title: Restricted microbiota and absence of cognate TCR antigen leads to an unbalanced generation of Th17 cells.
abstract: Retinoic acid-related orphan receptor (ROR)γt(+) TCRαβ(+) cells expressing IL-17, termed Th17 cells, are most abundant in the intestinal lamina propria. Symbiotic microbiota are required for the generation of Th17 cells, but the requirement for microbiota-derived Ag is not documented. In this study, we show that normal numbers of Th17 cells develop in the intestine of mice that express a single TCR in the absence of cognate Ag, whereas the microbiota remains essential for their development. However, such mice, or mice monocolonized with the Th17-inducing segmented filamentous bacteria, fail to induce normal numbers of Foxp3(+) RORγt(+) T cells, the regulatory counterpart of IL-17(+)RORγt(+) T cells. These results demonstrate that a complex microbiota and cognate Ag are required to generate a properly regulated set of RORγt(+) T cells and Th17 cells.
authors.affiliation: Lymphoid Tissue Development Unit, Department of Immunology, Institut Pasteur, 75724 Paris, France.
authors.forename: Matthias
authors.initials: M
authors.lastname: Lochner
authors.forename: Marion
authors.initials: M
authors.lastname: Bérard
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Sawa
authors.forename: Siona
authors.initials: S
authors.lastname: Hauer
authors.forename: Valérie
authors.initials: V
authors.lastname: Gaboriau-Routhiau
authors.forename: Tahia Diana
authors.initials: TD
authors.lastname: Fernandez
authors.forename: Johannes
authors.initials: J
authors.lastname: Snel
authors.forename: Philippe
authors.initials: P
authors.lastname: Bousso
authors.forename: Nadine
authors.initials: N
authors.lastname: Cerf-Bensussan
authors.forename: Gérard
authors.initials: G
authors.lastname: Eberl
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018791:CD4 Lymphocyte Count; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D005856:Germ-Free Life / Q000235:genetics / Q000276:immunology; D016908:Gram-Positive Bacterial Infections / Q000276:immunology / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; D011948:Receptors, Antigen, T-Cell; C539901:Rorc protein, mouse; D049452:Green Fluorescent Proteins