Abstract
Crohn’s disease (CD) is a chronic inflammatory bowel disease with a complex aetiology that includes genetic susceptibility and the gastrointestinal microbiome and results in an aberrant Th17 inflammatory response. NOD2 is an intracellular sensor that responds to bacterial cell wall peptidoglycan and contributes to immune defense. Polymorphisms in the NOD2 gene predispose to Crohn’s disease, with the largest effect of any of the known genetic risk factors. We have found that wild-type NOD2 controls the expression of miR-29 in human dendritic cells (DCs). miR-29 regulates the expression of a number of immune mediators including the IL-23 cytokine subunits IL-12p40 and IL-23p19. CD patient DCs expressing NOD2 polymorphisms fail to induce miR-29 and show enhanced IL-12p40 release on exposure to adherent invasive E. coli. Moreover in a murine model deficient in miR-29, a more severe Th17-driven colitis is established after DSS administration. Therefore, we suggest that the loss of miR-29-mediated immunoregulation in CD-variant NOD2 DCs contributes to elevated IL-23 and aberrant Th17 response in this disease.
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Abbreviations
- AIEC:
-
Adherent-invasive Escherichia coli
- APC:
-
Antigen presenting cell
- ATG16L1:
-
Autophagy related 16-like 1
- CARD15:
-
Caspase recruitment domain family member 15
- CD:
-
Crohn’s disease
- Chr:
-
Chromosome
- CLR:
-
C-type lectin receptors
- DAMP:
-
Damage-associated molecular pattern
- DC:
-
Dendritic cell
- DSS:
-
Dextran sodium sulphate
- F. prau :
-
Faecalibacterium prausnitzii
- Foxp3:
-
Forkhead box P3
- GI:
-
Gastrointestinal
- GWAS:
-
Genome-wide association study
- HD:
-
Human defensin
- IBD:
-
Inflammatory bowel disease
- IFN:
-
Interferon
- IL:
-
Interleukin
- IL-12B:
-
Interleukin 12B/IL-12p40
- IL-23R:
-
Interleukin-23 receptor
- IRGM:
-
Immunity-related GTPase family, M
- JAK2:
-
Janus kinase 2
- KO:
-
Knock-out
- LPS:
-
Lipopolysaccharide
- LRR:
-
Leucine-rich repeat
- MDDC:
-
Monocyte-derived dendritic cell
- MDP:
-
Muramyl dipeptide
- miR:
-
microRNA
- MyD88:
-
Myeloid differentiation primary response gene 88
- NFκB:
-
Nuclear factor kappa B
- NK:
-
Natural killer
- NLR:
-
NOD-like receptor
- NOD2:
-
Nucleotide-binding oligomerisation domain containing 2
- Pam3CSK4 :
-
Synthetic triacylated lipoprotein—TLR1/2 ligand
- PAMP:
-
Pathogen-associated molecular pattern
- PCR:
-
Polymerase chain reaction
- PGN:
-
Peptidoglycan
- PRR:
-
Pattern recognition receptor
- qPCR:
-
Quantitative polymerase chain reaction
- RIPK-2:
-
Receptor-interacting protein kinase 2
- RORγt:
-
RAR-related orphan receptor gamma
- STAT3:
-
Signal transducer and activator of transcription 3
- T-bet:
-
T-box transcription factor
- Th1/17:
-
T helper 1/17
- TLR:
-
Toll-like receptor
- TNF:
-
Tumour necrosis factor
- Wnt:
-
Wingless
- WT:
-
Wild-type
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Brain, O., Simmons, A. (2015). The Relationship Between miR-29, NOD2 and Crohn’s Disease. In: Greene, C. (eds) MicroRNAs and Other Non-Coding RNAs in Inflammation. Progress in Inflammation Research. Springer, Cham. https://doi.org/10.1007/978-3-319-13689-9_10
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DOI: https://doi.org/10.1007/978-3-319-13689-9_10
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