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Impaired dendritic cell function in Crohn’s disease patients with NOD2 3020insC mutation
Author(s) -
Kramer Matthijs,
Netea Mihai G.,
Jong Dirk J.,
Kullberg Bart Jan,
Adema Gosse J.
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0805484
Subject(s) - nod2 , muramyl dipeptide , biology , mutation , cd86 , cd80 , immune system , dendritic cell , phenotype , tumor necrosis factor alpha , toll like receptor , immunology , t cell , cancer research , genetics , innate immune system , gene , in vitro , cd40 , cytotoxic t cell
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.