Basic Science Review
Genetics of the innate immune response in inflammatory bowel disease†
Johan Van Limbergen MD, MRCPCH,
Richard K. Russell MRCPH,
Elaine R. Nimmo BSc, MSc, PhD,
Gwo-Tzer Ho MRCP,
Ian D. Arnott MD,
David C. Wilson MD, FRCPCH,
Jack Satsangi DPhil, FRCPCH,
Corresponding Author
Johan Van Limbergen MD, MRCPCH
Gastrointestinal Unit, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK
Department of Paediatric Gastroenterology and Nutrition, Royal Hospital for Sick Children, Edinburgh, UK EH91LF
Gastrointestinal Unit, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UKSearch for more papers by this authorRichard K. Russell MRCPH
Department of Paediatric Gastroenterology and Nutrition, Royal Hospital for Sick Children, Edinburgh, UK EH91LF
Search for more papers by this authorElaine R. Nimmo BSc, MSc, PhD
Gastrointestinal Unit, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK
Search for more papers by this authorGwo-Tzer Ho MRCP
Gastrointestinal Unit, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK
Search for more papers by this authorIan D. Arnott MD
Gastrointestinal Unit, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK
Search for more papers by this authorDavid C. Wilson MD, FRCPCH
Department of Child Life and Health, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK
Department of Paediatric Gastroenterology and Nutrition, Royal Hospital for Sick Children, Edinburgh, UK EH91LF
Search for more papers by this authorJack Satsangi DPhil, FRCPCH
Gastrointestinal Unit, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK
Search for more papers by this authorJohan Van Limbergen MD, MRCPCH,
Richard K. Russell MRCPH,
Elaine R. Nimmo BSc, MSc, PhD,
Gwo-Tzer Ho MRCP,
Ian D. Arnott MD,
David C. Wilson MD, FRCPCH,
Jack Satsangi DPhil, FRCPCH,
Corresponding Author
Johan Van Limbergen MD, MRCPCH
Gastrointestinal Unit, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK
Department of Paediatric Gastroenterology and Nutrition, Royal Hospital for Sick Children, Edinburgh, UK EH91LF
Gastrointestinal Unit, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UKSearch for more papers by this authorRichard K. Russell MRCPH
Department of Paediatric Gastroenterology and Nutrition, Royal Hospital for Sick Children, Edinburgh, UK EH91LF
Search for more papers by this authorElaine R. Nimmo BSc, MSc, PhD
Gastrointestinal Unit, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK
Search for more papers by this authorGwo-Tzer Ho MRCP
Gastrointestinal Unit, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK
Search for more papers by this authorIan D. Arnott MD
Gastrointestinal Unit, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK
Search for more papers by this authorDavid C. Wilson MD, FRCPCH
Department of Child Life and Health, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK
Department of Paediatric Gastroenterology and Nutrition, Royal Hospital for Sick Children, Edinburgh, UK EH91LF
Search for more papers by this authorJack Satsangi DPhil, FRCPCH
Gastrointestinal Unit, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK
Search for more papers by this author†
The authors declare they have no competing interests.
Abstract
The discovery of nucleotide-binding oligomerization domain 2/caspase recruitment domain-containing protein 15 (NOD2/CARD15) as the first susceptibility gene in Crohn's disease (CD) has shifted the focus of research into the pathogenesis of inflammatory bowel disease (IBD) firmly to the innate immune response and the integrity of the epithelial barrier. The subsequent implication in IBD of variant alleles of OCTN, DLG5, MDR1, and TLRs has provided further support for a new, more complex model of innate immunity function in the gastrointestinal tract. In this review, we examine the recent advances in our understanding of the influence of genetics of the innate immune response on IBD. We will focus on germline variation of genes encoding pathogen-recognition receptors, proteins involved in epithelial homeostasis and secreted antimicrobial proteins.
(Inflamm Bowel Dis 2007)
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