Advanced

IL-10-dependent partial refractoriness to Toll-like receptor stimulation modulates gut mucosal dendritic cell function

Monteleone, Ivan; Platt, Andrew M; Jaensson Gyllenbäck, Elin LU ; Agace, William LU and Mowat, Allan McI (2008) In European Journal of Immunology 38(6). p.1533-1547
Abstract
The default response of the intestinal immune system to most antigens is the induction of immunological tolerance, which is difficult to reconcile with the constant exposure to ligands for TLR and other pattern recognition receptors. We showed previously that dendritic cells (DC) from the lamina propria of normal mouse intestine may be inherently tolerogenic and here we have explored how this might relate to the expression and function of Toll-like receptors (TLR). Lamina propria (LP) DC showed higher levels of TLR 2, 3, 4 and 9 protein expression than spleen and MLN DC, with most TLR-expressing DC in the gut being CD11c(lo), class II MHClo, CD103(-), CD11b(-) and F4/80(-). TLR expression by lamina propria DC was low in the upper small... (More)
The default response of the intestinal immune system to most antigens is the induction of immunological tolerance, which is difficult to reconcile with the constant exposure to ligands for TLR and other pattern recognition receptors. We showed previously that dendritic cells (DC) from the lamina propria of normal mouse intestine may be inherently tolerogenic and here we have explored how this might relate to the expression and function of Toll-like receptors (TLR). Lamina propria (LP) DC showed higher levels of TLR 2, 3, 4 and 9 protein expression than spleen and MLN DC, with most TLR-expressing DC in the gut being CD11c(lo), class II MHClo, CD103(-), CD11b(-) and F4/80(-). TLR expression by lamina propria DC was low in the upper small intestine and higher in distal small intestine and colon. Freshly isolated lamina propria DC expressed some CD40, CD80, CD86 and functional CCR7. These were up-regulated on CD11c(lo), but not on CD1lc(hi) LP DC by stimulation via TLR. However, there was little induction of IL-12 by either subset in response to TLR ligation. This was associated with constitutive IL-10 production and was reversed by blocking IL-10 function. Thus, IL-10 may maintain LP DC in a partially unresponsive state to TLR ligation, allowing them to have a critical role in immune homeostasis in the gut. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
TLR, IL-10, tolerance, dendritic cells, mucosa
in
European Journal of Immunology
volume
38
issue
6
pages
1533 - 1547
publisher
John Wiley & Sons
external identifiers
  • wos:000256762400009
  • scopus:47149101644
ISSN
1521-4141
DOI
10.1002/eji.200737909
language
English
LU publication?
yes
id
52b48dfc-2b4d-4150-9450-14a657e7bbab (old id 1191420)
date added to LUP
2008-09-08 15:54:47
date last changed
2017-10-22 03:54:10
@article{52b48dfc-2b4d-4150-9450-14a657e7bbab,
  abstract     = {The default response of the intestinal immune system to most antigens is the induction of immunological tolerance, which is difficult to reconcile with the constant exposure to ligands for TLR and other pattern recognition receptors. We showed previously that dendritic cells (DC) from the lamina propria of normal mouse intestine may be inherently tolerogenic and here we have explored how this might relate to the expression and function of Toll-like receptors (TLR). Lamina propria (LP) DC showed higher levels of TLR 2, 3, 4 and 9 protein expression than spleen and MLN DC, with most TLR-expressing DC in the gut being CD11c(lo), class II MHClo, CD103(-), CD11b(-) and F4/80(-). TLR expression by lamina propria DC was low in the upper small intestine and higher in distal small intestine and colon. Freshly isolated lamina propria DC expressed some CD40, CD80, CD86 and functional CCR7. These were up-regulated on CD11c(lo), but not on CD1lc(hi) LP DC by stimulation via TLR. However, there was little induction of IL-12 by either subset in response to TLR ligation. This was associated with constitutive IL-10 production and was reversed by blocking IL-10 function. Thus, IL-10 may maintain LP DC in a partially unresponsive state to TLR ligation, allowing them to have a critical role in immune homeostasis in the gut.},
  author       = {Monteleone, Ivan and Platt, Andrew M and Jaensson Gyllenbäck, Elin and Agace, William and Mowat, Allan McI},
  issn         = {1521-4141},
  keyword      = {TLR,IL-10,tolerance,dendritic cells,mucosa},
  language     = {eng},
  number       = {6},
  pages        = {1533--1547},
  publisher    = {John Wiley & Sons},
  series       = {European Journal of Immunology},
  title        = {IL-10-dependent partial refractoriness to Toll-like receptor stimulation modulates gut mucosal dendritic cell function},
  url          = {http://dx.doi.org/10.1002/eji.200737909},
  volume       = {38},
  year         = {2008},
}