Dietary and Microbial Oxazoles Induce Intestinal Inflammation by Modulating Aryl Hydrocarbon Receptor Responses
| Autor: | Amadeu Llebaria, Punyanganie S. de Silva, Joana F. Neves, Shankar S. Iyer, Thomas Gensollen, Gurdyal S. Besra, Richard S. Blumberg, Frédéric Collin, Anthony Maxwell, Russell Hauser, Sungwhan F. Oh, R. Balfour Sartor, Amit Gandhi, Jonathan N. Glickman, Carme Serra, Richard Lavin |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Inflammation Biology Article General Biochemistry Genetics and Molecular Biology Pathogenesis Mice 03 medical and health sciences medicine Animals Indoleamine-Pyrrole 2 3 -Dioxygenase RNA Small Interfering Oxazoles Mice Knockout Tryptophan Epithelial Cells Colitis Aryl hydrocarbon receptor Natural killer T cell Intestinal epithelium Diet Interleukin-10 Cell biology Intestines Mice Inbred C57BL Disease Models Animal Interleukin 10 030104 developmental biology Receptors Aryl Hydrocarbon CD1D biology.protein Natural Killer T-Cells RNA Interference Antigens CD1d Signal transduction medicine.symptom Signal Transduction |
| Zdroj: | Iyer, S S, Gensollen, T, Gandhi, A, Oh, S F, Neves, J F, Collin, F, Lavin, R, Serra, C, Glickman, J N, de Silva, P S A, Sartor, R B, Besra, G, Hauser, R, Maxwell, A, Llebaria, A & Blumberg, R S 2018, ' Dietary and Microbial Oxazoles Induce Intestinal Inflammation by Modulating Aryl Hydrocarbon Receptor Responses. ', Cell, vol. 173, no. 5, pp. 1123-1134.e11 . https://doi.org/10.1016/j.cell.2018.04.037 |
| ISSN: | 0092-8674 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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