Cytokine-Induced Myeloid-Derived Suppressor Cells Demonstrate Their Immunoregulatory Functions to Prolong the Survival of Diabetic Mice

Type 1 diabetes is an inflammatory state. Myeloid-derived suppressive cells (MDSCs) originate from immature myeloid cells and quickly expand to control host immunity during infection, inflammation, trauma, and cancer. This study presents an ex vivo procedure to develop MDSCs from bone marrow cells p...

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Main Authors: Tung-Teng Li, Chun-Liang Lin, Meihua Chiang, Jie-Teng He, Chien-Hui Hung, Ching-Chuan Hsieh
Format: Article
Language:English
Published: MDPI AG 2023-05-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/12/11/1507
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author Tung-Teng Li
Chun-Liang Lin
Meihua Chiang
Jie-Teng He
Chien-Hui Hung
Ching-Chuan Hsieh
author_facet Tung-Teng Li
Chun-Liang Lin
Meihua Chiang
Jie-Teng He
Chien-Hui Hung
Ching-Chuan Hsieh
author_sort Tung-Teng Li
collection DOAJ
description Type 1 diabetes is an inflammatory state. Myeloid-derived suppressive cells (MDSCs) originate from immature myeloid cells and quickly expand to control host immunity during infection, inflammation, trauma, and cancer. This study presents an ex vivo procedure to develop MDSCs from bone marrow cells propagated from granulocyte–macrophage-colony-stimulating factor (GM-CSF), interleukin (IL)-6, and IL-1β cytokines expressing immature morphology and high immunosuppression of T-cell proliferation. The adoptive transfer of cytokine-induced MDSCs (cMDSCs) improved the hyperglycemic state and prolonged the diabetes-free survival of nonobese diabetic (NOD) mice with severe combined immune deficiency (SCID) induced by reactive splenic T cells harvested from NOD mice. In addition, the application of cMDSCs reduced fibronectin production in the renal glomeruli and improved renal function and proteinuria in diabetic mice. Moreover, cMDSCs use mitigated pancreatic insulitis to restore insulin production and reduce the levels of HbA1c. In conclusion, administering cMDSCs propagated from GM-CSF, IL-6, and IL-1β cytokines provides an alternative immunotherapy protocol for treating diabetic pancreatic insulitis and renal nephropathy.
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spelling doaj.art-bb930815615e42c5b5fd43787e099fa72023-11-18T07:41:01ZengMDPI AGCells2073-44092023-05-011211150710.3390/cells12111507Cytokine-Induced Myeloid-Derived Suppressor Cells Demonstrate Their Immunoregulatory Functions to Prolong the Survival of Diabetic MiceTung-Teng Li0Chun-Liang Lin1Meihua Chiang2Jie-Teng He3Chien-Hui Hung4Ching-Chuan Hsieh5Division of General Surgery, Chang-Gung Memorial Hospital, Chiayi 61302, TaiwanDepartment of Nephrology, Chang-Gung Memorial Hospital, Chiayi 61302, TaiwanDivision of General Surgery, Chang-Gung Memorial Hospital, Chiayi 61302, TaiwanDivision of General Surgery, Chang-Gung Memorial Hospital, Chiayi 61302, TaiwanCollege of Medicine, Chang-Gung University, Taoyuan 33302, TaiwanDivision of General Surgery, Chang-Gung Memorial Hospital, Chiayi 61302, TaiwanType 1 diabetes is an inflammatory state. Myeloid-derived suppressive cells (MDSCs) originate from immature myeloid cells and quickly expand to control host immunity during infection, inflammation, trauma, and cancer. This study presents an ex vivo procedure to develop MDSCs from bone marrow cells propagated from granulocyte–macrophage-colony-stimulating factor (GM-CSF), interleukin (IL)-6, and IL-1β cytokines expressing immature morphology and high immunosuppression of T-cell proliferation. The adoptive transfer of cytokine-induced MDSCs (cMDSCs) improved the hyperglycemic state and prolonged the diabetes-free survival of nonobese diabetic (NOD) mice with severe combined immune deficiency (SCID) induced by reactive splenic T cells harvested from NOD mice. In addition, the application of cMDSCs reduced fibronectin production in the renal glomeruli and improved renal function and proteinuria in diabetic mice. Moreover, cMDSCs use mitigated pancreatic insulitis to restore insulin production and reduce the levels of HbA1c. In conclusion, administering cMDSCs propagated from GM-CSF, IL-6, and IL-1β cytokines provides an alternative immunotherapy protocol for treating diabetic pancreatic insulitis and renal nephropathy.https://www.mdpi.com/2073-4409/12/11/1507cytokinemyeloid-derived suppressor cellsdiabetic nephropathypancreatic insulitisimmunotherapy
spellingShingle Tung-Teng Li
Chun-Liang Lin
Meihua Chiang
Jie-Teng He
Chien-Hui Hung
Ching-Chuan Hsieh
Cytokine-Induced Myeloid-Derived Suppressor Cells Demonstrate Their Immunoregulatory Functions to Prolong the Survival of Diabetic Mice
Cells
cytokine
myeloid-derived suppressor cells
diabetic nephropathy
pancreatic insulitis
immunotherapy
title Cytokine-Induced Myeloid-Derived Suppressor Cells Demonstrate Their Immunoregulatory Functions to Prolong the Survival of Diabetic Mice
title_full Cytokine-Induced Myeloid-Derived Suppressor Cells Demonstrate Their Immunoregulatory Functions to Prolong the Survival of Diabetic Mice
title_fullStr Cytokine-Induced Myeloid-Derived Suppressor Cells Demonstrate Their Immunoregulatory Functions to Prolong the Survival of Diabetic Mice
title_full_unstemmed Cytokine-Induced Myeloid-Derived Suppressor Cells Demonstrate Their Immunoregulatory Functions to Prolong the Survival of Diabetic Mice
title_short Cytokine-Induced Myeloid-Derived Suppressor Cells Demonstrate Their Immunoregulatory Functions to Prolong the Survival of Diabetic Mice
title_sort cytokine induced myeloid derived suppressor cells demonstrate their immunoregulatory functions to prolong the survival of diabetic mice
topic cytokine
myeloid-derived suppressor cells
diabetic nephropathy
pancreatic insulitis
immunotherapy
url https://www.mdpi.com/2073-4409/12/11/1507
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