scholar
  99. Mildner A et al (2009) CCR2+ Ly-6Chi monocytes are crucial for the effector phase of autoimmunity in the central nervous system. Brain 132:2487–2500PubMedGoogle Scholar
  100. Modolell M et al (1995) Reciprocal regulation of the nitric oxide synthase/arginase balance in mouse bone marrow-derived macrophages by TH1 and TH2 cytokines. Eur J Immunol 25:1101–1104PubMedGoogle Scholar
  101. Movahedi K et al (2008) Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cell-suppressive activity. Blood 111:4233–4244PubMedGoogle Scholar
  102. Nagaraj S et al (2007) Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer. Nat Med 13:828–835PubMedCentralPubMedGoogle Scholar
  103. Nagaraj S et al (2010) Mechanism of T cell tolerance induced by myeloid-derived suppressor cells. J Immunol 184:3106–3116PubMedCentralPubMedGoogle Scholar
  104. Nakamura Y et al (2006) Nitric oxide in breast cancer: induction of vascular endothelial growth factor-C and correlation with metastasis and poor prognosis. Clin Cancer Res 12:1201–1207PubMedGoogle Scholar
  105. Nausch N et al (2008) Mononuclear myeloid-derived “suppressor” cells express RAE-1 and activate natural killer cells. Blood 112:4080–4089PubMedCentralPubMedGoogle Scholar
  106. Nguyen H et al (2006) Hepatitis C virus core protein induces expression of genes regulating immune evasion and anti-apoptosis in hepatocytes. Virology 354:58–68PubMedGoogle Scholar
  107. Noel JG et al (2005) Effect of thermal injury on splenic myelopoiesis. Shock 23:115–122PubMedGoogle Scholar
  108. Noel JG et al (2007) Thermal injury elevates the inflammatory monocyte subpopulation in multiple compartments. Shock 28:684–693PubMedGoogle Scholar
  109. Obermajer N et al (2011) Positive feedback between PGE2 and COX2 redirects the differentiation of human dendritic cells toward stable myeloid-derived suppressor cells. Blood 118:5498–5505PubMedCentralPubMedGoogle Scholar
  110. Olson JK et al (2001) Direct activation of innate and antigen-presenting functions of microglia following infection with Theiler’s virus. J Virol 75:9780–9789PubMedCentralPubMedGoogle Scholar
  111. Ostanin DV, Bhattacharya D (2013) Myeloid-derived suppressor cells in the inflammatory bowel diseases. Inflamm Bowel Dis 19:2468–2477PubMedGoogle Scholar
  112. Ostrand-Rosenberg S (2010) Myeloid-derived suppressor cells: more mechanisms for inhibiting antitumor immunity. Cancer Immunol Immunother 59:1593–1600PubMedCentralPubMedGoogle Scholar
  113. Ostrand-Rosenberg S, Sinha P (2009) Myeloid-derived suppressor cells: linking inflammation and cancer. J Immunol 182:4499–4506PubMedCentralPubMedGoogle Scholar
  114. Ostrand-Rosenberg S et al (2012) Cross-talk between myeloid-derived suppressor cells (MDSC), macrophages, and dendritic cells enhances tumor-induced immune suppression. Semin Cancer Biol 22:275–281PubMedCentralPubMedGoogle Scholar
  115. Pak AS et al (1995) Mechanisms of immune suppression in patients with head and neck cancer: presence of CD34(+) cells which suppress immune functions within cancers that secrete granulocyte-macrophage colony-stimulating factor. Clin Cancer Res 1:95–103PubMedGoogle Scholar
  116. Poe SL et al (2013) STAT1-regulated lung MDSC-like cells produce IL-10 and efferocytose apoptotic neutrophils with relevance in resolution of bacterial pneumonia. Mucosal Immunol 6:189–199PubMedCentralPubMedGoogle Scholar
  117. Popovic PJ et al (2007) Arginine and immunity. J Nutr 137:1681S–1686SPubMedGoogle Scholar
  118. Pulendran B et al (2010) Programming dendritic cells to induce T(H)2 and tolerogenic responses. Nat Immunol 11:647–655PubMedGoogle Scholar
  119. Qin A et al (2013) Expansion of monocytic myeloid-derived suppressor cells dampens T cell function in HIV-1-seropositive individuals. J Virol 87:1477–1490PubMedCentralPubMedGoogle Scholar
  120. Rajagopalan S, Long EO (2005) Viral evasion of NK-cell activation. Trends Immunol 26:403–405PubMedGoogle Scholar
