Skip to main content

Advertisement

SpringerLink
Log in

Role of Myeloid-derived suppressor cell (MDSC) in autoimmunity and its potential as a therapeutic target

  • Review
  • Published:
Inflammopharmacology Aims and scope Submit manuscript

Abstract

Myeloid suppressor cells (MDSCs) are an important class of immune-regulating cells that can suppress T cell function. Most of our knowledge about the function of MDSC comes from studies of cancer models. Recent studies, however, have greatly contributed to the description of MDSC involvement in autoimmune diseases. They are known as a cell population that may negatively affect immune responses by regulating the function of CD4+ and CD8+ cells, which makes them an attractive target for autoimmune diseases therapy. However, many questions about MDSC activation, differentiation, and inhibitory functions remain unanswered. In this study, we have summarized the role of MDSCs in various autoimmune diseases, and the potential of targeting them for therapeutic benefits has been discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Ahluwalia B, Moraes L, Magnusson MK, Öhman L (2018) Immunopathogenesis of inflammatory bowel disease and mechanisms of biological therapies. Scand J Gastroenterol 53(4):379–389

    Article  PubMed  Google Scholar 

  • Akil AA-S, Yassin E, Al-Maraghi A, Aliyev E, Al-Malki K, Fakhro KA (2021) Diagnosis and treatment of type 1 diabetes at the dawn of the personalized medicine era. J Transl Med 19(1):137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boros P, Ochando J, Zeher M (2016) Myeloid derived suppressor cells and autoimmunity. Hum Immunol 77(8):631–636

    Article  CAS  PubMed  Google Scholar 

  • Bronte V, Brandau S, Chen S-H, Colombo MP, Frey AB, Greten TF et al (2016) Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards. Nat Commun. https://doi.org/10.1038/ncomms12150

    Article  PubMed  PubMed Central  Google Scholar 

  • Buessow SC, Paul RD, Lopez DM (1984) Influence of mammary tumor progression on phenotype and function of spleen and in situ lymphocytes in mice. J Natl Cancer Inst 73(1):249–255

    CAS  PubMed  Google Scholar 

  • Carlos D, Costa FR, Pereira CA, Rocha FA, Yaochite JN, Oliveira GG et al (2017) Mitochondrial DNA activates the NLRP3 inflammasome and predisposes to type 1 diabetes in murine model. Front Immunol 8:164

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cassetta L, Baekkevold ES, Brandau S, Bujko A, Cassatella MA, Dorhoi A et al (2019) Deciphering myeloid-derived suppressor cells: isolation and markers in humans, mice and non-human primates. Cancer Immunol Immunother: CII 68(4):687–697

    Article  CAS  PubMed  Google Scholar 

  • Chou HS, Hsieh CC, Yang HR, Wang L, Arakawa Y, Brown K et al (2011) Hepatic stellate cells regulate immune response by way of induction of myeloid suppressor cells in mice. Hepatology 53(3):1007–1019

    Article  CAS  PubMed  Google Scholar 

  • Chou HS, Hsieh CC, Charles R, Wang L, Wagner T, Fung JJ et al (2012) Myeloid-derived suppressor cells protect islet transplants by B7–H1 mediated enhancement of T regulatory cells. Transplantation 93(3):272–282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Condamine T, Dominguez GA, Youn J-I, Kossenkov AV, Mony S, Alicea-Torres K et al (2016) Lectin-type oxidized LDL receptor-1 distinguishes population of human polymorphonuclear myeloid-derived suppressor cells in cancer patients. Sci Immunol 1(2):aaf8943

    Article  PubMed  PubMed Central  Google Scholar 

  • Consonni FM, Porta C, Marino A, Pandolfo C, Mola S, Bleve A et al (2019) Myeloid-derived suppressor cells: ductile targets in disease. Front Immunol 10:949

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cripps JG, Gorham JD (2011) MDSC in autoimmunity. Int Immunopharmacol 11(7):789–793

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dong G, You M, Fan H, Ji J, Ding L, Li P et al (2015) 17β-estradiol contributes to the accumulation of myeloid-derived suppressor cells in blood by promoting TNF-α secretion. Acta Biochim Biophys Sin (shanghai) 47(8):620–629

