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E2-2 Dependent Plasmacytoid Dendritic Cells Control Autoimmune Diabetes.

Hansen, Lisbeth LU ; Schmidt-Christensen, Anja LU ; Gupta, Shashank LU ; Fransén Pettersson, Nina LU ; Hannibal, Tine LU ; Reizis, Boris; Santamaria, Pere and Holmberg, Dan LU (2015) In PLoS ONE 10(12).
Abstract
Autoimmune diabetes is a consequence of immune-cell infiltration and destruction of pancreatic β-cells in the islets of Langerhans. We analyzed the cellular composition of the insulitic lesions in the autoimmune-prone non-obese diabetic (NOD) mouse and observed a peak in recruitment of plasmacytoid dendritic cells (pDCs) to NOD islets around 8-9 weeks of age. This peak coincides with increased spontaneous expression of type-1-IFN response genes and CpG1585 induced production of IFN-α from NOD islets. The transcription factor E2-2 is specifically required for the maturation of pDCs, and we show that knocking out E2-2 conditionally in CD11c+ cells leads to a reduced recruitment of pDCs to pancreatic islets and reduced CpG1585 induced... (More)
Autoimmune diabetes is a consequence of immune-cell infiltration and destruction of pancreatic β-cells in the islets of Langerhans. We analyzed the cellular composition of the insulitic lesions in the autoimmune-prone non-obese diabetic (NOD) mouse and observed a peak in recruitment of plasmacytoid dendritic cells (pDCs) to NOD islets around 8-9 weeks of age. This peak coincides with increased spontaneous expression of type-1-IFN response genes and CpG1585 induced production of IFN-α from NOD islets. The transcription factor E2-2 is specifically required for the maturation of pDCs, and we show that knocking out E2-2 conditionally in CD11c+ cells leads to a reduced recruitment of pDCs to pancreatic islets and reduced CpG1585 induced production of IFN-α during insulitis. As a consequence, insulitis has a less aggressive expression profile of the Th1 cytokine IFN-γ and a markedly reduced diabetes incidence. Collectively, these observations demonstrate a disease-promoting role of E2-2 dependent pDCs in the pancreas during autoimmune diabetes in the NOD mouse. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
10
issue
12
publisher
Public Library of Science
external identifiers
  • pmid:26624013
  • wos:000365891600091
  • scopus:84956530874
ISSN
1932-6203
DOI
10.1371/journal.pone.0144090
language
English
LU publication?
yes
id
bc7287a7-d860-4649-891c-413073a2db0a (old id 8505936)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26624013?dopt=Abstract
date added to LUP
2016-01-04 20:13:55
date last changed
2017-09-17 06:14:22
@article{bc7287a7-d860-4649-891c-413073a2db0a,
  abstract     = {Autoimmune diabetes is a consequence of immune-cell infiltration and destruction of pancreatic β-cells in the islets of Langerhans. We analyzed the cellular composition of the insulitic lesions in the autoimmune-prone non-obese diabetic (NOD) mouse and observed a peak in recruitment of plasmacytoid dendritic cells (pDCs) to NOD islets around 8-9 weeks of age. This peak coincides with increased spontaneous expression of type-1-IFN response genes and CpG1585 induced production of IFN-α from NOD islets. The transcription factor E2-2 is specifically required for the maturation of pDCs, and we show that knocking out E2-2 conditionally in CD11c+ cells leads to a reduced recruitment of pDCs to pancreatic islets and reduced CpG1585 induced production of IFN-α during insulitis. As a consequence, insulitis has a less aggressive expression profile of the Th1 cytokine IFN-γ and a markedly reduced diabetes incidence. Collectively, these observations demonstrate a disease-promoting role of E2-2 dependent pDCs in the pancreas during autoimmune diabetes in the NOD mouse.},
  articleno    = {e0144090},
  author       = {Hansen, Lisbeth and Schmidt-Christensen, Anja and Gupta, Shashank and Fransén Pettersson, Nina and Hannibal, Tine and Reizis, Boris and Santamaria, Pere and Holmberg, Dan},
  issn         = {1932-6203},
  language     = {eng},
  month        = {12},
  number       = {12},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {E2-2 Dependent Plasmacytoid Dendritic Cells Control Autoimmune Diabetes.},
  url          = {http://dx.doi.org/10.1371/journal.pone.0144090},
  volume       = {10},
  year         = {2015},
}