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A gluten free diet lowers NKG2D and ligand expression in BALB/c and NOD mice.

Adlercreutz, Emma LU ; Weile, Christian ; Larsen, Jesper ; Engkilde, Kåre ; Agardh, Daniel LU ; Buschard, Karsten and Antvorskov, Julie C (2014) In Clinical and Experimental Immunology 177(2). p.391-403
Abstract
The interplay between diet and immune-parameters which could affect type 1 diabetes (T1D) pathogenesis is not sufficiently clarified. Intestinal upregulation of the activating receptor NKG2D(CD314) and its ligands is a hallmark of celiac disease (CD). However, the direct effect of gluten on NKG2D expression is not known. We studied, by FACS (lymphoid tissues) and RT-qPCR (intestine and pancreatic islets), if a gluten-free diet from 4 weeks (GF diet) or a gluten-free diet introduced in breeding pairs (SGF diet), induces changes in NKG2D expression on NK-cells DX5(+) (CD49b) and CD8(+) T-cells, as well as in intestinal and islet levels of NKG2D and ligands in BALB/c and NOD mice. Gluten-free NOD mice had lower insulitis (p<0.0001).... (More)
The interplay between diet and immune-parameters which could affect type 1 diabetes (T1D) pathogenesis is not sufficiently clarified. Intestinal upregulation of the activating receptor NKG2D(CD314) and its ligands is a hallmark of celiac disease (CD). However, the direct effect of gluten on NKG2D expression is not known. We studied, by FACS (lymphoid tissues) and RT-qPCR (intestine and pancreatic islets), if a gluten-free diet from 4 weeks (GF diet) or a gluten-free diet introduced in breeding pairs (SGF diet), induces changes in NKG2D expression on NK-cells DX5(+) (CD49b) and CD8(+) T-cells, as well as in intestinal and islet levels of NKG2D and ligands in BALB/c and NOD mice. Gluten-free NOD mice had lower insulitis (p<0.0001). Gluten-free NOD mice had reduced expression of NKG2D on DX5(+) NK-cells in spleen and auricular lymph nodes (p<0.05) and on CD8(+) T-cells in pancreas associated lymph nodes (p=0.04). Moreover, the level of CD71 on DX5(+) NK-cells and CD8(+) T-cells (p<0.005) was markedly reduced. GF and SGF mice had reduced expression of NKG2D and DX5 mRNA in intestine (p<0.05). Differences in intestinal mRNA expression were found in mice of 8, 13 and 20 weeks. Intestinal expression of NKG2D ligands was reduced in SGF mice with lower expression of all ligands. In isolated islets, a SGF diet induced a higher expression of specific NKG2D ligands. Our data shows that a gluten-free diet reduces the level of NKG2D and the expression of NKG2D ligands. These immunological changes may contribute to the lower T1D incidence associated with a gluten-free diet. (Less)
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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Clinical and Experimental Immunology
volume
177
issue
2
pages
391 - 403
publisher
British Society for Immunology
external identifiers
  • pmid:24673402
  • wos:000339480700003
  • scopus:84904012030
  • pmid:24673402
ISSN
0009-9104
DOI
10.1111/cei.12340
language
English
LU publication?
yes
id
ee5ffd2f-e685-41d1-85cf-971b9932d05b (old id 4379596)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24673402?dopt=Abstract
date added to LUP
2016-04-01 10:32:48
date last changed
2022-01-26 00:17:02
@article{ee5ffd2f-e685-41d1-85cf-971b9932d05b,
  abstract     = {{The interplay between diet and immune-parameters which could affect type 1 diabetes (T1D) pathogenesis is not sufficiently clarified. Intestinal upregulation of the activating receptor NKG2D(CD314) and its ligands is a hallmark of celiac disease (CD). However, the direct effect of gluten on NKG2D expression is not known. We studied, by FACS (lymphoid tissues) and RT-qPCR (intestine and pancreatic islets), if a gluten-free diet from 4 weeks (GF diet) or a gluten-free diet introduced in breeding pairs (SGF diet), induces changes in NKG2D expression on NK-cells DX5(+) (CD49b) and CD8(+) T-cells, as well as in intestinal and islet levels of NKG2D and ligands in BALB/c and NOD mice. Gluten-free NOD mice had lower insulitis (p&lt;0.0001). Gluten-free NOD mice had reduced expression of NKG2D on DX5(+) NK-cells in spleen and auricular lymph nodes (p&lt;0.05) and on CD8(+) T-cells in pancreas associated lymph nodes (p=0.04). Moreover, the level of CD71 on DX5(+) NK-cells and CD8(+) T-cells (p&lt;0.005) was markedly reduced. GF and SGF mice had reduced expression of NKG2D and DX5 mRNA in intestine (p&lt;0.05). Differences in intestinal mRNA expression were found in mice of 8, 13 and 20 weeks. Intestinal expression of NKG2D ligands was reduced in SGF mice with lower expression of all ligands. In isolated islets, a SGF diet induced a higher expression of specific NKG2D ligands. Our data shows that a gluten-free diet reduces the level of NKG2D and the expression of NKG2D ligands. These immunological changes may contribute to the lower T1D incidence associated with a gluten-free diet.}},
  author       = {{Adlercreutz, Emma and Weile, Christian and Larsen, Jesper and Engkilde, Kåre and Agardh, Daniel and Buschard, Karsten and Antvorskov, Julie C}},
  issn         = {{0009-9104}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{391--403}},
  publisher    = {{British Society for Immunology}},
  series       = {{Clinical and Experimental Immunology}},
  title        = {{A gluten free diet lowers NKG2D and ligand expression in BALB/c and NOD mice.}},
  url          = {{http://dx.doi.org/10.1111/cei.12340}},
  doi          = {{10.1111/cei.12340}},
  volume       = {{177}},
  year         = {{2014}},
}