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Immunology of the gut and liver: a love/hate relationship
  1. D H Adams,
  2. B Eksteen,
  3. S M Curbishley
  1. Liver Research Laboratories, MRC Centre for Immune Regulation, Institute for Biomedical Research, University of Birmingham, Birmingham, UK
  1. Professor D H Adams, Liver Research Laboratories, MRC Centre for Immune Regulation, 5th Floor, Institute for Biomedical Research, Wolfson Drive, Medical School, University of Birmingham, Birmingham B15 2TT, UK; d.h.adams{at}bham.ac.uk

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The gut digests, absorbs and metabolises nutrients whilst also acting as a barrier to pathogens entering from the intestinal lumen. Not all intestinal microbes are harmful and the full development of the gut immune system is shaped by interactions with commensal bacteria in a complex interplay which allows responses to harmless bacteria and nutrients to be suppressed whilst developing protective immune response against pathogens.1 2 Most of these responses occur in the intestinal mucosa and underlying lamina propria; however, transport of nutrients or translocation of pathogens into the portal circulation means that a second level of protection is required in the liver to respond to antigens that evade the gut immune system.3 In addition, pathogens can enter the liver directly via the systemic circulation or from the gut lumen via the biliary epithelium. Immune responses in the gut and to a lesser extent liver are well-described but the mechanisms that control immunological cross-talk between these two linked sites are only beginning to be elucidated.4 They provide insights into the pathogenesis of diseases that affect both sites including infections and inflammatory bowel disease (IBD).

ORGANISATION OF THE GUT IMMUNE SYSTEM

Antigen recognition and acquired intestinal immune responses

The mucosal barrier provides the first line of protection against intestinal pathogens.5 It consists of a mucus layer rich in anti-bacterial substances,6 immunoglobulin A (IgA)7 and commensal bacteria. The epithelial tight junctions prevent bacterial translocation and pathogen-recognition receptors, including toll-like receptors (TLRs) and nucleotide-binding oligomerisation domain (NOD) molecules, sense potentially harmful antigens and trigger innate immune responses.8 9 The critical function of these receptors is demonstrated by the association of Crohn’s disease with mutations that disrupt the functioning of NOD2.10

Antigens that penetrate the mucosal barrier are sampled and processed by specialised antigen presenting cells (APCs) called dendritic cells (DCs) and carried via lymphatics to draining mesenteric lymph nodes …

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