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Adjuvant Immunotherapy Increases β Cell Regenerative Factor Reg2 in the Pancreas of Diabetic Mice
- Source :
- Paediatrics Publications
- Publication Year :
- 2010
- Publisher :
- The American Association of Immunologists, 2010.
-
Abstract
- Insulin-producing β cells can partially regenerate in adult pancreatic tissues, both in human and animal models of type 1 diabetes (T1D). Previous studies have shown that treatment with mycobacterial adjuvants such as CFA and bacillus Calmette-Guérin prevents induction and recurrence of T1D in NOD mice with partial recovery of β cell mass. In this study, we investigated factors involved in the regeneration of β cells in the pancreas of NOD mice during diabetes development and after treatment with adjuvants. The Regeneration (Reg) gene family is known to be involved in regeneration of various tissues including β cells. Reg2 expression was found to be upregulated in pancreatic islets both during diabetes development and as a result of adjuvant treatment in diabetic NOD mice and in C57BL/6 mice made diabetic by streptozotocin treatment. The upregulation of Reg2 by adjuvant treatment was independent of signaling through MyD88 and IL-6 because it was not altered in MyD88 or IL-6 knockout mice. We also observed upregulation of Reg2 in the pancreas of diabetic mice undergoing β cell regenerative therapy with exendin-4 or with islet neogenesis-associated protein. Reg2 expression following adjuvant treatment correlated with a reduction in insulitis, an increase in insulin secretion, and an increase in the number of small islets in the pancreas of diabetic NOD mice and with improved glucose tolerance tests in streptozotocin-treated diabetic C57BL/6 mice. In conclusion, adjuvant immunotherapy regulates T1D in diabetic mice and induces Reg2-mediated regeneration of β cells. Copyright © 2010 by The American Association of Immunologists, Inc.
- Subjects :
- medicine.medical_specialty
Blotting, Western
Freund's Adjuvant
Immunology
Gene Expression
Pancreatitis-Associated Proteins
Biology
Diabetes Mellitus, Experimental
Mice
Adjuvants, Immunologic
Downregulation and upregulation
Mice, Inbred NOD
Insulin-Secreting Cells
Internal medicine
Diabetes mellitus
medicine
Animals
Regeneration
Immunology and Allergy
Pancreas
NOD mice
Mice, Knockout
Type 1 diabetes
Reverse Transcriptase Polymerase Chain Reaction
Gene Expression Profiling
Pancreatic islets
Proteins
Streptozotocin
medicine.disease
Immunohistochemistry
Up-Regulation
Mice, Inbred C57BL
Diabetes Mellitus, Type 1
Endocrinology
medicine.anatomical_structure
Chemotherapy, Adjuvant
Female
Immunotherapy
Insulitis
medicine.drug
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 185
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....5d86b50b4e4c00ceb09f181c888f1fe4