  121. Raveney BJ et al (2009) TNFR1-dependent regulation of myeloid cell function in experimental autoimmune uveoretinitis. J Immunol 183:2321–2329PubMedGoogle Scholar
  122. Rieber N et al (2013) Neutrophilic myeloid-derived suppressor cells in cord blood modulate innate and adaptive immune responses. Clin Exp Immunol 174:45–52PubMedCentralPubMedGoogle Scholar
  123. Ristich V et al (2005) Tolerization of dendritic cells by HLA-G. Eur J Immunol 35:1133–1142PubMedGoogle Scholar
  124. Roder J, Hickey WF (1996) Mouse models, immunology, multiple sclerosis and myelination. Nat Genet 12:6–8PubMedGoogle Scholar
  125. Rodriguez D et al (2003) Bacterial lipopolysaccharide signaling through Toll-like receptor 4 suppresses asthma-like responses via nitric oxide synthase 2 activity. J Immunol 171:1001–1008PubMedGoogle Scholar
  126. Rodriguez PC et al (2004) Arginase I production in the tumor microenvironment by mature myeloid cells inhibits T-cell receptor expression and antigen-specific T-cell responses. Cancer Res 64:5839–5849PubMedGoogle Scholar
  127. Rodriguez PC et al (2007) L-arginine availability regulates T-lymphocyte cell-cycle progression. Blood 109:1568–1573PubMedCentralPubMedGoogle Scholar
  128. Rudner LA et al (2003) Necroinflammatory liver disease in BALB/c background, TGF-beta 1-deficient mice requires CD4+ T cells. J Immunol 170:4785–4792PubMedGoogle Scholar
  129. Sakaguchi N et al (2003) Altered thymic T-cell selection due to a mutation of the ZAP-70 gene causes autoimmune arthritis in mice. Nature 426:454–460PubMedGoogle Scholar
  130. Schwacha MG et al (2010) Impact of thermal injury on wound infiltration and the dermal inflammatory response. J Surg Res 158:112–120PubMedCentralPubMedGoogle Scholar
  131. Senaldi G et al (1992) Immunohistochemical features of the portal tract mononuclear cell infiltrate in chronic aggressive hepatitis. Arch Dis Child 67:1447–1453PubMedCentralPubMedGoogle Scholar
  132. Serafini P et al (2008) Myeloid-derived suppressor cells promote cross-tolerance in B-cell lymphoma by expanding regulatory T cells. Cancer Res 68:5439–5449PubMedCentralPubMedGoogle Scholar
  133. Shi M et al (2014) Myeloid-derived suppressor cell function is diminished in aspirin-triggered allergic airway hyperresponsiveness in mice. J Allergy Clin Immunol 134(1163–1174):e16PubMedGoogle Scholar
  134. Shull MM et al (1992) Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature 359:693–699PubMedCentralPubMedGoogle Scholar
  135. Singh NP et al (2007) Resveratrol (trans-3,5,4′-trihydroxystilbene) ameliorates experimental allergic encephalomyelitis, primarily via induction of apoptosis in T cells involving activation of aryl hydrocarbon receptor and estrogen receptor. Mol Pharmacol 72:1508–1521PubMedGoogle Scholar
  136. Singh UP et al (2010) Resveratrol (trans-3,5,4′-trihydroxystilbene) induces silent mating type information regulation-1 and down-regulates nuclear transcription factor-kappaB activation to abrogate dextran sulfate sodium-induced colitis. J Pharmacol Exp Ther 332:829–839PubMedCentralPubMedGoogle Scholar
  137. Singh UP et al (2012) Role of resveratrol-induced CD11b(+) Gr-1(+) myeloid derived suppressor cells (MDSCs) in the reduction of CXCR3(+) T cells and amelioration of chronic colitis in IL-10(−/−) mice. Brain Behav Immun 26:72–82PubMedCentralPubMedGoogle Scholar
  138. Sinha P et al (2007) Cross-talk between myeloid-derived suppressor cells and macrophages subverts tumor immunity toward a type 2 response. J Immunol 179:977–983PubMedGoogle Scholar
  139. Smolen JS, Aletaha D (2015) Rheumatoid arthritis therapy reappraisal: strategies, opportunities and challenges. Nat Rev Rheumatol 11:276–289PubMedGoogle Scholar
  140. Soares MP et al (1998) Expression of heme oxygenase-1 can determine cardiac xenograft survival. Nat Med 4:1073–1077PubMedGoogle Scholar