    Article  CAS  Google Scholar 

  • Elliott LA, Doherty GA, Sheahan K, Ryan EJ (2017) Human tumor-infiltrating myeloid cells: phenotypic and functional diversity. Front Immunol. https://doi.org/10.3389/fimmu.2017.00086

    Article  PubMed  PubMed Central  Google Scholar 

  • Fujii W, Ashihara E, Hirai H, Nagahara H, Kajitani N, Fujioka K et al (2013) Myeloid-derived suppressor cells play crucial roles in the regulation of mouse collagen-induced arthritis. J Immunol 191(3):1073–1081

    Article  CAS  PubMed  Google Scholar 

  • Gabrilovich DI (2017) Myeloid-derived suppressor cells. Cancer Immunol Res 5(1):3–8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gao X, Liu H, Ding G, Wang Z, Fu H, Ni Z et al (2011) Complement C3 deficiency prevent against the onset of streptozotocin-induced autoimmune diabetes involving expansion of regulatory T cells. Clin Immunol 140(3):236–243

    Article  CAS  PubMed  Google Scholar 

  • Groth C, Hu X, Weber R, Fleming V, Altevogt P, Utikal J et al (2019) Immunosuppression mediated by myeloid-derived suppressor cells (MDSCs) during tumour progression. Br J Cancer 120(1):16–25

    Article  CAS  PubMed  Google Scholar 

  • Guan Q, Moreno S, Qing G, Weiss CR, Lu L, Bernstein CN et al (2013) The role and potential therapeutic application of myeloid-derived suppressor cells in TNBS-induced colitis. J Leukoc Biol 94(4):803–811

    Article  CAS  PubMed  Google Scholar 

  • Guo C, Hu F, Yi H, Feng Z, Li C, Shi L et al (2016) Myeloid-derived suppressor cells have a proinflammatory role in the pathogenesis of autoimmune arthritis. Ann Rheum Dis 75(1):278–285

    Article  CAS  PubMed  Google Scholar 

  • Haile LA, von Wasielewski R, Gamrekelashvili J, Krüger C, Bachmann O, Westendorf AM et al (2008) Myeloid-derived suppressor cells in inflammatory bowel disease: a new immunoregulatory pathway. Gastroenterology 135(3):871–881

    Article  CAS  PubMed  Google Scholar 

  • Ioannou M, Alissafi T, Lazaridis I, Deraos G, Matsoukas J, Gravanis A et al (2012) Crucial role of granulocytic myeloid-derived suppressor cells in the regulation of central nervous system autoimmune disease. J Immunol 188(3):1136–1146

    Article  CAS  PubMed  Google Scholar 

  • Iranshahi N, Assar S, Amiri SM, Zafari P, Fekri A, Taghadosi M (2019) Decreased gene expression of Epstein-Barr virus-induced gene 3 (EBI-3) may contribute to the pathogenesis of rheumatoid arthritis. Immunol Invest 48(4):367–377

    Article  CAS  PubMed  Google Scholar 

  • Ji J, Xu J, Zhao S, Liu F, Qi J, Song Y et al (2016) Myeloid-derived suppressor cells contribute to systemic lupus erythaematosus by regulating differentiation of Th17 cells and tregs. Clin Sci (lond) 130(16):1453–1467

    Article  CAS  Google Scholar 

  • Jiao Z, Hua S, Wang W, Wang H, Gao J, Wang X (2013) Increased circulating myeloid-derived suppressor cells correlated negatively with Th17 cells in patients with rheumatoid arthritis. Scand J Rheumatol 42(2):85–90

    Article  CAS  PubMed  Google Scholar 

  • Kim N-R, Kim Y-J (2019) Oxaliplatin regulates myeloid-derived suppressor cell-mediated immunosuppression via downregulation of nuclear factor-κB signaling. Cancer Med 8(1):276–288

    Article  CAS  PubMed  Google Scholar 

  • King IL, Dickendesher TL, Segal BM (2009) Circulating Ly-6C+ myeloid precursors migrate to the CNS and play a pathogenic role during autoimmune demyelinating disease. Blood 113(14):3190–3197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kurkó J, Vida A, Ocskó T, Tryniszewska B, Rauch TA, Glant TT et al (2014) Suppression of proteoglycan-induced autoimmune arthritis by myeloid-derived suppressor cells generated in vitro from murine bone marrow. PLoS ONE 9(11):e111815

