Restricted Microbiota and Absence of Cognate TCR Antigen Leads to an Unbalanced Generation of Th17 Cells.
2011
Lochner, Matthias | Bérard, Marion | Sawa, Shinichiro | Hauer, Siona | Gaboriau-Routhiau, Valérie | Fernandez, Tahia Diana | Snel, Johannes | Bousso, Philippe | Cerf-Bensussan, Nadine | Eberl, Gérard | Développement des Tissus Lymphoïdes ; Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS) | Institute of infection immunolog (TWINCORE) ; Centre for experimental and clinical infection research | Animalerie centrale (Plate-forme) ; Institut Pasteur [Paris] (IP) | Institute of infection immunology (TWINCORE) ; Centre for experimental and clinical infection research | Interactions de l'épithelium intestinal et du système immunitaire (UMR_S 793) ; Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM) | MICrobiologie de l'ALImentation au Service de la Santé (MICALIS) ; Institut National de la Recherche Agronomique (INRA)-AgroParisTech | Biologie des Populations Lymphocytaires ; Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS) | NIZO [Ede, Netherlands] | Dynamiques des Réponses Immunes ; Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM) | Institut Pasteur; Maine de Paris; Agence Nationale de la Recherche; European Commission; Deutsche Forschungsgemeinschaft; Schlumberger Foundation; Hanover Medical School
International audience
显示更多 [+] 显示较少 [-]英语. 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.
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