Title: Monocyte-derived dendritic cells from Crohn patients show differential NOD2/CARD15-dependent immune responses to bacteria
Authors: Salucci, Valentina ×
Rimoldi, Monica
Penati, Chiara
Sampietro, Gianluca M
van Duist, Marjan Maria
Matteoli, Gianluca
Saibeni, Simone
Vecchi, Maurizio
Ardizzone, Sandro
Porro, Gabriele Bianchi
Rescigno, Maria #
Issue Date: Jun-2008
Series Title: Inflammatory bowel diseases vol:14 issue:6 pages:812-8
Abstract: BACKGROUND: Three common mutations in the NOD2/CARD15 gene are strongly associated with Crohn's disease (CD). NOD2 is an intracellular receptor of muramyl dipeptide (MDP), a component of peptidoglycan present in the cell wall of gram-positive (G+) and gram-negative (G-) bacteria. METHODS: We generated monocyte-derived dendritic cells (MoDCs) from CD patients mutated or not for CARD15 (n = 53) or from healthy donors (n = 12) and analyzed their activation in response to live Salmonella typhimurium as a model of pathogenic G- bacteria. RESULTS: MoDCs carrying the L1007fs mutation, although phenotypically activated by bacteria, produced a significantly reduced amount of tested cytokines. MoDCs carrying R702W or compound G908R/R702W NOD2 mutations displayed an increased basal level of IL-8 release. After a bacterial encounter, these cells were phenotypically activated and produced levels of cytokines similar to healthy controls. Interestingly, although L1007fs/WT mutations conferred reduced production of cytokines, including IL-12, these cells were perfectly capable of inducing T-cell polarization toward the Th1 phenotype. CONCLUSIONS: NOD2 mutations affect the basal characteristics of MoDCs and their response to G- bacteria differently. MoDCs could be involved in CD onset because they have defects in releasing inflammatory cytokines and in polarizing T-cell responses.
ISSN: 1078-0998
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Translational Research in GastroIntestinal Disorders
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science