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Science 334 (6062): 1561-1565

Copyright © 2011 by the American Association for the Advancement of Science

Natural Aryl Hydrocarbon Receptor Ligands Control Organogenesis of Intestinal Lymphoid Follicles

Elina A. Kiss,1,2,3 Cedric Vonarbourg,1 Stefanie Kopfmann,1 Elias Hobeika,4 Daniela Finke,5 Charlotte Esser,6 Andreas Diefenbach1,2,3,*

Abstract: Innate lymphoid cells (ILC) expressing the transcription factor ROR{gamma}t induce the postnatal formation of intestinal lymphoid follicles and regulate intestinal homeostasis. ROR{gamma}t+ ILC express the aryl hydrocarbon receptor (AhR), a highly conserved, ligand-inducible transcription factor believed to control adaptation of multicellular organisms to environmental challenges. We show that AhR is required for the postnatal expansion of intestinal ROR{gamma}t+ ILC and the formation of intestinal lymphoid follicles. AhR activity within ROR{gamma}t+ ILC could be induced by dietary ligands such as those contained in vegetables of the family Brassicaceae. AhR-deficient mice were highly susceptible to infection with Citrobacter rodentium, a mouse model for attaching and effacing infections. Our results establish a molecular link between nutrients and the formation of immune system components required to maintain intestinal homeostasis and resistance to infections.

1 Institute of Medical Microbiology and Hygiene (IMMH), University of Freiburg Medical Center, Hermann-Herder-Strasse 11, D-79104 Freiburg, Germany.
2 Spemann Graduate School of Biology and Medicine, Albertstrasse 19A, D-79104 Freiburg, Germany.
3 Research Training Group of Organogenesis (GRK1104), Hauptstrasse 1, D-79104 Freiburg, Germany.
4 Max Planck Institute of Immunobiology and Epigenetics, and Department of Molecular Immunology, Faculty of Biology III, University of Freiburg, Stübeweg 51, D-79108 Freiburg, Germany.
5 Developmental Immunology, Department of Biomedicine, University of Basel, Mattenstrasse 28, CH-4058 Basel, Switzerland.
6 Leibniz Research Institute for Environmental Medicine at the Heinrich-Heine-University of Düsseldorf, Auf’m Hennekamp 50, D-40225 Düsseldorf, Germany.

* To whom correspondence should be addressed. E-mail: andreas.diefenbach{at}uniklinik-freiburg.de

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