Mohammad Haque1, Jugal Kishore Das1, Xiaofang Xiong1, Jianxun Song2. 1. Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, 1359 TAMU, 8447 Riverside Pkwy, MREB 2, Bryan, TX, 77807-3260, USA. 2. Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, 1359 TAMU, 8447 Riverside Pkwy, MREB 2, Bryan, TX, 77807-3260, USA. jus35@tamu.edu.
Abstract
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. RECENT FINDINGS: 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.
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. RECENT FINDINGS: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.
Authors: René Maehr; Shuibing Chen; Melinda Snitow; Thomas Ludwig; Lisa Yagasaki; Robin Goland; Rudolph L Leibel; Douglas A Melton Journal: Proc Natl Acad Sci U S A Date: 2009-08-31 Impact factor: 11.205
Authors: John Andersson; Dat Q Tran; Marko Pesu; Todd S Davidson; Heather Ramsey; John J O'Shea; Ethan M Shevach Journal: J Exp Med Date: 2008-08-18 Impact factor: 14.307