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Oxidative Medicine and Cellular Longevity
Volume 2013, Article ID 148725, 12 pages
http://dx.doi.org/10.1155/2013/148725
Research Article

Blocking Type I Interferon Signaling Rescues Lymphocytes from Oxidative Stress, Exhaustion, and Apoptosis in a Streptozotocin-Induced Mouse Model of Type I Diabetes

1Zoology Department, Faculty of Science, Minufiya University, Shebin El-Kom, Egypt
2Histology Department, Faculty of Medicine, Assiut University, Assiut, Egypt
3Department of Urology/Surgery, College of Medicine, King Saud University, Saudi Arabia
4Princess Al-Johara Al-Ibrahim Center for Cancer Research, College of Medicine, King Saud University, P.O. Box 7805, Riyadh 11472, Saudi Arabia
5Zoology Department, Faculty of Science, Assiut University, Assiut 71516, Egypt

Received 10 November 2012; Revised 10 January 2013; Accepted 28 January 2013

Academic Editor: Felipe Dal-Pizzol

Copyright © 2013 Hany M. Ibrahim et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Elevated levels of type I interferon (IFN) during type 1 diabetes mellitus (T1D) are associated with a defective immune response. In the present study, we investigated whether blocking type I IFN signaling during streptozotocin- (STZ-) induced T1D in mice improves lymphocyte proliferation and escape from continuous apoptosis. Three groups of mice were examined: diabetic mice, type I IFN signaling-incompetent diabetic mice, and control nondiabetic mice. We first found that diabetes induction was accompanied by an elevation in the plasma levels of reactive oxygen species (ROS), hydroperoxide, malondialdehyde (MDN), and the proinflammatory cytokines IL-1α, IL-1β, IL-6, and CXCL10. Blocking type 1 IFN signaling in diabetic mice significantly decreased the levels of oxidative stress and proinflammatory cytokines. In addition, lymphocytes from diabetic mice exhibited a marked reduction in their proliferative capacity, increased apoptosis, upregulation of the exhaustion marker PD-1, and aberrant phosphorylation of STAT1, STAT2, AKT and IκB-α. Interestingly, following the blocking of type I IFN signaling in diabetic mice, the lymphocytes exhibited restored proliferative capacity, decreased apoptosis, normal expression of PD-1, and normal phosphorylation of STAT1, STAT2, AKT and IκB-α. Our data suggest that elevated levels of type I IFN during T1D trigger lymphocyte exhaustion and a defective lymphocyte-medicated immune response.