title: Aryl hydrocarbon receptor promotes RORγt⁺ group 3 ILCs and controls intestinal immunity and inflammation.
abstract: Unlike adaptive immune cells that require antigen recognition and functional maturation during infection, innate lymphoid cells (ILCs) usually respond to pathogens promptly and serve as the first line of defense in infectious diseases. RAR-related orphan receptor (RORγt)⁺ group 3 ILCs are one of the innate cell populations that have recently been intensively studied. During the fetal stage of development, RORγt⁺ group 3 ILCs (e.g., lymphoid tissue inducer cells) are required for lymphoid organogenesis. In adult mice, RORγt⁺ group 3 ILCs are abundantly present in the gut to exert immune defensive functions. Under certain circumstances, however, RORγt⁺ group 3 ILCs can be pathogenic and contribute to intestinal inflammation. Aryl hydrocarbon receptor (Ahr), a ligand-dependent transcriptional factor, is widely expressed by various immune and non-immune cells. In the gut, the ligand for Ahr can be derived/generated from diet, microflora, and/or host cells. Ahr has been shown to regulate different cell populations in the immune system including RORγt⁺ group 3 ILCs, T helper (Th)17/22 cells, γδT cells, regulatory T cells (Tregs), Tr1 cells, and antigen presenting cells. In this review, we will focus on the development and function of RORγt⁺ group 3 ILCs, and discuss the role of Ahr in intestinal immunity and inflammation in mice and in humans. A better understanding of the function of Ahr in the gut is important for developing new therapeutic means to target Ahr in future treatment of infectious and autoimmune diseases.
authors: Department of Pathology, Feinberg School of Medicine, Northwestern University, 300 E. Superior Street, Chicago, IL, 60611, USA.
authors: Ju
authors: J
authors: Qiu
authors: Liang
authors: L
authors: Zhou
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D003092:Colitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000276:immunology* / Q000382:microbiology; D008024:Ligands; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D064307:Microbiota; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D008024:Ligands; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018336:Receptors, Aryl Hydrocarbon
references: Immunity. 2012 Oct 19;37(4):589-91
references: 23084352
references: Gut. 2008 Dec;57(12):1682-9
references: 18653729
references: Nat Immunol. 2009 Jun;10(6):603-9
references: 19448631
references: Science. 2010 Oct 29;330(6004):665-9
references: 20929731
references: Immunity. 2005 Jun;22(6):705-16
references: 15963785
references: J Immunol. 2011 Feb 1;186(3):1450-7
references: 21178013
references: Immunity. 1998 Dec;9(6):797-806
references: 9881970
references: Immunity. 2010 Jun 25;32(6):803-14
references: 20620944
references: J Immunol. 2001 Jun 1;166(11):6593-601
references: 11359812
references: Nature. 2004 Dec 23;432(7020):1040-5
references: 15616565
references: J Immunol. 2003 Nov 15;171(10):5507-13
references: 14607957
references: Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):19961-6
references: 21041655
references: Annu Rev Pharmacol Toxicol. 2000;40:519-61
references: 10836146
references: Cell. 2012 Oct 12;151(2):289-303
references: 23021777
references: Immunity. 2008 Dec 19;29(6):947-57
references: 19100701
references: J Immunol. 2012 Mar 1;188(5):2410-8
references: 22266282
references: J Exp Med. 2007 Jun 11;204(6):1267-72
references: 17502664
references: Nature. 2010 Apr 29;464(7293):1367-70
references: 20200518
references: Immunity. 2010 Nov 24;33(5):736-51
references: 21093318
references: Cell Host Microbe. 2008 Oct 16;4(4):337-49
references: 18854238
references: Eur J Immunol. 1992 Feb;22(2):329-34
references: 1347010
references: Nature. 2010 Apr 29;464(7293):1371-5
references: 20393462
references: Immunity. 2012 Sep 21;37(3):463-74
references: 22981535
references: Am J Pathol. 2011 Apr;178(4):1556-67
references: 21406171
