Antimicrobial peptides in inflammatory bowel disease

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Scopus citations

Abstract

Antimicrobial peptides are one of the most ancient forms of host defense in nature. In the mammalian intestine, clear and compelling evidence supports that antimicrobial peptides play two fundamental roles: protection from enteric pathogens and shaping the composition of the colonizing microbiota. These functions likely hold relevance to host–microbe interactions that underlie inflammatory bowel disease (IBD) pathogenesis. Epithelial cells of the human intestine express a collection of antimicrobial peptides that have overlapping and complementary activities. These peptides have substantial influence on the intestinal microbiota. Prevailing theories on the pathogenesis of IBD invoke a role for the detrimental effects of intestinal microbes in the initiation and/or propagation of mucosal inflammation. The most abundant antimicrobial peptides in the human intestine are α(alpha)-defensin peptides, most notably human defensin (HD)–5 and HD6. Other abundant polypeptides, which are larger in size but with fundamentally similar physiological roles, are lysozyme, secretory phospholipase A2, and the C–type lectin RegIIIα. Specialized epithelial cells named Paneth cells produce and secrete vast quantities of these various antimicrobial peptides. Evidence supports that reduced Paneth cell α–defensin expression may be a key factor in the pathogenesis of ileal Crohn's disease, a subgroup of IBD. Furthermore, several susceptibility genes for IBD may manifest their effects, in part, through compromise of Paneth cell antimicrobial peptide production or function. For example, the microbial sensor NOD–2, the autophagy protein ATG16L1, the endoplasmic reticulum stress responder XBP–1, the calcium–dependent potassium channel KCa3.1 and the transcription factor TCF4 are all important in Paneth cell function. While not proven, it is likely that the Paneth cell dysfunction, which may result from variants in genes encoding these or other Paneth cell proteins, may substantially contribute to IBD pathogenesis.

Original languageEnglish (US)
Title of host publicationCrohn's Disease and Ulcerative Colitis: From Epidemiology and Immunobiology to a Rational Diagnostic and Therapeutic Approach
PublisherSpringer US
Pages119-132
Number of pages14
ISBN (Electronic)9781461409984
ISBN (Print)9781461409977
DOIs
StatePublished - Jan 1 2012

Keywords

  • Antimicrobial peptide
  • Candidatus arthromitis
  • Crohn's disease
  • Cryptdin-related sequences
  • Dysbiosis
  • Hepatocarcinoma-intestine-pancreas
  • KCa 3.1
  • Lysozyme
  • Matrix metalloproteinase-7
  • Microbiota
  • NOD2
  • Pancreatitis-associated protein
  • Paneth cell
  • PLA2
  • Salmonella
  • Secretory phospholipase
  • Segmented filamentous bacteria
  • Tcf-4
  • Ulcerative colitis
  • X-box-binding protein 1
  • α(alpha)-Defensin

ASJC Scopus subject areas

  • Medicine(all)

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  • Cite this

    Bevins, C. L. (2012). Antimicrobial peptides in inflammatory bowel disease. In Crohn's Disease and Ulcerative Colitis: From Epidemiology and Immunobiology to a Rational Diagnostic and Therapeutic Approach (pp. 119-132). Springer US. https://doi.org/10.1007/978-1-4614-0998-4_8