Dietary and Microbial Oxazoles Induce Intestinal Inflammation by Modulating Aryl Hydrocarbon Receptor Responses

Shankar S. Iyer, Thomas Gensollen, Amit Gandhi, Sungwhan F. Oh, Joana F. Neves, Frederic Collin, Richard Lavin, Carme Serra, Jonathan Glickman, Punyanganie S. A. de Silva, R. Balfour Sartor, Gurdyal Besra, Russell Hauser, Anthony Maxwell, Amadeu Llebaria, Richard S. Blumberg

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)
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Abstract

Genome-wide association studies have identified risk loci associated with the development of inflammatory bowel disease, while epidemiological studies have emphasized that pathogenesis likely involves host interactions with environmental elements whose source and structure need to be defined. Here, we identify a class of compounds derived from dietary, microbial, and industrial sources that are characterized by the presence of a five-membered oxazole ring and induce CD1d-dependent intestinal inflammation. We observe that minimal oxazole structures modulate natural killer T cell-dependent inflammation by regulating lipid antigen presentation by CD1d on intestinal epithelial cells (IECs). CD1d-restricted production of interleukin 10 by IECs is limited through activity of the aryl hydrocarbon receptor (AhR) pathway in response to oxazole induction of tryptophan metabolites. As such, the depletion of the AhR in the intestinal epithelium abrogates oxazole-induced inflammation. In summary, we identify environmentally derived oxazoles as triggers of CD1d-dependent intestinal inflammatory responses that occur via activation of the AhR in the intestinal epithelium.

Original languageEnglish
Pages (from-to)1123-1134.e11
JournalCell
Volume173
Issue number5
DOIs
Publication statusPublished - 17 May 2018

Keywords

  • inflammatory bowel disease
  • natural killer T cell
  • mucosal inflammation
  • microbiota
  • microcin
  • oxazole
  • aryl hydrocarbon receptor
  • CD1d
  • intestinal epithelial cell
  • tryptophan
  • indoleamine 2,3-dioxygenase

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