Human Cord Blood Stem Cell-Modulated Regulatory T Lymphocytes Reverse the Autoimmune-Caused Type 1 Diabetes in Nonobese Diabetic (NOD) Mice |
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| Authors: | Yong Zhao Brian Lin Robert Darflinger Yongkang Zhang Mark J Holterman Randal A Skidgel |
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| Institution: | 1. Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America.; 2. Department of Pharmacology, University of Illinois at Chicago, Chicago, Illinois, United States of America.; 3. Department of Surgery, University of Illinois at Chicago, Chicago, Illinois, United States of America.;New York University School of Medicine, United States of America |
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| Abstract: | BackgroundThe deficit of pancreatic islet β cells caused by autoimmune destruction is a crucial issue in type 1 diabetes (T1D). It is essential to fundamentally control the autoimmunity for treatment of T1D. Regulatory T cells (Tregs) play a pivotal role in maintaining self-tolerance through their inhibitory impact on autoreactive effector T cells. An abnormality of Tregs is associated with initiation of progression of T1D.Methodology/Principal FindingsHere, we report that treatment of established autoimmune-caused diabetes in NOD mice with purified autologous CD4+CD62L+ Tregs co-cultured with human cord blood stem cells (CB-SC) can eliminate hyperglycemia, promote islet β-cell regeneration to increase β-cell mass and insulin production, and reconstitute islet architecture. Correspondingly, treatment with CB-SC-modulated CD4+CD62L+ Tregs (mCD4CD62L Tregs) resulted in a marked reduction of insulitis, restored Th1/Th2 cytokine balance in blood, and induced apoptosis of infiltrated leukocytes in pancreatic islets.Conclusions/SignificanceThese data demonstrate that treatment with mCD4CD62L Tregs can reverse overt diabetes, providing a novel strategy for the treatment of type 1 diabetes as well as other autoimmune diseases. |
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