Ziad Alnabhani1, Jean-Pierre Hugot, Nicolas Montcuquet, Karine Le Roux, Monique Dussaillant, Maryline Roy, Marion Leclerc, Nadine Cerf-Bensussan, Patricia Lepage, Frédérick Barreau. 1. *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.
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.
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: Thomas Secher; Sahar Kassem; Mehdi Benamar; Isabelle Bernard; Michele Boury; Frederick Barreau; Eric Oswald; Abdelhadi Saoudi Journal: Front Immunol Date: 2017-09-14 Impact factor: 7.561
Authors: A Butera; M Di Paola; L Pavarini; F Strati; M Pindo; M Sanchez; D Cavalieri; M Boirivant; C De Filippo Journal: Sci Rep Date: 2018-09-24 Impact factor: 4.379