PMID- 17565376
OWN - NLM
STAT- MEDLINE
DCOM- 20100429
LR  - 20191210
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 2
IP  - 6
DP  - 2007 Jun 13
TI  - CARD15/NOD2 is required for Peyer's patches homeostasis in mice.
PG  - e523
LID - e523
AB  - BACKGROUND: CARD15/NOD2 mutations are associated with susceptibility to Crohn's 
      Disease (CD) and Graft Versus Host Disease (GVHD). CD and GVHD are suspected to 
      be related with the dysfunction of Peyer's patches (PP) and isolated lymphoid 
      follicles (LFs). Using a new mouse model invalidated for Card15/Nod2 (KO), we 
      thus analysed the impact of the gene in these lymphoid formations together with 
      the development of experimental colitis. METHODOLOGY/PRINCIPAL FINDINGS: At weeks 
      4, 12 and 52, the numbers of PPs and LFs were higher in KO mice while no 
      difference was observed at birth. At weeks 4 and 12, the size and cellular 
      composition of PPs were analysed by flow cytometry and immunohistochemistry. PPs 
      of KO mice were larger with an increased proportion of M cells and CD4(+) 
      T-cells. KO mice were also characterised by higher concentrations of TNFalpha, 
      IFNgamma, IL12 and IL4 measured by ELISA. In contrast, little differences were 
      found in the PP-free ileum and the spleen of KO mice. By using chamber 
      experiments, we found that this PP phenotype is associated with an increased of 
      both paracellular permeability and yeast/bacterial translocation. Finally, KO 
      mice were more susceptible to the colitis induced by TNBS. CONCLUSIONS: 
      Card15/Nod2 deficiency induces an abnormal development and function of the PPs 
      characterised by an exaggerated immune response and an increased permeability. 
      These observations provide a comprehensive link between the molecular defect and 
      the Human CARD15/NOD2 associated disorders: CD and GVHD.
FAU - Barreau, Frederick
AU  - Barreau F
AD  - U843, INSERM, Paris, France; UMR-S843, Universite Paris Diderot, Paris, France.
FAU - Meinzer, Ulrich
AU  - Meinzer U
FAU - Chareyre, Fabrice
AU  - Chareyre F
FAU - Berrebi, Dominique
AU  - Berrebi D
FAU - Niwa-Kawakita, Michiko
AU  - Niwa-Kawakita M
FAU - Dussaillant, Monique
AU  - Dussaillant M
FAU - Foligne, Benoit
AU  - Foligne B
FAU - Ollendorff, Vincent
AU  - Ollendorff V
FAU - Heyman, Martine
AU  - Heyman M
FAU - Bonacorsi, Stephane
AU  - Bonacorsi S
FAU - Lesuffleur, Thecla
AU  - Lesuffleur T
FAU - Sterkers, Ghislaine
AU  - Sterkers G
FAU - Giovannini, Marco
AU  - Giovannini M
FAU - Hugot, Jean-Pierre
AU  - Hugot JP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070613
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Nod2 Signaling Adaptor Protein)
RN  - 0 (Nod2 protein, mouse)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Colitis/chemically induced/metabolism/*pathology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Flow Cytometry
MH  - Homeostasis
MH  - Immunoenzyme Techniques
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Nod2 Signaling Adaptor Protein/*physiology
MH  - Peyer's Patches/*metabolism/*pathology
MH  - Phenotype
MH  - RNA, Messenger/genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Spleen/cytology/metabolism
PMC - PMC1885825
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2007/06/15 09:00
MHDA- 2007/06/15 09:01
PMCR- 2007/06/13
CRDT- 2007/06/15 09:00
PHST- 2007/04/19 00:00 [received]
PHST- 2007/04/27 00:00 [accepted]
PHST- 2007/06/15 09:00 [pubmed]
PHST- 2007/06/15 09:01 [medline]
PHST- 2007/06/15 09:00 [entrez]
PHST- 2007/06/13 00:00 [pmc-release]
AID - 07-PONE-RA-01110 [pii]
AID - 10.1371/journal.pone.0000523 [doi]
PST - epublish
SO  - PLoS One. 2007 Jun 13;2(6):e523. doi: 10.1371/journal.pone.0000523.