CD33+ HLA-DR– Myeloid-Derived Suppressor Cells Are Increased in Frequency in the Peripheral Blood of Type1 Diabetes Patients with Predominance of CD14+ Subset

Authors

  • Mirhane Hassan Clinical and Chemical Pathology Department, National Research Center, Dokki
  • Hala M. Raslan Internal Medicine Department, National Research Center, Dokki
  • Hesham Gamal Eldin Clinical and Chemical Pathology Department, National Research Center, Dokki
  • Eman Mahmoud Clinical and Chemical Pathology Department, National Research Center, Dokki
  • Hanaa Alm-elhuda Abd Elwajed Clinical and Chemical Pathology Department, National Research Center, Dokki

DOI:

https://doi.org/10.3889/oamjms.2018.080

Keywords:

Myeloid-derived suppressor cells, Type 1 Diabetes, Diabetic nephropathy, CD 14 , MDSCs subsets

Abstract

INTRODUCTION: Type 1 Diabetes Mellitus (T1D) is an autoimmune disease that results from the destruction of insulin-producing beta cells of the pancreas by autoreactive T cells. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that can potently suppress T cell responses.

AIM: To detect the presence of MDSCs in T1D and compare their percentage in T1D versus healthy individuals.

METHOD: Thirty T1D patients were included in the study. Diabetic patients with nephropathy (n = 18) and diabetic patients without nephropathy (n = 12). A control group of healthy individuals (n = 30) were also included. CD33+ and HLA-DR– markers were used to identify MDSCs by flow cytometry. CD14 positive and negative MDSCs subsets were also identified.

RESULTS: MDSCs was significantly increased in T1D than the control group and diabetic patient with nephropathy compared to diabetic patients without nephropathy. M-MDSCs (CD14+ CD33+ HLA–DR−) were the most abundant MDSCs subpopulation in all groups, however their percentage decrease in T1D than the control group.

CONCLUSION: MDSCs are increased in the peripheral blood of T1D with a predominance of the CD14+ MDSCs subset. Future studies are needed to test the immune suppression function of MDSCs in T1D.

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References

Ermann J, Fathman CG. Autoimmune diseases: genes, bugs and failed regulation. Nature Immunology. 2001; 2(9):759-761.

Yang WC. Myeloid-derived Suppressor Cells in Autoimmune Diabetes: Their Anti-diabetic Potential and Mechanism. J Diabetes Metab S. 2013; 12:2. https://doi.org/10.4172/2155-6156.S12-004

Atkinson MA, Eisenbarth GS, Michels AW. Type 1 diabetes. Lancet. 2014; 383(9911):69–82. https://doi.org/10.1016/S0140-6736(13)60591-7

Pasquali L, Giannoukakis N, Trucco M. Induction of immune tolerance to facilitate β cell regeneration in type 1 diabetes. Advanced drug delivery reviews. 2008; 60(2):106-13. https://doi.org/10.1016/j.addr.2007.08.032 PMid:18053613

Hu C, Du W, Zhang X, Wong FS, Wen L. The role of Gr1+ cells after anti-CD20 treatment in type 1 diabetes in nonobese diabetic mice. The Journal of Immunology. 2012; 188(1):294-301. https://doi.org/10.4049/jimmunol.1101590 PMid:22140261 PMCid:PMC4361178

Ribechini E, Greifenberg V, Sandwick S, Lutz MB. Subsets, expansion and activation of myeloid-derived suppressor cells. Medical microbiology and immunology. 2010; 199(3):273-81. https://doi.org/10.1007/s00430-010-0151-4 PMid:20376485

Richardson SJ, Willcox A, Bone AJ, Morgan NG, Foulis AK. Immunopathology of the human pancreas in type-I diabetes. Seminars in immunopathology. 2011; 33(1):9-21. https://doi.org/10.1007/s00281-010-0205-0 PMid:20424842

Filipazzi P, Huber V, Rivoltini L. Phenotype, function and clinical implications of myeloid-derived suppressor cells in cancer patients. Cancer Immunology, Immunotherapy. 2012; 61(2):255-63. https://doi.org/10.1007/s00262-011-1161-9 PMid:22120756

Atretkhany KS, Drutskaya MS. Myeloid-derived suppressor cells and proinflammatory cytokines as targets for cancer therapy. Biochemistry (Moscow). 2016; 81(11):1274-83. https://doi.org/10.1134/S0006297916110055 PMid:27914453

Youn JI, Gabrilovich DI. The biology of myeloidâ€derived suppressor cells: the blessing and the curse of morphological and functional heterogeneity. European journal of immunology. 2010; 40(11):2969-75. https://doi.org/10.1002/eji.201040895 PMid:21061430 PMCid:PMC3277452

