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).
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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Item Type: |
Article
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Status: |
Published |
Creators/Authors: |
Creators | Email | Pitt Username | ORCID  |
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Ruffner, MA | | | | Robbins, PD | probb@pitt.edu | PROBB | |
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Contributors: |
Contribution | Contributors Name | Email | Pitt Username | ORCID  |
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Editor | Maedler, Kathrin | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
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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: |
12 Jun 2021 16:55 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/13391 |
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