Genetic deletion of the bacterial sensor NOD2 improves murine Crohn's disease-like ileitis independent of functional dysbiosis.
Although genetic polymorphisms in NOD2 (nucleotide-binding oligomerization domain-containing 2) have been associated with the pathogenesis of Crohn's disease (CD), little is known regarding the role of wild-type (WT) NOD2 in the gut. To date, most murine studies addressing the role of WT Nod2 h...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Nature Publishing Group
2016
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| _version_ | 1797102165085388800 |
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| author | Corridoni, D Rodriguez-Palacios, A Di Stefano, G Di Martino, L Antonopoulos, D Chang, E Arseneau, K Pizarro, T Cominelli, F |
| author_facet | Corridoni, D Rodriguez-Palacios, A Di Stefano, G Di Martino, L Antonopoulos, D Chang, E Arseneau, K Pizarro, T Cominelli, F |
| author_sort | Corridoni, D |
| collection | OXFORD |
| description | Although genetic polymorphisms in NOD2 (nucleotide-binding oligomerization domain-containing 2) have been associated with the pathogenesis of Crohn's disease (CD), little is known regarding the role of wild-type (WT) NOD2 in the gut. To date, most murine studies addressing the role of WT Nod2 have been conducted using healthy (ileitis/colitis-free) mouse strains. Here, we evaluated the effects of Nod2 deletion in a murine model of spontaneous ileitis, i.e., the SAMP1Yit/Fc (SAMP) strain, which closely resembles CD. Remarkably, Nod2 deletion improved both chronic cobblestone ileitis (by 50% assessed, as the % of abnormal mucosa at 24 wks of age), as well as acute dextran sodium sulfate (DSS) colitis. Mechanistically, Th2 cytokine production and Th2-transcription factor activation (i.e., STAT6 phosphorylation) were reduced. Microbiologically, the effects of Nod2 deletion appeared independent of fecal microbiota composition and function, assessed by 16S rRNA and metatranscriptomics. Our findings indicate that pharmacological blockade of NOD2 signaling in humans could improve health in Th2-driven chronic intestinal inflammation. |
| first_indexed | 2024-03-07T06:02:04Z |
| format | Journal article |
| id | oxford-uuid:ec89f074-24e9-4abf-b021-70f379ef0bff |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:02:04Z |
| publishDate | 2016 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:ec89f074-24e9-4abf-b021-70f379ef0bff2022-03-27T11:18:25ZGenetic deletion of the bacterial sensor NOD2 improves murine Crohn's disease-like ileitis independent of functional dysbiosis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ec89f074-24e9-4abf-b021-70f379ef0bffEnglishSymplectic Elements at OxfordNature Publishing Group2016Corridoni, DRodriguez-Palacios, ADi Stefano, GDi Martino, LAntonopoulos, DChang, EArseneau, KPizarro, TCominelli, FAlthough genetic polymorphisms in NOD2 (nucleotide-binding oligomerization domain-containing 2) have been associated with the pathogenesis of Crohn's disease (CD), little is known regarding the role of wild-type (WT) NOD2 in the gut. To date, most murine studies addressing the role of WT Nod2 have been conducted using healthy (ileitis/colitis-free) mouse strains. Here, we evaluated the effects of Nod2 deletion in a murine model of spontaneous ileitis, i.e., the SAMP1Yit/Fc (SAMP) strain, which closely resembles CD. Remarkably, Nod2 deletion improved both chronic cobblestone ileitis (by 50% assessed, as the % of abnormal mucosa at 24 wks of age), as well as acute dextran sodium sulfate (DSS) colitis. Mechanistically, Th2 cytokine production and Th2-transcription factor activation (i.e., STAT6 phosphorylation) were reduced. Microbiologically, the effects of Nod2 deletion appeared independent of fecal microbiota composition and function, assessed by 16S rRNA and metatranscriptomics. Our findings indicate that pharmacological blockade of NOD2 signaling in humans could improve health in Th2-driven chronic intestinal inflammation. |
| spellingShingle | Corridoni, D Rodriguez-Palacios, A Di Stefano, G Di Martino, L Antonopoulos, D Chang, E Arseneau, K Pizarro, T Cominelli, F Genetic deletion of the bacterial sensor NOD2 improves murine Crohn's disease-like ileitis independent of functional dysbiosis. |
| title | Genetic deletion of the bacterial sensor NOD2 improves murine Crohn's disease-like ileitis independent of functional dysbiosis. |
| title_full | Genetic deletion of the bacterial sensor NOD2 improves murine Crohn's disease-like ileitis independent of functional dysbiosis. |
| title_fullStr | Genetic deletion of the bacterial sensor NOD2 improves murine Crohn's disease-like ileitis independent of functional dysbiosis. |
| title_full_unstemmed | Genetic deletion of the bacterial sensor NOD2 improves murine Crohn's disease-like ileitis independent of functional dysbiosis. |
| title_short | Genetic deletion of the bacterial sensor NOD2 improves murine Crohn's disease-like ileitis independent of functional dysbiosis. |
| title_sort | genetic deletion of the bacterial sensor nod2 improves murine crohn s disease like ileitis independent of functional dysbiosis |
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