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Published in: Immunologic Research 1/2015

01-05-2015

Immune protective effect of human alpha-1-antitrypsin gene during β cell transplantation in diabetic mice

Authors: Lu Yang, Yu-Ting Liao, Xiao-Fei Yang, Li-Wei Reng, Hui Qi, Fu-Rong Li

Published in: Immunologic Research | Issue 1/2015

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Abstract

Type 1 diabetes (T1D) is a chronic autoimmune disease in which β cells are destroyed. Islet transplantation is the most promising therapeutic treatment for T1D patients. However, allograft rejection and autoimmune reaction have been recognized as primary causes of graft loss after transplantation. Alpha-1-antitrypsin (AAT) is an important serine protease inhibitor in serum. AAT is characterized by anti-inflammation, anti-apoptosis, and induction-specific immunological tolerance. In this study, we successfully established NIT-hAAT cell lines, which are murine islet β cell lines with stable expression of human AAT (hAAT) gene. These NIT-hAAT cells were transplanted under the left kidney capsule of BALB/c diabetic mice. Interestingly, the sustained expression of hAAT in vivo can block the inflammatory cell infiltration and reduce the production of proinflammatory cytokines to effectively prevent nonspecific inflammation. Results showed that hAAT can inhibit the proliferation of lymphocytes, shift the balance between Th17 and Treg, and suppress the maturation of dendritic cells. Therefore, hAAT can serve as a beneficial immunomodulator that limits immune rejection to prolong islet allograft survival and achieve long-term successful transplant outcomes.
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Metadata
Title
Immune protective effect of human alpha-1-antitrypsin gene during β cell transplantation in diabetic mice
Authors
Lu Yang
Yu-Ting Liao
Xiao-Fei Yang
Li-Wei Reng
Hui Qi
Fu-Rong Li
Publication date
01-05-2015
Publisher
Springer US
Published in
Immunologic Research / Issue 1/2015
Print ISSN: 0257-277X
Electronic ISSN: 1559-0755
DOI
https://doi.org/10.1007/s12026-015-8636-2

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