Aryl hydrocarbon receptor

Intestinal homeostasis results from a complex mutualism between gut microbiota and host cells. Defining the molecular network regulating such mutualism is currently of increasing interest, as its deregulation is reported to lead to increased susceptibility to infections, chronic inflammatory bowel diseases and cancer. Until now, the focus has been on the mechanism, by which the composition of indigenous microbiota shapes the immune system. In a recent study, we have shown that dietary compounds have also the ability to affect innate immune system. This regulation involves aryl hydrocarbon receptor (AhR), a sensor of plant-derived phytochemicals, which mediates the maintenance of Retinoic acid related orphan receptor γ t-expressing innate lymphoid cells (RORγt+ ILC) in the gut and consequently formation of postnatal lymphoid follicles. Thus, AhR represents the first evidence of a molecular link between diet and immunity at intestinal mucosal surfaces.

[1]  D. Littman,et al.  Thymic origin of intestinal alphabeta T cells revealed by fate mapping of RORgammat+ cells. , 2004, Science.

[2]  Andreas Diefenbach,et al.  RORγt and commensal microflora are required for the differentiation of mucosal interleukin 22–producing NKp46+ cells , 2009, Nature Immunology.

[3]  Garet P Lahvis,et al.  Ahr null alleles: distinctive or different? , 1998, Biochemical pharmacology.

[4]  J. Lennerz,et al.  A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity , 2009, Nature.

[5]  D. Littman,et al.  Thymic Origin of Intestinal αß T Cells Revealed by Fate Mapping of RORγt+ Cells , 2004, Science.

[6]  Gérard Eberl,et al.  Lineage Relationship Analysis of RORγt+ Innate Lymphoid Cells , 2010, Science.

[7]  A. Macpherson,et al.  Adaptation of Solitary Intestinal Lymphoid Tissue in Response to Microbiota and Chemokine Receptor CCR7 Signaling1 , 2006, The Journal of Immunology.

[8]  J. Reddy,et al.  Characterization of a murine Ahr null allele: involvement of the Ah receptor in hepatic growth and development. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[9]  J. D. Di Santo,et al.  IL-7 and IL-15 independently program the differentiation of intestinal CD3−NKp46+ cell subsets from Id2-dependent precursors , 2010, The Journal of experimental medicine.

[10]  Brock Chittim,et al.  Comparative toxicogenomic analysis of the hepatotoxic effects of TCDD in Sprague Dawley rats and C57BL/6 mice. , 2006, Toxicological sciences : an official journal of the Society of Toxicology.

[11]  I. Weissman,et al.  Developing lymph nodes collect CD4+CD3- LTbeta+ cells that can differentiate to APC, NK cells, and follicular cells but not T or B cells. , 1997, Immunity.

[12]  M. Denison,et al.  Activation of the aryl hydrocarbon receptor by structurally diverse exogenous and endogenous chemicals. , 2003, Annual review of pharmacology and toxicology.

[13]  Shinichiro Sawa,et al.  Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense. , 2008, Immunity.

[14]  A. Rizzo,et al.  Aryl hydrocarbon receptor-induced signals up-regulate IL-22 production and inhibit inflammation in the gastrointestinal tract. , 2011, Gastroenterology.

[15]  S. Falkow,et al.  The eae gene of Citrobacter freundii biotype 4280 is necessary for colonization in transmissible murine colonic hyperplasia , 1993, Infection and immunity.

[16]  H. Rodewald,et al.  Kit Ligand and Il7 Differentially Regulate Peyer’s Patch and Lymph Node Development , 2010, The Journal of Immunology.

[17]  C. Garlanda,et al.  AHR drives the development of gut ILC22 cells and postnatal lymphoid tissues via pathways dependent on and independent of Notch , 2011, Nature Immunology.

[18]  M. Si-Tahar,et al.  Microbiota-induced tertiary lymphoid tissues aggravate inflammatory disease in the absence of RORγt and LTi cells , 2011, The Journal of experimental medicine.

[19]  K. Ikuta,et al.  Progenitors Deve lop , 2003 .

[20]  Emily A. Stevens,et al.  The aryl hydrocarbon receptor: a perspective on potential roles in the immune system , 2009, Immunology.

[21]  Christopher A Bradfield,et al.  The search for endogenous activators of the aryl hydrocarbon receptor. , 2008, Chemical research in toxicology.

[22]  Kenji Nakamura,et al.  Loss of teratogenic response to 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) in mice lacking the Ah (dioxin) receptor , 1997, Genes to cells : devoted to molecular & cellular mechanisms.

[23]  B. Stockinger,et al.  The aryl hydrocarbon receptor in immunity. , 2009, Trends in immunology.

[24]  Liang Zhou,et al.  The aryl hydrocarbon receptor regulates gut immunity through modulation of innate lymphoid cells. , 2012, Immunity.

[25]  Natalie A. Roberts,et al.  Exogenous Stimuli Maintain Intraepithelial Lymphocytes via Aryl Hydrocarbon Receptor Activation , 2011, Cell.

[26]  A. Cumano,et al.  Notch signaling is necessary for adult, but not fetal, development of RORγt+ innate lymphoid cells , 2011, Nature Immunology.

[27]  S. Falkow,et al.  Attaching and effacing locus of a Citrobacter freundii biotype that causes transmissible murine colonic hyperplasia , 1993, Infection and immunity.

[28]  T. Zacharewski,et al.  Integration of Genome-Wide Computation DRE Search, AhR ChIP-chip and Gene Expression Analyses of TCDD-Elicited Responses in the Mouse Liver , 2011, BMC Genomics.

[29]  C. Esser The immune phenotype of AhR null mouse mutants: not a simple mirror of xenobiotic receptor over-activation. , 2009, Biochemical pharmacology.

[30]  M. Wright Immune system impairment and hepatic fibrosis in mice lacking the dioxin-binding Ah receptor. , 1996, Human & experimental toxicology.

[31]  E. Hobeika,et al.  Natural Aryl Hydrocarbon Receptor Ligands Control Organogenesis of Intestinal Lymphoid Follicles , 2011, Science.

[32]  E. Levy,et al.  Dietary patterns and risk for Crohn's disease in children , 2008, Inflammatory bowel diseases.

[33]  J. Banchereau,et al.  Influence of the transcription factor RORγt on the development of NKp46+ cell populations in gut and skin , 2009, Nature Immunology.

[34]  Hergen Spits,et al.  Innate lymphoid cells: emerging insights in development, lineage relationships, and function. , 2012, Annual review of immunology.

[35]  D. Artis,et al.  CD4(+) lymphoid tissue-inducer cells promote innate immunity in the gut. , 2011, Immunity.

[36]  U. Pannicke,et al.  Regulated expression of nuclear receptor RORγt confers distinct functional fates to NK cell receptor-expressing RORγt(+) innate lymphocytes. , 2010, Immunity.

[37]  J. Buer,et al.  The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins , 2008, Nature.

[38]  A. Diefenbach,et al.  Control of epithelial cell function by interleukin‐22‐producing RORγt+ innate lymphoid cells , 2011, Immunology.

[39]  M. Caligiuri,et al.  Interleukin-1beta selectively expands and sustains interleukin-22+ immature human natural killer cells in secondary lymphoid tissue. , 2010, Immunity.

[40]  R. Arsenescu,et al.  Role of the xenobiotic receptor in inflammatory bowel disease , 2011, Inflammatory bowel diseases.

[41]  S. Sa,et al.  Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens , 2008, Nature Medicine.