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Publication : Redundant cytokine requirement for intestinal microbiota-induced Th17 cell differentiation in draining lymph nodes.

First Author  Sano T Year  2021
Journal  Cell Rep Volume  36
Issue  8 Pages  109608
PubMed ID  34433045 Mgi Jnum  J:314244
Mgi Id  MGI:6765719 Doi  10.1016/j.celrep.2021.109608
Citation  Sano T, et al. (2021) Redundant cytokine requirement for intestinal microbiota-induced Th17 cell differentiation in draining lymph nodes. Cell Rep 36(8):109608
abstractText  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 beta7. Stat3-dependent induction of RORgammat, 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.
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