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Monomethylfumarate affects polarization of monocyte-derived dendritic cells resulting in down-regulated Th1 lymphocyte responses

Litjens, Nicolle H R ; Rademaker, Mirjam ; Ravensbergen, Bep ; Rea, Delphine ; van der Plas, Mariena J A LU ; Thio, Bing ; Walding, Andrew ; van Dissel, Jaap T. and Nibbering, Peter H. (2004) In European Journal of Immunology 34(2). p.565-575
Abstract

Psoriasis vulgaris, a type-1 cytokine-mediated chronic skin disease, can be treated successfully with fumaric acid esters (FAE). Beneficial effects of this medication coincided with decreased production of IFN-γ. Since dendritic cells (DC) regulate the differentiation of T helper (Th) cells, this study focussed on effects of monomethylfumarate (MMF, bioactive metabolite of FAE) on polarization of monocyte-derived DC. MMF-incubated, lipopolysaccharide-stimulated DC (MMF-DC) produced dramatically (p<0.05) reduced levels of IL-12p70 and IL-10 (8±4% and 20±4%, respectively) compared to control DC. MMF-DC were mature. MMF affected polarization of DC irrespective of polarization factor(s) and ligands for the various Toll-like receptors... (More)

Psoriasis vulgaris, a type-1 cytokine-mediated chronic skin disease, can be treated successfully with fumaric acid esters (FAE). Beneficial effects of this medication coincided with decreased production of IFN-γ. Since dendritic cells (DC) regulate the differentiation of T helper (Th) cells, this study focussed on effects of monomethylfumarate (MMF, bioactive metabolite of FAE) on polarization of monocyte-derived DC. MMF-incubated, lipopolysaccharide-stimulated DC (MMF-DC) produced dramatically (p<0.05) reduced levels of IL-12p70 and IL-10 (8±4% and 20±4%, respectively) compared to control DC. MMF-DC were mature. MMF affected polarization of DC irrespective of polarization factor(s) and ligands for the various Toll-like receptors used. Coculture of MMF-DC with naive and primed allogenous Th cells resulted in lymphocytes producing less IFN-γ, i.e. 59% and 54% of that by the respective Th cells cocultured with control DC. IL-4 production by primed, but not naive Th cells cocultured with MMF-DC was decreased as compared to cocultures with control DC. IL-10 production by naive and primed Th cells cocultured with MMF-DC and control DC did not differ. In addition, MMF inhibited LPS-induced NF-κB activation in DC. Together, beneficial effects of FAE in psoriasis involve modulation of DC polarization by MMF such that these cells down-regulate IFN-γ production by Th cells.

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author
; ; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
Cytokines, Dendritic cells, Fumarates, Lymphocytes
in
European Journal of Immunology
volume
34
issue
2
pages
11 pages
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:1642329197
  • pmid:14768062
ISSN
0014-2980
DOI
10.1002/eji.200324174
language
English
LU publication?
no
id
7c695068-341c-4128-8672-6a5f52ec41e2
date added to LUP
2018-01-15 10:58:57
date last changed
2025-01-08 03:37:21
@article{7c695068-341c-4128-8672-6a5f52ec41e2,
  abstract     = {{<p>Psoriasis vulgaris, a type-1 cytokine-mediated chronic skin disease, can be treated successfully with fumaric acid esters (FAE). Beneficial effects of this medication coincided with decreased production of IFN-γ. Since dendritic cells (DC) regulate the differentiation of T helper (Th) cells, this study focussed on effects of monomethylfumarate (MMF, bioactive metabolite of FAE) on polarization of monocyte-derived DC. MMF-incubated, lipopolysaccharide-stimulated DC (MMF-DC) produced dramatically (p&lt;0.05) reduced levels of IL-12p70 and IL-10 (8±4% and 20±4%, respectively) compared to control DC. MMF-DC were mature. MMF affected polarization of DC irrespective of polarization factor(s) and ligands for the various Toll-like receptors used. Coculture of MMF-DC with naive and primed allogenous Th cells resulted in lymphocytes producing less IFN-γ, i.e. 59% and 54% of that by the respective Th cells cocultured with control DC. IL-4 production by primed, but not naive Th cells cocultured with MMF-DC was decreased as compared to cocultures with control DC. IL-10 production by naive and primed Th cells cocultured with MMF-DC and control DC did not differ. In addition, MMF inhibited LPS-induced NF-κB activation in DC. Together, beneficial effects of FAE in psoriasis involve modulation of DC polarization by MMF such that these cells down-regulate IFN-γ production by Th cells.</p>}},
  author       = {{Litjens, Nicolle H R and Rademaker, Mirjam and Ravensbergen, Bep and Rea, Delphine and van der Plas, Mariena J A and Thio, Bing and Walding, Andrew and van Dissel, Jaap T. and Nibbering, Peter H.}},
  issn         = {{0014-2980}},
  keywords     = {{Cytokines; Dendritic cells; Fumarates; Lymphocytes}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{565--575}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{European Journal of Immunology}},
  title        = {{Monomethylfumarate affects polarization of monocyte-derived dendritic cells resulting in down-regulated Th1 lymphocyte responses}},
  url          = {{http://dx.doi.org/10.1002/eji.200324174}},
  doi          = {{10.1002/eji.200324174}},
  volume       = {{34}},
  year         = {{2004}},
}