  141. Song C et al (2014) Passive transfer of tumour-derived MDSCs inhibits asthma-related airway inflammation. Scand J Immunol 79:98–104PubMedGoogle Scholar
  142. Su H et al (2013) Transplantation of granulocytic myeloid-derived suppressor cells (G-MDSCs) could reduce colitis in experimental murine models. J Digestive Dis 14:251–258Google Scholar
  143. Sui Y et al (2014) Vaccine-induced myeloid cell population dampens protective immunity to SIV. J Clin Invest 124:2538–2549PubMedCentralPubMedGoogle Scholar
  144. Sunthamala N et al (2014) HPV16 E2 protein promotes innate immunity by modulating immunosuppressive status. Biochem Biophys Res Commun 446:977–982PubMedGoogle Scholar
  145. Suzuki E et al (2005) Gemcitabine selectively eliminates splenic Gr-1+/CD11b+ myeloid suppressor cells in tumor-bearing animals and enhances antitumor immune activity. Clin Cancer Res 11:6713–6721PubMedGoogle Scholar
  146. Tacke RS et al (2011) Extracellular hepatitis C virus core protein activates STAT3 in human monocytes/macrophages/dendritic cells via an IL-6 autocrine pathway. J Biol Chem 286:10847–10855PubMedCentralPubMedGoogle Scholar
  147. Torres-Aguilar H et al (2010) Tolerogenic dendritic cells in autoimmune diseases: crucial players in induction and prevention of autoimmunity. Autoimmun Rev 10:8–17PubMedGoogle Scholar
  148. Tsuchihashi S et al (2007) Heme oxygenase-1 mediated cytoprotection against liver ischemia and reperfusion injury: inhibition of type-1 interferon signaling. Transplantation 83:1628–1634PubMedGoogle Scholar
  149. Tu S et al (2008) Overexpression of interleukin-1beta induces gastric inflammation and cancer and mobilizes myeloid-derived suppressor cells in mice. Cancer Cell 14:408–419PubMedCentralPubMedGoogle Scholar
  150. Turnquist HR et al (2011) IL-33 expands suppressive CD11b+Gr-1(int) and regulatory T cells, including ST2L+ Foxp3+ cells, and mediates regulatory T cell-dependent promotion of cardiac allograft survival. J Immunol 187:4598–4610PubMedCentralPubMedGoogle Scholar
  151. Vaknin I et al (2008) A common pathway mediated through Toll-like receptors leads to T- and natural killer-cell immunosuppression. Blood 111:1437–1447PubMedGoogle Scholar
  152. Van Ginderachter JA et al (2010) Myeloid-derived suppressor cells in parasitic infections. Eur J Immunol 40:2976–2985PubMedGoogle Scholar
  153. Vendramin A et al (2014) Graft monocytic myeloid-derived suppressor cell content predicts the risk of acute graft-versus-host disease after allogeneic transplantation of granulocyte colony-stimulating factor-mobilized peripheral blood stem cells. Biol Blood Marrow Transplant 20:2049–2055PubMedGoogle Scholar
  154. Vickers SM et al (1999) Association of increased immunostaining for inducible nitric oxide synthase and nitrotyrosine with fibroblast growth factor transformation in pancreatic cancer. Arch Surg 134:245–251PubMedGoogle Scholar
  155. Vollbrecht T et al (2012) Chronic progressive HIV-1 infection is associated with elevated levels of myeloid-derived suppressor cells. AIDS 26:F31–F37PubMedGoogle Scholar
  156. Wang Y et al (2012) Myeloid-derived suppressor cells participate in preventing graft rejection. Clin Dev Immunol 2012:731486PubMedCentralPubMedGoogle Scholar
  157. Wang D et al (2013) Dynamic change and impact of myeloid-derived suppressor cells in allogeneic bone marrow transplantation in mice. Biol Blood Marrow Transplant 19:692–702PubMedCentralPubMedGoogle Scholar
  158. Wang W et al (2015) Functional characterization of myeloid-derived suppressor cell subpopulations during the development of experimental arthritis. Eur J Immunol 45:464–473PubMedGoogle Scholar
  159. Westendorf AM et al (2006) Autoimmune-mediated intestinal inflammation-impact and regulation of antigen-specific CD8 + T cells. Gastroenterology 131:510–524PubMedGoogle Scholar
  160. Wu T et al (2012) Smad3-deficient CD11b(+)Gr1(+) myeloid-derived suppressor cells prevent allograft rejection via the nitric oxide pathway. J Immunol 189:4989–5000PubMedGoogle Scholar
