title: Respective Roles of Hematopoietic and Nonhematopoietic Nod2 on the Gut Microbiota and Mucosal Homeostasis.
abstract: BACKGROUND
  NOD2 mutations are associated with Crohn's disease (CD). Both CD (in human) and Nod2 deficiency (in mice) are characterized by increased mucosal CD4 T-cells, an altered permeability and a microbial dysbiosis. However, the respective roles of the gut epithelial and immune compartments on the phenotype are not known.
  
  
  METHODS
  Microbial composition, epithelial peptide secretion, intestinal permeability, and immune cell composition of Peyer patches were studied in Nod2 knock-out mice transplanted with wild-type bone marrow cells and vice versa.
  
  
  RESULTS
  The nonhematopoietic cells control the microbiota composition and epithelial secretion of mucins and antimicrobial peptides. These parameters are correlated with recurrent associations between bacterial species and luminal products. In contrast, Nod2 in the hematopoietic compartment regulates the epithelial permeability and the gut-associated lymphoid tissue independently of the bacterial composition.
  
  
  CONCLUSIONS
  The immune system and the gut permeability in one hand and the microbial and epithelial peptide compositions in the other hand are separate couples of interdependent parameters, both controlled by Nod2 in either the hematopoietic or nonhematopoietic lineages.
authors.affiliation: *Centre de Recherche sur l'inflammation, Université Paris-Diderot Sorbonne Paris-Cité, Paris, France; †INSERM, UMR 1149, Paris, France; ‡Labex Inflamex, Paris, France; §INRA, MICALIS-UMR1319, Jouy-en-Josas, France; ‖AgroParisTech, MICALISUMR1319, Jouy-en-Josas, France; ¶Assistance Publique Hôpitaux de Paris, Hôpital Robert Debré, Paris, France; **INSERM UMR1163, Laboratory of Intestinal Immunity; Paris, France; ††Université Paris Descartes-Sorbonne Paris Cité and Institut Imagine, Paris, France; and ‡‡INSERM, UMR 1220, Institut de Recherche en Santé Digestive, Université de Toulouse, Toulouse, France.
authors.forename: Ziad
authors.initials: Z
authors.lastname: Alnabhani
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hugot
authors.forename: Nicolas
authors.initials: N
authors.lastname: Montcuquet
authors.forename: Karine
authors.initials: K
authors.lastname: Le Roux
authors.forename: Monique
authors.initials: M
authors.lastname: Dussaillant
authors.forename: Maryline
authors.initials: M
authors.lastname: Roy
authors.forename: Marion
authors.initials: M
authors.lastname: Leclerc
authors.forename: Nadine
authors.initials: N
authors.lastname: Cerf-Bensussan
authors.forename: Patricia
authors.initials: P
authors.lastname: Lepage
authors.forename: Frédérick
authors.initials: F
authors.lastname: Barreau
mesh_terms: D000818:Animals; D064806:Dysbiosis / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D000069196:Gastrointestinal Microbiome; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000382:microbiology*; D006706:Homeostasis / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D018345:Mice, Knockout; D053473:Nod2 Signaling Adaptor Protein / Q000502:physiology*
chemical_list: D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse