5th Annual BMRP Investigator Meeting - Abstract

CARD15/NOD2 Modulates Peyer’s Patch Phenotype in Mice

Frederick Barreau¹, Ulrich Meinzer^1,2, Fabrice Chareyre³; Dominique Berrebi⁴, Michiko Niwa-Kawakita³, Monique Dussaillant¹, Vincent Ollendorff⁵, Martine Heyman⁶, Stéphane Bonacorsi⁷, Thecla Lesuffleur¹, Ghislaine Sterkers⁸, Marco Giovannini³ and Jean-Pierre Hugot<sup>1,2,a

1</sup>INSERM U763, Programme Avenir, Université Paris7, Hôpital Robert Debré (Paris, France); ²Assistance Publique Hôpitaux de Paris, Service de Gastroentérologie Pédiatrique, Hôpital Robert Debré (Paris, France); ³INSERM U434 ; Fondation Jean Dausset (Paris, France); ⁴Assistance Publique Hôpitaux de Paris, Université Paris7, EA3102, Service d’Anatomie Pathologique, Hopital Robert Debré (Paris, France) ; ⁵Université Paul Cézanne de St. Jérome, IMRN UMR INRA (Marseille, France); ⁶INSERM U793 (Paris, France); ⁷Assistance Publique Hôpitaux de Paris, Service de Microbiologie, Université Paris7, Hôpital Robert Debré (Paris, France) and ⁸Assistance Publique Hôpitaux de Paris, Service d’Immunologie, Université Paris7, (Paris, France)

In humans, CARD15/NOD2 mutations cause susceptibility to Crohn’s disease (CD). CD lesions have been associated with the gut associated lymphoid tissue including Peyer’s patches (PPs) and isolated lymphoid follicles (LFs). We thus analysed the phenotype and function of PPs and LFs in a new mouse model deficient for CARD15/NOD2. CARD15/NOD2-deficient mice exhibited an elevated number of isolated LFs and PPs at weeks 4, 12 and 52, but not at birth. The total number of cells was increased in PP with a higher percentage of CD4⁺ T cells and an elevated number of M cells. Cytokine concentrations (IFN-γ, TNF-α, IL-12 and IL-4) were also higher in knock-out mice. Finally, translocation of E coli and S Aureus were increased in PPs of the CARD15/NOD2 deficient mice but not in the adjacent ileum. As a result, we conclude that NOD2 has a pivotal role in the regulation of lymphoid tissue in gut.

^aPrincipal Investigator