Bibliographic Details
| Title: |
Cholinergic stimulation prevents the development of autoimmune diabetes: Evidence for the modulation of Th17 effector cells via an IFNgamma-dependent mechanism |
| Authors: |
Junu George, Ghada Bashir, Mohammed M Qureshi, Yassir A Mohamed, Jamil Roumanos Azzi, Basel K al-Ramadi, Maria J Fernandez-Cabezudo |
| Source: |
Frontiers in Immunology, Vol 7 (2016) |
| Publisher Information: |
Frontiers Media S.A., 2016. |
| Publication Year: |
2016 |
| Collection: |
LCC:Immunologic diseases. Allergy |
| Subject Terms: |
Acetylcholine, Th17, IFNg, type I diabetes, Anti-inflammatory pathway, Inhibition of AChE, Immunologic diseases. Allergy, RC581-607 |
| More Details: |
Type I diabetes (T1D) results from T cell-mediated damage of pancreatic β-cells and loss of insulin production. The cholinergic anti-inflammatory pathway represents a physiological link connecting the central nervous and immune systems via vagus nerve, and functions to control the release of proinflammatory cytokines. Using the multiple-low-dose streptozotocin (MLD-STZ) model to induce experimental autoimmune diabetes, we investigated the potential of regulating the development of hyperglycemia through administration of paraoxon, a highly specific acetylcholinesterase inhibitor (AChEI). We demonstrate that pretreatment with paraoxon prevented hyperglycemia in STZ-treated C57BL/6 mice. This correlated with a reduction in T cell infiltration into pancreatic islets and preservation of the structure and functionality of β-cells. Gene expression analysis of pancreatic tissue revealed that increased peripheral cholinergic activity prevented STZ-mediated loss of insulin production, this being associated with a reduction in IL-1β, IL-6, and IL-17 proinflammatory cytokines. Intracellular cytokine analysis in splenic T cells demonstrated that inhibition of AChE led to a shift in STZ-induced immune response from a predominantly disease-causing IL-17-expressing Th17 cells to IFNγ-positive Th1 cells. Consistent with this conclusion, inhibition of AChE failed to prevent STZ-induced hyperglycemia in IFNγ-deficient mice. Our results provide mechanistic evidence for the prevention of murine T1D by inhibition of AChE and suggest a promising strategy for modulating disease severity. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1664-3224 |
| Relation: |
http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00419/full; https://doaj.org/toc/1664-3224 |
| DOI: |
10.3389/fimmu.2016.00419 |
| Access URL: |
https://doaj.org/article/dd3ed4718ba843c49431a71798eb565b |
| Accession Number: |
edsdoj.3ed4718ba843c49431a71798eb565b |
| Database: |
Directory of Open Access Journals |