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lassmann H (2018) Multiple sclerosis pathology. Cold Spring Harb Perspect Med 8(3):a028936

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Law AMK, Valdes-Mora F, Gallego-Ortega D (2020) Myeloid-derived suppressor cells as a therapeutic target for cancer. Cells 9(3):561

    Article  CAS  PubMed Central  Google Scholar 

  • Le HK, Graham L, Cha E, Morales JK, Manjili MH, Bear HD (2009) Gemcitabine directly inhibits myeloid derived suppressor cells in BALB/c mice bearing 4T1 mammary carcinoma and augments expansion of T cells from tumor-bearing mice. Int Immunopharmacol 9(7–8):900–909

    Article  CAS  PubMed  Google Scholar 

  • Lee C-R, Kwak Y, Yang T, Han JH, Park S-H, Ye MB et al (2016) Myeloid-derived suppressor cells are controlled by regulatory T cells via TGF-β during murine colitis. Cell Rep 17(12):3219–3232

    Article  CAS  PubMed  Google Scholar 

  • Lee SH, Kwon JE, Cho M-L (2018) Immunological pathogenesis of inflammatory bowel disease. Intest Res 16(1):26–42

    Article  PubMed  PubMed Central  Google Scholar 

  • Leukes V, Walzl G, du Plessis N (2020) Myeloid-derived suppressor cells as target of phosphodiesterase-5 inhibitors in host-directed therapeutics for tuberculosis. Front Immunol 11:451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li M, Zhu D, Wang T, Xia X, Tian J, Wang S (2018) Roles of myeloid-derived suppressor cell subpopulations in autoimmune arthritis. Front Immunol. https://doi.org/10.3389/fimmu.2018.02849

    Article  PubMed  PubMed Central  Google Scholar 

  • Lourenço EV, Wong M, Hahn BH, Palma-Diaz MF, Skaggs BJ (2014) Laquinimod delays and suppresses nephritis in lupus-prone mice and affects both myeloid and lymphoid immune cells. Arthritis Rheumatol 66(3):674–685

    Article  PubMed  CAS  Google Scholar 

  • Ma Z, Zhen Y, Hu C, Yi H (2020) Myeloid-derived suppressor cell-derived Arginase-1 oppositely modulates IL-17A and IL-17F through the ESR/STAT3 pathway during colitis in mice. Front Immunol. https://doi.org/10.3389/fimmu.2020.00687

    Article  PubMed  PubMed Central  Google Scholar 

  • Melani C, Sangaletti S, Barazzetta FM, Werb Z, Colombo MP (2007) Amino-biphosphonate-mediated MMP-9 inhibition breaks the tumor-bone marrow axis responsible for myeloid-derived suppressor cell expansion and macrophage infiltration in tumor stroma. Cancer Res 67(23):11438–11446

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moline-Velazquez V, Cuervo H, Vila-Del SV, Ortega MC, Clemente D, de Castro F (2011) Myeloid-derived suppressor cells limit the inflammation by promoting T lymphocyte apoptosis in the spinal cord of a murine model of multiple sclerosis. Brain Pathol 21:678–691

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moschen AR, Tilg H, Raine T (2019) IL-12, IL-23 and IL-17 in IBD: immunobiology and therapeutic targeting. Nat Rev Gastroenterol Hepatol 16(3):185–196

    Article  CAS  PubMed  Google Scholar 

  • Naiditch H, Shurin MR, Shurin GV (2011) Targeting myeloid regulatory cells in cancer by chemotherapeutic agents. Immunol Res 50(2–3):276–285

    Article  CAS  PubMed  Google Scholar 

  • Narkeviciute I, Mieliauskaite D, Mackiewicz Z, Butrimiene I, Viliene R, Dumalakiene I (2018) Distribution of myeloid-derived suppressor cells in rheumatoid arthritis and sjögren’s syndrome. Arch Rheumatol 34(1):53–61

    Article  PubMed Central  Google Scholar 

  • Nishimura K, Saegusa J, Matsuki F, Akashi K, Kageyama G, Morinobu A (2015) Tofacitinib facilitates the expansion of myeloid-derived suppressor cells and ameliorates arthritis in SKG mice. Arthritis Rheumatol 67(4):893–902