references: Gastroenterology. 2005 Sep;129(3):969-84
references: 16143135
references: Nat Med. 2008 Mar;14(3):282-9
references: 18264109
references: Nat Immunol. 2011 Jan;12(1):21-7
references: 21113163
references: Immunity. 2012 Dec 14;37(6):1061-75
references: 23200827
references: Nature. 1999 Feb 25;397(6721):702-6
references: 10067894
references: Chem Res Toxicol. 2008 Jan;21(1):102-16
references: 18076143
references: J Exp Med. 2011 Oct 24;208(11):2321-33
references: 22006976
references: Biochim Biophys Acta. 2003 Feb 17;1619(3):263-8
references: 12573486
references: Immunity. 2012 Jan 27;36(1):92-104
references: 22177117
references: Microbes Infect. 2010 Mar;12(3):218-26
references: 20034589
references: Cell. 2011 Oct 28;147(3):629-40
references: 21999944
references: J Clin Invest. 2008 Jun;118(6):2269-80
references: 18497880
references: Nat Immunol. 2011 Sep 11;12(11):1055-62
references: 21909091
references: Cell. 2007 Oct 5;131(1):33-45
references: 17923086
references: J Exp Med. 2009 Jul 6;206(7):1465-72
references: 19564350
references: Science. 2011 Oct 14;334(6053):255-8
references: 21998396
references: Proc Natl Acad Sci U S A. 2010 Mar 23;107(12):5540-4
references: 20212110
references: J Exp Med. 2011 May 9;208(5):1027-40
references: 21518800
references: Nature. 1988 Jun 30;333(6176):855-8
references: 2968521
references: Nature. 2008 May 1;453(7191):65-71
references: 18362915
references: Nature. 2012 Nov 8;491(7423):254-8
references: 23034650
references: Nature. 2008 Nov 27;456(7221):507-10
references: 18987631
references: Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):15064-9
references: 18806221
references: J Immunol. 2007 May 1;178(9):5973-81
references: 17442982
references: Cell Host Microbe. 2012 Oct 18;12(4):445-57
references: 23084914
references: J Exp Med. 2008 Jan 21;205(1):245-56
references: 18195075
references: Gastroenterology. 2010 Sep;139(3):882-92, 892.e1-3
references: 20638936
references: Immunity. 2010 Nov 24;33(5):752-64
references: 21055975
references: Immunol Cell Biol. 2010 Aug;88(6):685-9
references: 20231854
references: Immunity. 2010 Mar 26;32(3):403-13
references: 20226692
references: J Immunol. 2009 Aug 15;183(4):2217-21
references: 19635901
references: Immunity. 2011 Jan 28;34(1):122-34
references: 21194981
references: Immunity. 2007 May;26(5):643-54
references: 17521585
references: Science. 2012 Jun 8;336(6086):1321-5
references: 22674331
references: Nat Immunol. 2010 Sep;11(9):846-53
references: 20676092
references: Nat Immunol. 2009 Aug;10(8):857-63
references: 19578369
references: Nat Rev Immunol. 2012 Oct;12(10):696-708
references: 23007570
references: Nat Rev Immunol. 2002 May;2(5):336-45
references: 12033739
references: Annu Rev Immunol. 1999;17:399-433
references: 10358764
references: PLoS One. 2011;6(8):e23522
references: 21858153
references: Mucosal Immunol. 2013 Jan;6(1):177-88
references: 22854708
references: Nat Immunol. 2009 Jan;10(1):75-82
references: 19029904
references: Gastroenterology. 2004 Nov;127(5):1463-73
references: 15521015
references: Cell. 1994 Oct 7;79(1):143-56
references: 7923373
references: Dig Dis Sci. 2011 Sep;56(9):2532-44
references: 21374063
references: Clin Exp Immunol. 2010 Jun;160(3):440-9
references: 20148914
references: J Immunol. 2004 Jul 15;173(2):1390-8
references: 15240735
references: Immunity. 2012 Oct 19;37(4):634-48
references: 23063333
references: Am J Physiol Gastrointest Liver Physiol. 2006 Apr;290(4):G827-38
references: 16537974
references: Cell. 2009 Apr 17;137(2):216-33
references: 19379690
references: Immunity. 2012 Aug 24;37(2):339-50
references: 22921121
references: J Immunol. 2005 Dec 1;175(11):7348-56
references: 16301641
references: J Exp Med. 2010 Feb 15;207(2):273-80
references: 20142427
references: Immunity. 2008 Jan;28(1):29-39
references: 18164222
references: Nat Immunol. 2009 Aug;10(8):864-71
references: 19578368
references: Nat Immunol. 2011 Nov 20;13(2):144-51
references: 22101730
references: J Immunol. 2006 Jul 1;177(1):566-73
