ROR?t+ APCs require a distinct cis-regulatory element to instruct tolerance to dietary antigens [RNA-seq]

ROR?t is the linage-specific transcription factor for both ILC3 and T-helper 17 (Th17) counterparts, who take an essential place in regulating intestinal homeostasis. While the biological significance of high ROR?t expression and its distinct regulatory mechanisms in ILC3s remains investigation. Through comparing ATAC-seq results on ILC3 and Th17 cells, we identified an open chromatin region (OCR369) which specifically regulates ILC3 ROR?t expression and development. Mechanistically, OCR369 is bind by the ROR?t activator RUNX3, and is also involved in the chromatin-loop formation between OCR369 and ROR?t-promoter. OCR369 depletion also impaired the MHCII+ ILC3s, a group of antigen-presenting cells that regulate ROR?t+ Treg cells. And disruption of Th/ Treg balance in the OCR369-deficient mice leads to the spontaneous type 2 inflammation in the small intestine, and impaired generation of oral tolerance. Thus, our study revealed a specific ROR?t amplifying mechanism in ILC3 and its important role in maintaining intestinal immune environment and food tolerance. Overall design: About 0.5 cm length of small intestine was cut at ~10 cm to the cecum from naïve 20 weeks old littermates (n=3), extracted RNA using TRIzol reagent (Invitrogen, 15596026CN).Gene expression profiles were compared btween the Rorc ?369 and Rorc WT mice