title: Administration of recombinant human thioredoxin-1 significantly delays and prevents autoimmune diabetes in nonobese diabetic mice through modulation of autoimmunity.
abstract: BACKGROUND
  Thioredoxin as a biological antioxidant plays an important role in regulating the redox system. The administration of recombinant thioredoxin has been demonstrated to be anti-inflammatory. In this study, the effect of recombinant human thioredoxin-1 (rhTrx-1) in preventing type 1 diabetes (T1D) in nonobese diabetic (NOD) mice was evaluated.
  
  
  METHODS
  Eight-week-old NOD mice were treated with intravenous injection of rhTrx-1 (5 µg/mouse/day) for 5 weeks (5 days a week), followed by every other day for additional 5 weeks. Diabetes onset was monitored twice a week. Pancreatic histology and β-cell mass were examined by hematoxylin and eosin (H&E) and insulin immunohistochemistry staining, respectively. Adoptive transfer experiments were executed to assess autoimmune T cells modulated by rhTrx treatment.
  
  
  RESULTS
  The intravenous administration of rhTrx-1 significantly delayed and prevented T1D in NOD mice. The histology data showed that rhTrx-1 treatment markedly reduced insulitic lesions and significantly preserved insulin-producing β cells. Adoptive transfer of spleen cells from rhTrx-1-treated mice into nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice significantly reduced the diabetes onset than transfer of those from phosphate-buffered saline-treated mice. Adoptive co-transfer experiments demonstrated that spleen cells from rhTrx-1-treated mice significantly delayed diabetes induced by the co-transferred diabetogenic spleen cells from the new-onset diabetic mice.
  
  
  CONCLUSIONS
  Antioxidant rhTrx-1 effectively prevents T1D which may be attributed to its activity to modulate autoimmunity.
authors: Department of Pathology, Immunology and Laboratory Medicine, Diabetes Center of Excellence, University of Florida, Gainesville, FL 32610, USA.
authors: Anna V
authors: AV
authors: Chernatynskaya
authors: Benjamin
authors: B
authors: Looney
authors: Hanbo
authors: H
authors: Hu
authors: Xiaoyan
authors: X
authors: Zhu
authors: Chang-Qing
authors: CQ
authors: Xia
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015551:Autoimmunity / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control*; D005260:Female; D006801:Humans; D050417:Insulin-Secreting Cells / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D013154:Spleen / Q000276:immunology / Q000637:transplantation; D013879:Thioredoxins / Q000494:pharmacology*
chemical_list: D013879:Thioredoxins