references: 16785554
references: Nature. 2000 Jul 20;406(6793):309-14
references: 10917533
references: Nat Immunol. 2011 Sep 11;12(10):949-58
references: 21909092
references: Nat Immunol. 2008 Jun;9(6):667-75
references: 18425132
references: Annu Rev Immunol. 2012;30:647-75
references: 22224763
references: EMBO J. 2011 Jun 17;30(14):2934-47
references: 21685873
references: Gastroenterology. 2011 Jul;141(1):237-48, 248.e1
references: 21600206
references: Nat Immunol. 2011 Apr;12(4):312-9
references: 21297643
references: Immunity. 1996 Dec;5(6):537-49
references: 8986714
references: J Exp Med. 2007 May 14;204(5):1119-30
references: 17452521
references: Nat Immunol. 2012 Jan 22;13(3):229-36
references: 22267218
references: Toxicol Sci. 2011 Mar;120(1):68-78
references: 21131560
references: Cell Host Microbe. 2011 Jul 21;10(1):44-53
references: 21767811
references: Science. 2011 Dec 16;334(6062):1561-5
references: 22033518
references: J Exp Med. 2011 Jun 6;208(6):1127-33
references: 21576383
references: Nat Immunol. 2010 Oct;11(10):945-52
references: 20818394
references: J Exp Med. 2012 Feb 13;209(2):251-8
references: 22291094
references: Immunity. 2012 Oct 19;37(4):674-84
references: 23063332
references: Immunity. 2002 Sep;17(3):363-73
references: 12354388
references: J Exp Med. 2009 Aug 31;206(9):2027-35
references: 19703987
references: Immunity. 2004 Aug;21(2):241-54
references: 15308104
references: J Exp Med. 2009 Jan 16;206(1):35-41
references: 19114665
references: Nature. 2009 Feb 5;457(7230):722-5
references: 18978771
references: J Exp Med. 2006 Oct 2;203(10):2271-9
references: 16982811
references: Nucleic Acids Res. 2003 Aug 15;31(16):4717-28
references: 12907712
references: Immunol Rev. 2003 Oct;195:81-90
references: 12969312
references: Immunol Rev. 2007 Feb;215:103-13
references: 17291282
references: Inflamm Bowel Dis. 2008 Feb;14(2):204-12
references: 18022867
references: J Immunol. 2008 Nov 1;181(9):6265-74
references: 18941217
references: Nature. 2008 May 1;453(7191):106-9
references: 18362914
references: Nat Immunol. 2010 Sep;11(9):854-61
references: 20676095
references: Immunity. 2012 Feb 24;36(2):276-87
references: 22306017
references: Mucosal Immunol. 2010 Jul;3(4):361-73
references: 20445503
references: Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7451-5
references: 10377435
references: Biochem Pharmacol. 1998 Apr 15;55(8):1155-62
references: 9719469
references: Immunity. 2010 Jun 25;32(6):815-27
references: 20620945
references: Nat Immunol. 2004 Jan;5(1):64-73
references: 14691482
references: J Exp Med. 2012 Apr 9;209(4):729-40
references: 22430492
references: Curr Opin Immunol. 2000 Apr;12(2):166-72
references: 10712939
references: Science. 2008 Feb 8;319(5864):822-5
references: 18258917
references: Eur J Immunol. 2001 Apr;31(4):980-8
references: 11298322
references: Nat Med. 2004 Mar;10(3):299-304
references: 14966519
references: J Exp Med. 2011 Jan 17;208(1):125-34
references: 21173107
references: J Biol Chem. 1996 Feb 16;271(7):3743-9
references: 8631989
references: Cell. 1996 Jan 26;84(2):321-30
references: 8565077
references: Nature. 2011 Jun 15;474(7351):307-17
references: 21677747
references: Int Immunol. 1998 Jan;10(1):1-6
references: 9488150
references: Immunity. 2008 Dec 19;29(6):958-70
references: 19084435
references: Gut. 2009 Dec;58(12):1629-36
references: 19740775
references: Nat Immunol. 2009 Jan;10(1):83-91
references: 19029903
references: Immunity. 1997 Oct;7(4):493-504
references: 9354470
references: J Immunol. 2010 Jul 15;185(2):1177-85
references: 20566828
references: Drug Metab Dispos. 1998 Dec;26(12):1194-8
references: 9860927
references: Nat Immunol. 2009 Jan;10(1):66-74
references: 19029905
references: J Exp Med. 2012 Aug 27;209(9):1595-609
references: 22891275
references: Nat Immunol. 2011 Apr;12(4):320-6
references: 21336274
references: J Exp Med. 2009 Sep 28;206(10):2271-84
references: 19752184
references: Cell. 2006 Sep 22;126(6):1121-33
references: 16990136