IL-10-dependent partial refractoriness to Toll-like receptor stimulation modulates gut mucosal dendritic cell function
(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:
https://lup.lub.lu.se/record/1191420
- author
- Monteleone, Ivan ; Platt, Andrew M ; Jaensson Gyllenbäck, Elin LU ; Agace, William LU and Mowat, Allan McI
- organization
- publishing date
- 2008
- 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 Inc.
- 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
- 2016-04-01 12:28:27
- date last changed
- 2022-04-05 22:49:30
@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}}, keywords = {{TLR; IL-10; tolerance; dendritic cells; mucosa}}, language = {{eng}}, number = {{6}}, pages = {{1533--1547}}, publisher = {{John Wiley & Sons Inc.}}, 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}}, doi = {{10.1002/eji.200737909}}, volume = {{38}}, year = {{2008}}, }