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The Relationship Between miR-29, NOD2 and Crohn’s Disease

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MicroRNAs and Other Non-Coding RNAs in Inflammation

Part of the book series: Progress in Inflammation Research ((PIR))

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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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Authors and Affiliations

  1. Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, OX3 9DU, UK

    Oliver Brain & Alison Simmons

  2. MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DS, UK

    Alison Simmons

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  1. Oliver Brain
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Correspondence to Oliver Brain .

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Editors and Affiliations

  1. Respiratory Research, Department of Medicine, Royal College of Surgeon in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland

    Catherine M. Greene

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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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