Exendin-4 therapy in NOD mice with new-onset diabetes increases regulatory T cell frequency
| Autor: | Matthew Parker, Song Xue, Todd M. Brusko, Kieran M. Mcgrail, Mark A. Atkinson, Martha Campbell-Thompson, Desmond A. Schatz, Clive Wasserfall, Michael J. Haller, Marcus Moore, Sean M. Mcgrail |
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| Rok vydání: | 2009 |
| Předmět: |
Regulatory T cell
Drug Evaluation Preclinical Incretin Nod Biology T-Lymphocytes Regulatory General Biochemistry Genetics and Molecular Biology Diabetes Mellitus Experimental Interferon-gamma Mice Immune system History and Philosophy of Science In vivo Mice Inbred NOD medicine Animals Hypoglycemic Agents Lymphocyte Count NOD mice Tumor Necrosis Factor-alpha Venoms General Neuroscience Interleukin-10 Interleukin 10 medicine.anatomical_structure Diabetes Mellitus Type 1 Immunology Exenatide Interleukin-2 Female Interleukin-4 Beta cell Peptides |
| Zdroj: | Annals of the New York Academy of Sciences. 1150 |
| ISSN: | 1749-6632 |
| Popis: | Recent studies, albeit controversial, have suggested that the incretin exendin-4 (Ex-4) is capable of inducing beta cell proliferation in vivo. Furthermore, this compound has been shown to enhance the ability of other agents (e.g., anti-CD3, antilymphocyte serum) to reverse type 1 diabetes (T1D) in NOD mice. However, the mechanisms underlying this beneficial action for disease reversal remain largely unclear. Herein, we tested the hypothesis that Ex-4 therapy may act as a stimulator of regulatory T cells (Tregs). We evaluated the effect of Ex-4 (Byetta; 0.2 microg/mouse/day for 30 days) treatment on the frequency and function of Tregs and changes in the cytokine profile of NOD mice with recently diagnosed T1D. In comparison to that of saline-treated control NOD mice, the frequency of Tregs was increased in Ex-4-treated mice. Suppression assays demonstrated a trend towards increased Treg suppression after administration of Ex-4, but were limited by small sample size. Lastly, Ex-4 treatment induced production of IL-10, indicating a possible shift towards a more Th2-like phenotype. Taken collectively, these data suggest that in addition to its potential effects on beta cell proliferation, Ex-4 may also act as a regulator of the immune response. |
| Databáze: | OpenAIRE |
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