Youn JI, Nagaraj S, Collazo M, Gabrilovich DI. Subsets of myeloid-derived suppressor cells in tumor-bearing mice. The Journal of Immunology. 2008; 181(8):5791-802. https://doi.org/10.4049/jimmunol.181.8.5791 PMid:18832739 PMCid:PMC2575748

Peranzoni E, Zilio S, Marigo I, Dolcetti L, Zanovello P, Mandruzzato S, Bronte V. Myeloid-derived suppressor cell heterogeneity and subset definition. Current opinion in immunology. 2010; 22(2):238-44. https://doi.org/10.1016/j.coi.2010.01.021 PMid:20171075

Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nature reviews immunology. 2009; 9(3):162. https://doi.org/10.1038/nri2506 PMid:19197294 PMCid:PMC2828349

Talmadge JE, Gabrilovich DI. History of myeloid-derived suppressor cells. Nature Reviews Cancer. 2013; 13(10):739. https://doi.org/10.1038/nrc3581 PMid:24060865 PMCid:PMC4358792

Gielen PR, Schulte BM, Kers-Rebel ED, Verrijp K, Petersen-Baltussen HM, Ter Laan M, Wesseling P, Adema GJ. Increase in both CD14-positive and CD15-positive myeloid-derived suppressor cell subpopulations in the blood of patients with glioma but predominance of CD15-positive myeloid-derived suppressor cells in glioma tissue. Journal of neuropathology & experimental neurology. 2015; 74(5):390-400. https://doi.org/10.1097/NEN.0000000000000183 PMid:25853692

Lindau D, Gielen P, Kroesen M, Wesseling P, Adema GJ. The immunosuppressive tumour network: myeloidâ€derived suppressor cells, regulatory T cells and natural killer T cells. Immunology. 2013; 138(2):105-15. https://doi.org/10.1111/imm.12036 PMid:23216602 PMCid:PMC3575763

Yin B, Ma G, Yen CY, Zhou Z, Wang GX, Divino CM, Casares S, Chen SH, Yang WC, Pan PY. Myeloid-derived suppressor cells prevent type 1 diabetes in murine models. The Journal of Immunology. 2010; 185(10):5828-34. https://doi.org/10.4049/jimmunol.0903636 PMid:20956337 PMCid:PMC4355963

American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes care. 2010; 33(Suppl 1):S62. https://doi.org/10.2337/dc10-S062 PMid:20042775 PMCid:PMC2797383

Nazar CM. Diabetic nephropathy; principles of diagnosis and treatment of diabetic kidney disease. Journal of nephropharmacology. 2014; 3(1):15.

Luan Y, Mosheir E, Menon MC, Wilson D, Woytovich C, Ochando J, Murphy B. Monocytic Myeloidâ€Derived Suppressor Cells Accumulate in Renal Transplant Patients and Mediate CD4+ Foxp3+ Treg Expansion. American journal of transplantation. 2013; 13(12):3123-31. https://doi.org/10.1111/ajt.12461 PMid:24103111

Zhang Q, Fujino M, Xu J, Li XK. The role and potential therapeutic application of myeloid-derived suppressor cells in allo-and autoimmunity. Mediators of inflammation. 2015; Article ID 421927:1-14. https://doi.org/10.1155/2015/421927.

Whitfield-Larry F, Felton J, Buse J, Su MA. Myeloid-derived suppressor cells are increased in frequency but not maximally suppressive in peripheral blood of Type 1 Diabetes Mellitus patients. Clinical Immunology. 2014; 153(1):156-64. https://doi.org/10.1016/j.clim.2014.04.006 PMid:24769355

Kracht MJ, Zaldumbide A, Roep BO. Neoantigens and microenvironment in type 1 diabetes: lessons from antitumor immunity. Trends in Endocrinology & Metabolism. 2016; 27(6):353-62. https://doi.org/10.1016/j.tem.2016.03.013 PMid:27094501

Piemonti L, Leone BE, Nano R, Saccani A, Monti P, Maffi P, Bianchi G, Sica A, Peri G, Melzi R, Aldrighetti L. Human pancreatic islets produce and secrete MCP-1/CCL2: relevance in human islet transplantation. Diabetes. 2002; 51(1):55-65. https://doi.org/10.2337/diabetes.51.1.55 PMid:11756323

Roep BO, Kleijwegt FS, Van Halteren AG, Bonato V, Boggi U, Vendrame F, Marchetti P, Dotta F. Islet inflammation and CXCL10 in recentâ€onset type 1 diabetes. Clinical & Experimental Immunology. 2010; 159(3):338-43. https://doi.org/10.1111/j.1365-2249.2009.04087.x PMid:20059481 PMCid:PMC2819499

