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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MDPI AG
2023-05-01
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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. |
first_indexed | 2024-03-11T03:09:52Z |
format | Article |
id | doaj.art-bb930815615e42c5b5fd43787e099fa7 |
institution | Directory Open Access Journal |
issn | 2073-4409 |
language | English |
last_indexed | 2024-03-11T03:09:52Z |
publishDate | 2023-05-01 |
publisher | MDPI AG |
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series | Cells |
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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