    Article  CAS  PubMed  Google Scholar 

  • Ostrand-Rosenberg S, Fenselau C (2018) Myeloid-derived suppressor cells: immune-suppressive cells that impair antitumor immunity and are sculpted by their environment. J Immunol 200(2):422–431 (Baltimore, Md: 1950)

    Article  CAS  PubMed  Google Scholar 

  • Park MJ, Lee SH, Kim EK, Lee EJ, Park SH, Kwok SK et al (2016) Myeloid-derived suppressor cells induce the expansion of regulatory B cells and ameliorate autoimmunity in the sanroque mouse model of systemic lupus erythematosus. Arthritis Rheumatol 68(11):2717–2727

    Article  CAS  PubMed  Google Scholar 

  • Qi J, Tang X, Li W, Chen W, Yao G, Sun L (2020) Mesenchymal stem cells inhibited the differentiation of MDSCs via COX2/PGE2 in experimental sialadenitis. Stem Cell Res Ther 11(1):325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Radmanesh F, Mahmoudi M, Yazdanpanah E, Keyvani V, Kia N, Nikpoor AR et al (2020) The immunomodulatory effects of mesenchymal stromal cell-based therapy in human and animal models of systemic lupus erythematosus. IUBMB Life 72(11):2366–2381

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez-Calvo T, Ekwall O, Amirian N, Zapardiel-Gonzalo J, von Herrath MG (2014) Increased immune cell infiltration of the exocrine pancreas: a possible contribution to the pathogenesis of type 1 diabetes. Diabetes 63(11):3880–3890

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Samimi Z, Kardideh B, Zafari P, Bahrehmand F, Roghani SA, Taghadosi M (2019) The impaired gene expression of adenosine monophosphate-activated kinase (AMPK), a key metabolic enzyme in leukocytes of newly diagnosed rheumatoid arthritis patients. Mol Biol Rep 46(6):6353–6360

    Article  CAS  PubMed  Google Scholar 

  • Sander LE, Sackett SD, Dierssen U, Beraza N, Linke RP, Müller M et al (2010) Hepatic acute-phase proteins control innate immune responses during infection by promoting myeloid-derived suppressor cell function. J Exp Med 207(7):1453–1464

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Suzuki E, Kapoor V, Jassar AS, Kaiser LR, Albelda SM (2005) Gemcitabine selectively eliminates splenic Gr-1+/CD11b+ myeloid suppressor cells in tumor-bearing animals and enhances antitumor immune activity. Clin Cancer Res 11(18):6713–6721

    Article  CAS  PubMed  Google Scholar 

  • Theofilopoulos AN, Kono DH, Baccala R (2017) The multiple pathways to autoimmunity. Nat Immunol 18(7):716–724

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Trigunaite A, Khan A, Der E, Song A, Varikuti S, J⊘rgensen TN (2013) Gr-1highCD11b+ cells suppress b cell differentiation and lupus-like disease in lupus-prone male mice. Arthritis Rheum 65(9):2392–2402

    Article  CAS  PubMed  Google Scholar 

  • Tseng C-W, Hung C-F, Alvarez RD, Trimble C, Huh WK, Kim D et al (2008) Pretreatment with cisplatin enhances E7-specific CD8+ T-Cell-mediated antitumor immunity induced by DNA vaccination. Clin Cancer Res off J Am Assoc Cancer Res 14(10):3185–3192

    Article  CAS  Google Scholar 

  • Tu J, Hong W, Zhang P, Wang X, Körner H, Wei W (2018) Ontology and function of fibroblast-like and macrophage-like synoviocytes: how do they talk to each other and can they be targeted for rheumatoid arthritis therapy? Front Immunol 9:1467

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tumino N, Di Pace AL, Besi F, Quatrini L, Vacca P, Moretta L (2021) Interaction between MDSC and NK cells in solid and hematological malignancies: impact on HSCT. Front Immunol. https://doi.org/10.3389/fimmu.2021.638841

    Article  PubMed  PubMed Central  Google Scholar 

  • Veglia F, Perego M, Gabrilovich D (2018) Myeloid-derived suppressor cells coming of age. Nat Immunol 19(2):108–119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Veglia F, Sanseviero E, Gabrilovich DI (2021) Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity. Nat Rev Immunol. https://doi.org/10.1038/s41577-020-00490-y

