Targeting Stem Cell-Derived Tissue-Associated Regulatory T Cells for Type 1 Diabetes Immunotherapy
Purpose of Review
Type 1 diabetes (T1D) is an autoimmune disease in which the immune cells selectively destroy the pancreatic beta (β) cells and results in the deficiency of insulin production. The optimal treatment strategy for T1D should be preventing of β-cell destruction in the pancreas. The purpose of this review is to discuss the immunological therapeutic mechanisms that will help to understand the development and control of β-cell destruction. The review also presents a novel method for development of autoantigen (Ag)-specific regulatory T cells (Tregs) for T1D immunotherapy.
Pancreatic-resident Tregs have the ability to dramatically suppress hyperactive immune cells. Islet cell transplantation is another attractive approach to replace the failed β cells. Due to the limited source of islet cells, research is going on in the use of animal cells and adult stem cells that may be derived from the patient’s own body to produce β cells for transplantation.
The mechanism behind the pancreatic β-cell destruction is largely unknown. In this review, a novel approach for the generation of tissue-associated Tregs from stem cells is considered. The stem cell-derived tissue-associated Tregs have the ability to home to the damaged pancreas to prevent the destruction. The review also provides new insights on the mechanism on how these suppressive immune cells protect the pancreas from the destruction of autoimmune cells. A novel method to develop functional auto Ag-specific Tregs that are derived from induced pluripotent stem cells (iPSCs), i.e., iPSC-Tregs, is discussed. Adoptive transfer of the iPSC-Tregs can substantially suppress T1D development in a murine model.
KeywordsPluripotent stem cells Autoimmune diabetes Regulatory T cells Adoptive transfer Mice
J.S. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
This work was supported by the National Institutes of Health grants R01AI121180, R01CA221867, and R21AI109239 and by the American Diabetes Association (1-16-IBS-281) to J.S.
Compliance with Ethical Standards
Conflict of Interest
Mohammad Haque, Jugal Kishore Das, Xiaofang Xiong, and Jianxun Song declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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