MUCOSAL IMMUNOLOGY. Individual intestinal symbionts induce a distinct population of RORγ⁺ regulatory T cells.
T regulatory cells that express the transcription factor Foxp3 (Foxp3(+) T(regs)) promote tissue homeostasis in several settings. We now report that symbiotic members of the human gut microbiota induce a distinct T(reg) population in the mouse colon, which constrains immuno-inflammatory responses. This induction—which we find to map to a broad, but specific, array of individual bacterial species—requires the transcription factor Rorγ, paradoxically, in that Rorγ is thought to antagonize FoxP3 and to promote T helper 17 (T(H)17) cell differentiation. Rorγ's transcriptional footprint differs in colonic T(regs) and T(H)17 cells and controls important effector molecules. Rorγ, and the T(regs) that express it, contribute substantially to regulating colonic T(H)1/T(H)17 inflammation. Thus, the marked context-specificity of Rorγ results in very different outcomes even in closely related cell types.
Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston 02115, MA, USA.
Esen
E
Sefik
Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston 02115, MA, USA.
Naama
N
Geva-Zatorsky
Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston 02115, MA, USA.
Sungwhan
S
Oh
Division of Gastroenterology and Hepatology, Brigham and Women's Hospital, Boston, MA 02115, USA, and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Liza
L
Konnikova
Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston 02115, MA, USA.
David
D
Zemmour
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Abigail Manson
AM
McGuire
Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston 02115, MA, USA.
Dalia
D
Burzyn
Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston 02115, MA, USA.
Adriana
A
Ortiz-Lopez
Tempero Pharmaceuticals, a GSK Company, Cambridge, MA 02115, USA.
Mercedes
M
Lobera
Tempero Pharmaceuticals, a GSK Company, Cambridge, MA 02115, USA.
Jianfei
J
Yang
Tempero Pharmaceuticals, a GSK Company, Cambridge, MA 02115, USA.
Shomir
S
Ghosh
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Ashlee
A
Earl
Division of Gastroenterology and Hepatology, Brigham and Women's Hospital, Boston, MA 02115, USA, and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Scott B
SB
Snapper
UCB Pharma, Slough, Berkshire, UK.
Ray
R
Jupp
Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston 02115, MA, USA.
Dennis
D
Kasper
Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston 02115, MA, USA. Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA. cbdm@hms.harvard.edu.
Diane
D
Mathis
Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston 02115, MA, USA. Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA. cbdm@hms.harvard.edu.
Christophe
C
Benoist
D000818:Animals; D001419:Bacteria / Q000276:immunology; D041963:Bacteroidetes / Q000276:immunology / Q000502:physiology; D003093:Colitis, Ulcerative / Q000276:immunology; D003106:Colon / Q000276:immunology* / Q000382:microbiology; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D018928:Immunity, Mucosal; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000276:immunology* / Q000502:physiology; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism*; D013559:Symbiosis; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology; D014158:Transcription, Genetic; D059467:Transcriptome
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; C539901:Rorc protein, mouse