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang W, Jiao Z, Duan T, Liu M, Zhu B, Zhang Y et al (2015) Functional characterization of myeloid-derived suppressor cell subpopulations during the development of experimental arthritis. Eur J Immunol 45(2):464–473

    Article  CAS  PubMed  Google Scholar 

  • Wesolowski R, Markowitz J, Carson WE (2013) Myeloid derived suppressor cells – a new therapeutic target in the treatment of cancer. J Immunother Cancer 1(1):10

    Article  PubMed  PubMed Central  Google Scholar 

  • Wu H, Zhen Y, Ma Z, Li H, Yu J, Xu Z-G et al (2016) Arginase-1–dependent promotion of TH17 differentiation and disease progression by MDSCs in systemic lupus erythematosus. Sci Transl Med 8(331):331ra40

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yan L, Liang M, Yang T, Ji J, Jose Kumar Sreena GS, Hou X et al (2020) The immunoregulatory role of myeloid-derived suppressor cells in the pathogenesis of rheumatoid arthritis. Front Immunol 11:568362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yi H, Guo C, Yu X, Zuo D, Wang XY (2012) Mouse CD11b+Gr-1+ myeloid cells can promote Th17 cell differentiation and experimental autoimmune encephalomyelitis. J Immunol 189(9):4295–4304

    Article  CAS  PubMed  Google Scholar 

  • Yin B, Ma G, Yen C-Y, Zhou Z, Wang GX, Divino CM et al (2010) Myeloid-derived suppressor cells prevent type 1 diabetes in murine models. J Immunol 185(10):5828–5834 (Baltimore, Md: 1950)

    Article  CAS  PubMed  Google Scholar 

  • Zafari P, Yari K, Mostafaei S, Iranshahi N, Assar S, Fekri A et al (2018) Analysis of helios gene expression and Foxp3 TSDR methylation in the newly diagnosed rheumatoid arthritis patients. Immunol Invest 47(6):632–642

    Article  CAS  PubMed  Google Scholar 

  • Zafari P, Zarifian A, Alizadeh-Navaei R, Taghadosi M, Rafiei A, Samimi Z et al (2020) Asymmetric and symmetric dimethylarginine concentration as an indicator of cardiovascular diseases in rheumatoid arthritis patients: a systematic review and meta-analysis of case-control studies. Clin Rheumatol 39(1):127–134

    Article  PubMed  Google Scholar 

  • Zhang J, Wang B, Zhang W, Wei Y, Bian Z, Zhang C-Y et al (2013) Protein tyrosine phosphatase 1B deficiency ameliorates murine experimental colitis via the expansion of myeloid-derived suppressor cells. PLoS ONE 8(8):e70828

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Author information

Authors and Affiliations

  1. Doctor of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Ehsan Nourbakhsh

  2. Bachelor of Cell Biology and Molecular-Genetics, Marand Azad University, Marand, Iran

    Ali Mohammadi

  3. Department of Electrical Engineering, University of Tehran, Tehran, Iran

    Mohammad Salemizadeh Parizi

  4. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran

    Atena Mansouri

  5. Internist, Assistant Professor, Department of Internal Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Farnoosh Ebrahimzadeh

Authors
  1. Ehsan Nourbakhsh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ali Mohammadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mohammad Salemizadeh Parizi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Atena Mansouri
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Farnoosh Ebrahimzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

EN and FE contributed to the idea design and literature search. AM and MS wrote parts of the manuscript. EN contributed to designing the figures. AMn contributed to language editing and revision.

Corresponding author

Correspondence to Farnoosh Ebrahimzadeh.

Ethics declarations

Conflict of interest

None.

Ethical approval

It is not applicable.

Informed consent

It is not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nourbakhsh, E., Mohammadi, A., Salemizadeh Parizi, M. et al. Role of Myeloid-derived suppressor cell (MDSC) in autoimmunity and its potential as a therapeutic target. Inflammopharmacol 29, 1307–1315 (2021). https://doi.org/10.1007/s10787-021-00846-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10787-021-00846-3

Keywords

Search

Navigation