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Dendritic cells transduced to express interleukin 4 reduce diabetes onset in both normoglycemic and prediabetic nonobese diabetic mice

Ruffner, MA and Robbins, PD (2010) Dendritic cells transduced to express interleukin 4 reduce diabetes onset in both normoglycemic and prediabetic nonobese diabetic mice. PLoS ONE, 5 (7).

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Abstract

Background: We and others have previously demonstrated that treatment with bone marrow derived DC genetically modified to express IL-4 reduce disease pathology in mouse models of collagen-induced arthritis and delayed-type hypersensitivity. Moreover, treatment of normoglycemic NOD mice with bone marrow derived DC, genetically modified to express interleukin 4 (IL-4), reduces the onset of hyperglycemia in a significant number of animals. However, the mechanism(s) through which DC expressing IL-4 function to prevent autoimmune diabetes and whether this treatment can reverse disease in pre-diabetic NOD mice are unknown. Methodology/Principal Findings: DC were generated from the bone marrow of NOD mice and transduced with adenoviral vectors encoding soluble murine IL-4 (DC/sIL-4), a membrane-bound IL-4 construct, or empty vector control. Female NOD mice were segregated into normoglycemic (<150mg/dL) and prediabetic groups (between 150 and 250 mg/dL) on the basis of blood glucose measurements, and randomized for adoptive transfer of 106 DC via a single i.v. injection. A single injection of DC/sIL-4, when administered to normoglycemic 12-week old NOD mice, significantly reduced the number of mice that developed diabetes. Furthermore, DC/sIL-4, but not control DC, decreased the number of mice progressing to diabetes when given to prediabetic NOD mice 12-16 weeks of age. DC/sIL-4 treatment also significantly reduced islet mononuclear infiltration and increased the expression of FoxP3 in the pancreatic lymph nodes of a subset of treated animals. Furthermore, DC/sIL-4 treatment altered the antigen-specific Th2:Th1 cytokine profiles as determined by ELISPOT of splenocytes in treated animals. Conclusions: Adoptive transfer of DC transduced to express IL-4 into both normoglycemic and prediabetic NOD mice is an effective treatment for T1D. © 2010 Ruffner, Robbins.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Ruffner, MA
Robbins, PDprobb@pitt.eduPROBB
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorMaedler, KathrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 20 August 2010
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 5
Number: 7
DOI or Unique Handle: 10.1371/journal.pone.0011848
Schools and Programs: Swanson School of Engineering > Bioengineering
Refereed: Yes
MeSH Headings: Adenoviridae; Animals; Cells, Cultured; Dendritic Cells--metabolism; Diabetes Mellitus--genetics; Diabetes Mellitus--therapy; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Forkhead Transcription Factors--genetics; Forkhead Transcription Factors--metabolism; Glucose Tolerance Test; Hyperglycemia--genetics; Hyperglycemia--therapy; Interleukin-4--genetics; Interleukin-4--metabolism; Mice; Mice, Inbred NOD; Polymerase Chain Reaction; Prediabetic State--genetics; Prediabetic State--therapy
Other ID: NLM PMC2912295
PubMed Central ID: PMC2912295
PubMed ID: 20686610
Date Deposited: 15 Aug 2012 18:18
Last Modified: 26 Jan 2019 17:55
URI: http://d-scholarship.pitt.edu/id/eprint/13391

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