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

Immunologic Research
Lu YangFu-Rong Li

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...Continue Reading

References

Oct 9, 2002·International Journal of Experimental Diabetes Research·W L Suarez-Pinzon, A Rabinovitch
Aug 12, 2005·Proceedings of the National Academy of Sciences of the United States of America·Eli C LewisCharles A Dinarello
Mar 16, 2007·Diabetes·Bin ZhangSihong Song
Sep 2, 2008·Clinical and Experimental Immunology·Y LuS Song
Oct 15, 2008·Proceedings of the National Academy of Sciences of the United States of America·Eli C LewisCharles A Dinarello
Feb 7, 2009·Journal of Leukocyte Biology·Gregory B PottLeland Shapiro
Apr 13, 2010·Expert Review of Clinical Immunology·Jamil AzziReza Abdi
May 12, 2010·Clinical and Experimental Immunology·F R LiH X Zhou
Apr 28, 2012·Immunologic Research·Hui QiFu-Rong Li
May 19, 2012·PloS One·Maria KoulmandaTerry B Strom
May 29, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Eyal OzeriEli C Lewis
May 29, 2012·Molecular Medicine·Eli C Lewis
Sep 6, 2012·Proceedings of the National Academy of Sciences of the United States of America·Maria KoulmandaTerry B Strom
Aug 15, 2013·Current Diabetes Reports·J R F Abreu, B O Roep
Jan 15, 2014·Transplant International : Official Journal of the European Society for Organ Transplantation·Koji SugimotoShinichi Matsumoto
Jun 3, 2014·International Journal of Endocrinology·Mazhar A KanakBashoo Naziruddin
Jul 16, 2014·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Anthony BruniAm James Shapiro
Aug 27, 2014·Journal of Diabetes Science and Technology·Gabriella Fleixo-LimaEli C Lewis
Oct 16, 2014·World Journal of Diabetes·Ravindranath Aathira, Vandana Jain
Jan 8, 2015·Frontiers in Immunology·Jens GeginatSergio Abrignani

❮ Previous
Next ❯

Citations

Jan 22, 2017·Transplant International : Official Journal of the European Society for Organ Transplantation·Vaihere DelauneChristian Toso
Nov 26, 2015·The British Journal of Dermatology·I BlancoS Janciauskiene

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autoimmune Diabetes & Tolerance

Patients with type I diabetes lack insulin-producing beta cells due to the loss of immunological tolerance and autoimmune disease. Discover the latest research on targeting tolerance to prevent diabetes.

Allogenic & Autologous Therapies

Allogenic therapies are generated in large batches from unrelated donor tissues such as bone marrow. In contrast, autologous therapies are manufactures as a single lot from the patient being treated. Here is the latest research on allogenic and autologous therapies.

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.