Redundant cytokine requirement for intestinal microbiota-induced Th17 cell differentiation in draining lymph nodes
Teruyuki Sano, Takahiro Kageyama, Victoria Fang, Ranit Kedmi, Carlos Serafin Martinez, Jhimmy Talbot, Alessandra Chen, Ivan Cabrera, Oleksandra Gorshko, Reina Kurakake, Yi Yang, Charles Ng, Susan R. Schwab, Dan R. Littman
Abstract
Differentiation of intestinal T helper 17 (Th17) cells, which contribute to mucosal barrier protection from invasive pathogens, is dependent on colonization with distinct commensal bacteria. Segmented filamentous bacteria (SFB) are sufficient to support Th17 cell differentiation in mouse, but the molecular and cellular requirements for this process remain incompletely characterized. Here, we show that intestine-draining mesenteric lymph nodes (MLNs), not intestine proper, are the dominant site of SFB-induced intestinal Th17 cell differentiation. Subsequent migration of these cells to the intestinal lamina propria is dependent on their upregulation of integrin β7. Stat3-dependent induction of RORγt, the Th17 cell-specifying transcription factor, largely depends on IL-6, but signaling through the receptors for IL-21 and IL-23 can compensate for absence of IL-6 to promote SFB-directed Th17 cell differentiation. These results indicate that redundant cytokine signals guide commensal microbe-dependent Th17 cell differentiation in the MLNs and accumulation of the cells in the lamina propria.