  161. Wu T et al (2014) The roles of myeloid-derived suppressor cells in transplantation. Expert Rev Clin Immunol 10:1385–1394PubMedGoogle Scholar
  162. Yamashita K et al (2006) Heme oxygenase-1 is essential for and promotes tolerance to transplanted organs. FASEB J 20:776–778PubMedGoogle Scholar
  163. Yang R et al (2006) CD80 in immune suppression by mouse ovarian carcinoma-associated Gr-1+CD11b1+ myeloid cells. Cancer Res 66:6807–6815PubMedGoogle Scholar
  164. Yao ZQ et al (2003) HCV core/gC1qR interaction arrests T cell cycle progression through stabilization of the cell cycle inhibitor p27Kip1. Virology 314:271–282PubMedGoogle Scholar
  165. Yao ZQ et al (2004) Direct binding of hepatitis C virus core to gC1qR on CD4+ and CD8+ T cells leads to impaired activation of Lck and Akt. J Virol 78:6409–6419PubMedCentralPubMedGoogle Scholar
  166. Yi H et al (2012) Mouse CD11b+Gr-1+ myeloid cells can promote Th17 cell differentiation and experimental autoimmune encephalomyelitis. J Immunol 189:4295–4304PubMedCentralPubMedGoogle Scholar
  167. Yin B et al (2010) Myeloid-derived suppressor cells prevent type 1 diabetes in murine models. J Immunol 185:5828–5834PubMedCentralPubMedGoogle Scholar
  168. Youn JI, Gabrilovich DI (2010) The biology of myeloid-derived suppressor cells: the blessing and the curse of morphological and functional heterogeneity. Eur J Immunol 40:2969–2975PubMedCentralPubMedGoogle Scholar
  169. Young MR, Newby M, Wepsic HT (1987) Hematopoiesis and suppressor bone marrow cells in mice bearing large metastatic Lewis lung carcinoma tumors. Cancer Res 47:100–105PubMedGoogle Scholar
  170. Zhang W et al (2008) Human inhibitory receptor immunoglobulin-like transcript 2 amplifies CD11b+Gr1+ myeloid-derived suppressor cells that promote long-term survival of allografts. Transplantation 86:1125–1134PubMedCentralPubMedGoogle Scholar
  171. Zhang R et al (2011a) Up-regulation of Gr1+CD11b+ population in spleen of dextran sulfate sodium administered mice works to repair colitis. Inflamm Allergy Drug Targets 10:39–46PubMedGoogle Scholar
  172. Zhang R et al (2011b) Dextran sulphate sodium increases splenic Gr1(+)CD11b(+) cells which accelerate recovery from colitis following intravenous transplantation. Clin Exp Immunol 164:417–427PubMedCentralPubMedGoogle Scholar
  173. Zhang YL et al (2013) Peripheral blood MDSCs, IL-10 and IL-12 in children with asthma and their importance in asthma development. PLoS One 8:e63775PubMedCentralPubMedGoogle Scholar
  174. Zhang L et al (2014) Myeloid-derived suppressor cells protect mouse models from autoimmune arthritis via controlling inflammatory response. Inflammation 37:670–677PubMedGoogle Scholar
  175. Zhao X et al (2012) TNF signaling drives myeloid-derived suppressor cell accumulation. J Clin Invest 122:4094–4104PubMedCentralPubMedGoogle Scholar
  176. Zhong H et al (2014) Origin and pharmacological modulation of tumor-associated regulatory dendritic cells. J Int Cancer 134:2633–2645Google Scholar
  177. Zhu B et al (2007) CD11b+Ly-6C(hi) suppressive monocytes in experimental autoimmune encephalomyelitis. J Immunol 179:5228–5237PubMedGoogle Scholar
  178. Zhu J et al (2012) Myeloid-derived suppressor cells regulate natural killer cell response to adenovirus-mediated gene transfer. J Virol 86:13689–13696PubMedCentralPubMedGoogle Scholar
  179. Zhu XJ et al (2013) Amplification of functional myeloid-derived suppressor cells during stem cell mobilization induced by granulocyte colony-stimulation-factor. J Huazhong Univ Sci Technolog Med Sci 33:817–821PubMedGoogle Scholar

Copyright information

© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2015

Authors and Affiliations

  1. 1.School of Life SciencesGwangju Institute of Science and Technology (GIST)GwangjuRepublic of Korea

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