title: 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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Our data suggest the potential role of type I IFN in mediating diabetic dyslipidemia and an exhausted state of B cells during T1D.
authors.affiliation: Zoology Department, Faculty of Science, Minufiya University, Shebin El-Kom, Egypt.
authors.forename: Badr Mohamed
authors.initials: BM
authors.lastname: Badr
authors.forename: Nadia Ahmed
authors.initials: NA
authors.lastname: Moustafa
authors.forename: Heba M Saad
authors.initials: HM
authors.lastname: Eldien
authors.forename: Amany O
authors.initials: AO
authors.lastname: Mohamed
authors.forename: Hany M
authors.initials: HM
authors.lastname: Ibrahim
authors.forename: Ibrahim A
authors.initials: IA
authors.lastname: El-Elaimy
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Mahmoud
authors.forename: Gamal
authors.initials: G
authors.lastname: Badr
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism*; D008055:Lipids / Q000097:blood; D051379:Mice; D010179:Pancreas / Q000473:pathology; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology / Q000473:pathology*; D013311:Streptozocin / Q000633:toxicity
chemical_list: D000906:Antibodies; D007328:Insulin; D007370:Interferon Type I; D008055:Lipids; D013311:Streptozocin; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9