Monomethylfumarate affects polarization of monocyte-derived dendritic cells resulting in down-regulated Th1 lymphocyte responses
(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.
(Less)
- author
- 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.
- publishing date
- 2004-02
- 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
-
- pmid:14768062
- scopus:1642329197
- 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
- 2024-09-16 15:32:58
@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<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}}, }