Monomethylfumarate affects polarization of monocyte-derived dendritic cells resulting in down-regulated Th1 lymphocyte responses
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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; Thio, Bing; Walding, Andrew; van Dissel, Jaap T; Nibbering, Peter H.
In: European Journal of Immunology, Vol. 34, No. 2, 02.2004, p. 565-75.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Monomethylfumarate affects polarization of monocyte-derived dendritic cells resulting in down-regulated Th1 lymphocyte responses
AU - Litjens, Nicolle H R
AU - Rademaker, Mirjam
AU - Ravensbergen, Bep
AU - Rea, Delphine
AU - van der Plas, Mariena J A
AU - Thio, Bing
AU - Walding, Andrew
AU - van Dissel, Jaap T
AU - Nibbering, Peter H
PY - 2004/2
Y1 - 2004/2
N2 - 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-gamma. 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, lipo-polysaccharide-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-gamma, 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-kappaB activation in DC. Together, beneficial effects of FAE in psoriasis involve modulation of DC polarization by MMF such that these cells down-regulate IFN-gamma production by Th cells.
AB - 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-gamma. 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, lipo-polysaccharide-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-gamma, 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-kappaB activation in DC. Together, beneficial effects of FAE in psoriasis involve modulation of DC polarization by MMF such that these cells down-regulate IFN-gamma production by Th cells.
KW - Antigens, CD
KW - Cell Differentiation
KW - Cell Polarity
KW - Coculture Techniques
KW - Dendritic Cells
KW - Down-Regulation
KW - Enzyme-Linked Immunosorbent Assay
KW - Flow Cytometry
KW - Fumarates
KW - Humans
KW - Interleukin-10
KW - Interleukin-12
KW - Interleukin-8
KW - Lymphocyte Activation
KW - Maleates
KW - Monocytes
KW - Protein Subunits
KW - Psoriasis
KW - Th1 Cells
KW - Tumor Necrosis Factor-alpha
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1002/eji.200324174
DO - 10.1002/eji.200324174
M3 - Journal article
C2 - 14768062
VL - 34
SP - 565
EP - 575
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 2
ER -
ID: 186451422