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

Lymphoid Tissue Development Unit, Department of Immunology, Institut Pasteur, 75724 Paris, France.
The Journal of Immunology (Impact Factor: 4.92). 02/2011; 186(3):1531-7. DOI: 10.4049/jimmunol.1001723
Source: PubMed


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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Available from: Matthias Lochner, Mar 31, 2014
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    • "Induction of Th17 cytokines requires ligation of the TCR, but the specificity of lamina propria Th17 cells does not appear to be restricted to microbial antigen. Mice with monospecific T cells have intestinal Th17 cells and monoassociation of mice with SFB results in as many Th17 cells as in mice with a broad spectrum of intestinal microbes (Ivanov et al., 2009; Lochner et al., 2011). Th17 cells may therefore be in large part selfreactive T cells circulating through the lamina propria, where a reduced threshold for TCR signaling and the presence of appropriate cytokines results in their polarization. "
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    • "However, even though SFB is an efficient inducer of Th17 cells, it also efficiently induces other types of T helper cells (Gaboriau-Routhiau et al., 2009) and the production of IgA (Talham et al., 1999). Furthermore, other types of bacteria can induce Th17 cells (Gaboriau- Routhiau et al., 2009; Lochner et al., 2011a), and the impact of an SFB-less complex microbiota on autoimmune disease progression remains to be assessed. Thus, even though Th17 cells are associated with proinflammatory pathology, we believe that this 'function' is associated with a particular context or genetic susceptibility of the host. "
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