Büll C, den Brok MH, Adema GJ. Sweet escape: sialic acids in tumor immune evasion. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer. 2014; 1846(1):238-46. https://doi.org/10.1016/j.bbcan.2014.07.005 PMid:25026312

Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nature medicine. 2013; 19(11):1423. https://doi.org/10.1038/nm.3394 PMid:24202395 PMCid:PMC3954707

Coppieters KT, Dotta F, Amirian N, Campbell PD, Kay TW, Atkinson MA, Roep BO, von Herrath MG. Demonstration of islet-autoreactive CD8 T cells in insulitic lesions from recent onset and long-term type 1 diabetes patients. Journal of Experimental Medicine. 2012: jem-20111187. https://doi.org/10.1084/jem.20111187

Eizirik DL, Colli ML, Ortis F. The role of inflammation in insulitis and β-cell loss in type 1 diabetes. Nature Reviews Endocrinology. 2009; 5(4):219. https://doi.org/10.1038/nrendo.2009.21 PMid:19352320

Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010; 140(6):883-99. https://doi.org/10.1016/j.cell.2010.01.025 PMid:20303878 PMCid:PMC2866629

Motallebnezhad M, Jadidi-Niaragh F, Qamsari E S, et al. The immunobiology of myeloid-derived suppressor cells in cancer. Tumor Biology. 2015; 37(2):1387-1406. https://doi.org/10.1007/s13277-015-4477-9 PMid:26611648

Haile LA, Von Wasielewski R, Gamrekelashvili J, Krüger C, Bachmann O, Westendorf AM, Buer J, Liblau R, Manns MP, Korangy F, Greten TF. Myeloid-derived suppressor cells in inflammatory bowel disease: a new immunoregulatory pathway. Gastroenterology. 2008; 135(3):871-81. https://doi.org/10.1053/j.gastro.2008.06.032 PMid:18674538

Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nature reviews immunology. 2009; 9(3):162. https://doi.org/10.1038/nri2506 PMid:19197294 PMCid:PMC2828349

Lechner MG, Liebertz DJ, Epstein AL. Correction: Characterization of Cytokine-Induced Myeloid-Derived Suppressor Cells from Normal Human Peripheral Blood Mononuclear Cells. The Journal of Immunology. 2010; 185(9):5668-5668. https://doi.org/10.4049/jimmunol.1090100

Maedler K, Sergeev P, Ris F, Oberholzer J, Joller-Jemelka HI, Spinas GA, Kaiser N, Halban PA, Donath MY. Glucose-induced β cell production of IL-1β contributes to glucotoxicity in human pancreatic islets. The Journal of clinical investigation. 2002; 110(6):851-60. https://doi.org/10.1172/JCI200215318 PMid:12235117 PMCid:PMC151125

Campbell IL, Kay TW, Oxbrow L, Harrison LC. Essential role for interferon-gamma and interleukin-6 in autoimmune insulin-dependent diabetes in NOD/Wehi mice. The Journal of clinical investigation. 1991; 87(2):739-42. https://doi.org/10.1172/JCI115055 PMid:1899431 PMCid:PMC296368

Xing YF, Cai RM, Lin Q, Ye QJ, Ren JH, Yin LH, Li X. Expansion of polymorphonuclear myeloid-derived suppressor cells in patients with end-stage renal disease may lead to infectious complications. Kidney international. 2017; 91(5):1236-42. https://doi.org/10.1016/j.kint.2016.12.015 PMid:28215666

Greten TF, Manns MP, Korangy F. Myeloid derived suppressor cells in human diseases. International immunopharmacology. 2011; 11(7):802-7. https://doi.org/10.1016/j.intimp.2011.01.003 PMid:21237299 PMCid:PMC3478130

Ning G, She L, Lu L, Liu Y, Zeng Y, Yan Y, Lin C. Analysis of monocytic and granulocytic myeloid-derived suppressor cells subsets in patients with hepatitis C virus infection and their clinical significance. BioMed research international. 2015; 2015:1-8. https://doi.org/10.1155/2015/385378

Published

2018-02-09

How to Cite

1.
Hassan M, Raslan HM, Eldin HG, Mahmoud E, Abd Elwajed HA- elhuda. CD33+ HLA-DR– Myeloid-Derived Suppressor Cells Are Increased in Frequency in the Peripheral Blood of Type1 Diabetes Patients with Predominance of CD14+ Subset. Open Access Maced J Med Sci [Internet]. 2018 Feb. 9 [cited 2024 Apr. 24];6(2):303-9. Available from: https://oamjms.eu/index.php/mjms/article/view/oamjms.2018.080

Issue

Section

B - Clinical Sciences

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