Increased Levels of Type 1 Interferon in a Type 1 Diabetic Mouse Model Induce the Elimination of B Cells from the Periphery by Apoptosis and Increase their Retention in the Spleen

Abstract

Background: The autoimmune disease type 1 diabetes mellitus (T1D) is associated with a defect in the immune response, which increases susceptibility to infection. We recently demonstrated that prolonged elevated levels of type 1 interferon (IFN) induce lymphocyte exhaustion during T1D. Aims: In the present study, we further investigated the effect of blocking the type I IFN receptor signaling pathway on diabetic dyslipidemia, in which an abnormal lipid profile leads to the exhaustion of B cells and alteration of their distribution and functions. Methods: T1D was induced in a mouse model by an intraperitoneal injection of a single dose (60 mg/kg) of streptozotocin (STZ). Three groups of mice were examined: a non-diabetic control group, a diabetic group and a diabetic group treated with an anti-IFN (alpha, beta and omega) receptor 1 (IFNAR1) blocking antibody to block type I IFN signaling. Results: We observed that induction of T1D was accompanied by a marked destruction of β cells and a reduction in the insulin levels in the diabetic group. Diabetic mice exhibited many changes, including alterations in their lipid profiles, expansion of splenic B cells, increased caspase-3, -8 and -9 activity, and apoptosis in peripheral B cells. Blocking type 1 IFN signaling in diabetic mice significantly returned the insulin and lipid profiles to normal levels, subsequently restored the B cell distribution, and rescued the peripheral B cells from apoptosis. Conclusion: Our data suggest the potential role of type I IFN in mediating diabetic dyslipidemia and an exhausted state of B cells during T1D.

Camel Whey Protein Protects B and T Cells from Apoptosis by Suppressing Activating Transcription Factor-3 (ATF-3)-Mediated Oxidative Stress and Enhancing Phosphorylation of AKT and IκB-α in Type I Diabetic Mice

“…Photographs of the sections were taken; the images were digitized using Adobe Photoshop (Adobe Systems, Mountain View, CA). The numbers of anti-CD3 or anti-CD20-stained cells were determined at 20 random locations in the section taken from five animals from each group using a Leica Qwin 500 image analyzer [3]. …”

“…This leads to an increase in pro-inflammatory cytokines and reactive oxygen species (ROS) and a decrease in insulin secretion [2]. Likewise, T1D contributes to a defect in lymphocyte function, especially in B- and T-lymphocytes, which increases susceptibility to infection [3, 4]. Moreover, hyperglycemia increases the oxidative modification of lipids, DNA, and proteins in various tissues, which is involved in the development of diabetic complications [5].…”

Thymoquinone Rescues T Lymphocytes from Gamma Irradiation-Induced Apoptosis and Exhaustion by Modulating Pro-Inflammatory Cytokine Levels and PD-1, Bax, and Bcl-2 Signaling

“…Cell surface antigen expression was determined by single-parameter fluorescence-activated cell sorter (FACS) analysis as previously described [25][26][27] using the following monoclonal antibodies (mAbs): FITC-conjugated anti-CD4, FITC-conjugated anti-CD8, and FITC-conjugated mouse isotype-matched control mAbs, all purchased from BD Biosciences. After incubation in culture for 4 hours, PBMCs were washed 3 times in PBS, washed 2 times with FACS buffer (1% BSA in PBS) and then double stained with FITCconjugated anti-CD4 and FITC-conjugated anti-CD8 or -IgG2a isotype control at 10 µl of antibody/10 6 cells at 4°C for 30 minutes.…”

Protective Effect of 2-Dodecyl-6-Methoxycyclohexa-2, 5-Diene-1, 4-Dione, Isolated from Averrhoa Carambola L., Against Palmitic Acid-Induced Inflammation and Apoptosis in Min6 Cells by Inhibiting the TLR4-MyD88-NF-κB Signaling Pathway

“…Inflammation and apoptosis play crucial roles in the progression of pancreatic β-cell dysfunction [2].…”