Impaired dendritic cell function in Crohn’s disease patients with NOD2 3020insC mutation

The nucleotide oligomerization domain 2 (NOD2) 3020insC (NOD2fs) mutation increases susceptibility to Crohn’s disease (CD), but the mechanism remains controversial. Loss‐of‐function and gain‐of‐function phenotypes have been described as a result of NOD2fs. Here, we show that dendritic cells (DC) der...

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Bibliographic Details
Published in:Journal of leukocyte biology 2006-04, Vol.79 (4), p.860-866
Main Authors: Kramer, Matthijs, Netea, Mihai G., Jong, Dirk J., Kullberg, Bart Jan, Adema, Gosse J.
Format: Article
Language:English
Subjects:
Acetylmuramyl-Alanyl-Isoglutamine - pharmacology
Adult
Crohn Disease - genetics
Crohn Disease - immunology
cytokines
Cytokines - biosynthesis
Dendritic Cells - drug effects
Dendritic Cells - immunology
Female
human
Humans
Interleukin-10 - pharmacology
Intracellular Signaling Peptides and Proteins - genetics
Ligands
Male
Middle Aged
Mutation
Nod2 Signaling Adaptor Protein
Phenotype
Toll-Like Receptors - immunology
Toll‐like receptor
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Summary:The nucleotide oligomerization domain 2 (NOD2) 3020insC (NOD2fs) mutation increases susceptibility to Crohn’s disease (CD), but the mechanism remains controversial. Loss‐of‐function and gain‐of‐function phenotypes have been described as a result of NOD2fs. Here, we show that dendritic cells (DC) derived from CD patients homozygous for this mutation respond normally to purified Toll‐like receptor (TLR) ligands but fail to up‐regulate the costimulatory molecules CD80 and CD86 in response to the NOD2 ligand muramyl dipeptide (MDP). Moreover, they lack MDP‐induced enhancement of TLR‐mediated tumor necrosis factor α, interleukin (IL)‐12, and IL‐10 production, which is observed in control DC with intact NOD2. These data indicate that the NOD2fs mutation results in a loss‐of‐function phenotype in human myeloid DC and imply decreased immune regulation by IL‐10 as a possible mechanism for this mutation in CD.
ISSN:0741-5400
1938-3673
DOI:10.1189/jlb.0805484