Antigen-Specific Development of Mucosal Foxp3+RORγt+ T Cells from Regulatory T Cell Precursors.
Foxp3+retinoic acid-related orphan receptor (ROR)γt+T cells have recently been characterized as an immunoregulatory population highly enriched in the colon lamina propria. However, their developmental origin and relationship to RORγt-regulatory T and Th17 cells remain unclear. In this study, we use a fixed TCRβ system to show that the TCR repertoire of the Foxp3+RORγt+population is mostly distinct compared with other colonic T cell subsets. However, of these TCRs, a fraction is also found in the Th17 subset, suggesting that TCR repertoire overlap may contribute to the reported ability of Foxp3+RORγt+cells to regulate Th17 immunity. Naive transgenic T cells expressing a Foxp3+RORγt+-restricted TCR first acquire a Foxp3+RORγt-phenotype before coexpressing RORγt, suggesting that Foxp3+RORγt+cell development can occur via an RORγt-regulatory T cell intermediate.
Division of Rheumatology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Benjamin D
0000-0003-1009-7312
BD
Solomon
Division of Rheumatology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110 chsieh@wustl.edu.
Chyi-Song
CS
Hsieh
D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism*; D054504:Precursor Cells, T-Lymphoid / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D016693:Receptors, Antigen, T-Cell, alpha-beta
Nature. 2008 May 8;453(7192):236-40
18368049
Ecology. 2012 Dec;93(12):2533-47
23431585
Nat Immunol. 2013 Sep;14 (9):937-48
23913046
Genesis. 2006 Jan;44(1):29-33
16397869
J Leukoc Biol. 2000 Oct;68(4):568-74
11037980
Science. 2015 Aug 28;349(6251):993-7
26272906
Science. 2015 Aug 28;349(6251):989-93
26160380
Nat Immunol. 2009 Jun;10(6):610-7
19430476
Immunity. 2013 Jun 27;38(6):1261-70
23791647
J Exp Med. 2008 Jun 9;205(6):1381-93
18504307
J Immunol. 2011 Feb 1;186(3):1531-7
21178008
Immunity. 2012 Sep 21;37(3):475-86
22921379
Immunity. 2007 Sep;27(3):493-504
17869133
Cell. 2009 Oct 30;139(3):485-98
19836068
Genome Med. 2015 May 28;7(1):49
26140055
Nature. 2013 Feb 7;494(7435):116-20
23334413
Nat Rev Immunol. 2014 Oct;14(10):667-85
25234148
Nature. 2009 Mar 19;458(7236):351-6
19182775
J Exp Med. 2007 Aug 6;204(8):1757-64
17620361
Cell Rep. 2016 Sep 27;17(1):206-20
27681432
Nature. 2013 Aug 8;500(7461):232-6
23842501
Nat Immunol. 2006 Apr;7(4):401-10
16532000
Eur J Immunol. 2015 May;45(5):1524-34
25726757
Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11903-8
18695219
Annu Rev Immunol. 2012;30:531-64
22224781
Nucleic Acids Res. 2003 Jan 1;31(1):307-10
12520009
Proc Natl Acad Sci U S A. 2007 Aug 21;104(34):13780-5
17699621
Mucosal Immunol. 2016 Mar;9(2):444-57
26307665
Nature. 2011 Sep 21;478(7368):250-4
21937990
Cell Rep. 2015 Aug 25;12(8):1314-24
26279572
Nat Immunol. 2009 Jun;10(6):595-602
19412181