Restricted Microbiota and Absence of Cognate TCR Antigen Leads to an Unbalanced Generation of Th17 Cells.

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Lochner, Matthias | Bérard, Marion | Sawa, Shinichiro | Hauer, Siona | Gaboriau-Routhiau, Valérie | Fernandez, Tahia Diana | Snel, Johannes | Bousso, Philippe | Cerf-Bensussan, Nadine | Eberl, Gérard

Edité par CCSD ; Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists -

International audience. 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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